question_id
stringlengths 24
24
| question
stringlengths 13
215
| answer
stringlengths 2
3.15k
| relevant_passage_ids
sequencelengths 1
157
| type
stringclasses 4
values | snippets
listlengths 1
121
|
|---|---|---|---|---|---|
532c169ed6d3ac6a3400001f | Are there plasma membrane receptors for thyroid hormones? | Receptors for thyroid hormones are present on plasma membrane of cells; in particular thyroid hormones bind integrin that is a heterodimeric component of plasma membrane | [
"11117200",
"22986150",
"20658515",
"24113777",
"6290538",
"22945636",
"169249",
"18329679",
"227209",
"23137442",
"20232113",
"23926648",
"19900468",
"22414628",
"6093898",
"17570630",
"23021374",
"20051527",
"12165107",
"17983645",
"2534509",
"23943159",
"8936679",
"1747413",
"6312037",
"19755667"
] | yesno | [
{
"offsetInBeginSection": 1,
"offsetInEndSection": 150,
"text": "ntegrins are heterodimeric structural components of the plasma membrane whose ligands include a large number of extracellular matrix (ECM) proteins. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23943159",
"endSection": "abstract"
},
{
"offsetInBeginSection": 405,
"offsetInEndSection": 660,
"text": "Recently, integrin αvβ3 has been shown to have a panel of previously unappreciated small molecule receptor sites for thyroid hormone and hormone analogues, for dihydrotestosterone, and for resveratrol, a polyphenol that has certain estrogen-like features.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23943159",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1541,
"offsetInEndSection": 1666,
"text": "The integrin receptor activation by T4 may take a role in plasma membrane processes involved in the male reproductive system.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23137442",
"endSection": "abstract"
},
{
"offsetInBeginSection": 665,
"offsetInEndSection": 839,
"text": "Rapid signaling via this plasma membrane binding site appears to be responsible for many nongenomic effects of thyroid hormones, independent of the classic nuclear receptors.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22414628",
"endSection": "abstract"
}
] |
56c1f020ef6e394741000047 | Which disorder is rated by Palmini classification? | Palmini classification system is used for classification of focal cortical dysplasia. | [
"25219355",
"21275980",
"23667118",
"24743217",
"17535679",
"22642611",
"25296541",
"23899121",
"25601060",
"20618424",
"22844307",
"23551067",
"24649461",
"15965699",
"22510082"
] | factoid | [
{
"offsetInBeginSection": 407,
"offsetInEndSection": 584,
"text": "This study also provides an opportunity to compare the predictive value of the ILAE and Palmini et al classification schemes with regard to the type I focal cortical dysplasias.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1242,
"offsetInEndSection": 1492,
"text": "Of the 91 patients, there were 50 patients with ILAE focal cortical dysplasia type Ib, 41 with ILAE focal cortical dysplasia type Ic, 63 with Palmini et al focal cortical dysplasia type IA, and 28 with Palmini et al focal cortical dysplasia type IB. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1544,
"offsetInEndSection": 2066,
"text": "Crude analysis revealed no significant difference between patients with subtypes of ILAE focal cortical dysplasia type I or Palmini et al focal cortical dysplasia type I concerning postoperative outcome according to the Engel and ILAE scoring systems on seizure frequency. Our findings revealed no significant difference concerning surgical outcome with respect to seizure frequency for the histologic subtypes of ILAE focal cortical dysplasia type I (Ib vs Ic) or Palmini et al focal cortical dysplasia type I (IA vs IB).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217",
"endSection": "abstract"
},
{
"offsetInBeginSection": 868,
"offsetInEndSection": 1100,
"text": "MCD were classified following the existing classification schemes (Barkovich et al., 2012. Brain. 135, 1348-1369; Palmini et al., 2004. Neurology. 62, S2-S8) and the ILAE classification for FCD recently proposed by Blümcke in 2011. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25219355",
"endSection": "abstract"
},
{
"offsetInBeginSection": 601,
"offsetInEndSection": 1035,
"text": "DISCUSSION: This short review provides an overview of the issues which account for the varied historical approaches to FCD classification and descriptions of gross pathologic findings associated with FCD and an overview of two more recently developed and widely used schema, the Palmini et al. (Neurology 62: S2-8, 2004) and the International League Against Epilepsy (ILAE) classifications Blumcke et al. Epilepsia 52: 158-174, 2011. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25296541",
"endSection": "abstract"
},
{
"offsetInBeginSection": 235,
"offsetInEndSection": 449,
"text": " In contrast to the former FCD classification by Palmini, which considered only histologic features, the novel ILAE classification also relies on magnetic resonance imaging (MRI) findings and presumed pathogenesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23551067",
"endSection": "abstract"
},
{
"offsetInBeginSection": 590,
"offsetInEndSection": 761,
"text": "Rates of high frequency oscillations in patients with pathologically confirmed focal cortical dysplasia of Palmini type 1a and b were compared with those in type 2a and b.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23899121",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 223,
"text": "Tuberous sclerosis complex (TSC) and severe cortical dysplasia (CD), or CD type II according to Palmini classification, share histopathologic similarities, specifically the presence of cytomegalic neurons and balloon cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20618424",
"endSection": "abstract"
},
{
"offsetInBeginSection": 581,
"offsetInEndSection": 758,
"text": "This study also provides an opportunity to compare the predictive value of the ILAE and Palmini et al classification schemes with regard to the type I focal cortical dysplasias.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1192,
"offsetInEndSection": 1446,
"text": "Ten of the 12 patients (83%) who had adequate tissue excised adjacent to the meningioangiomatosis demonstrated evidence of focal cortical dysplasia, with 6 of those (60%) classified as Palmini type IA, and 4 patients (40%) classified as Palmini type IIA.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25601060",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1483,
"offsetInEndSection": 1732,
"text": "Of the 91 patients, there were 50 patients with ILAE focal cortical dysplasia type Ib, 41 with ILAE focal cortical dysplasia type Ic, 63 with Palmini et al focal cortical dysplasia type IA, and 28 with Palmini et al focal cortical dysplasia type IB.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2055,
"offsetInEndSection": 2304,
"text": "Our findings revealed no significant difference concerning surgical outcome with respect to seizure frequency for the histologic subtypes of ILAE focal cortical dysplasia type I (Ib vs Ic) or Palmini et al focal cortical dysplasia type I (IA vs IB).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1806,
"offsetInEndSection": 2078,
"text": "Crude analysis revealed no significant difference between patients with subtypes of ILAE focal cortical dysplasia type I or Palmini et al focal cortical dysplasia type I concerning postoperative outcome according to the Engel and ILAE scoring systems on seizure frequency.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1165,
"offsetInEndSection": 1471,
"text": "Since early 2000, the definition of FCD has gradually been given a broader interpretation than the case described by Taylor et al., as shown in Palmini's classification (2004) or the newest classification (2011) proposed by the Neuropathology Task Force of the International League Against Epilepsy (ILAE).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23667118",
"endSection": "abstract"
},
{
"offsetInBeginSection": 311,
"offsetInEndSection": 390,
"text": "Palmini's classification proposed in 2004 is now widely used to categorize FCD.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24649461",
"endSection": "abstract"
},
{
"offsetInBeginSection": 637,
"offsetInEndSection": 756,
"text": "According to Palmini's classification system, these lesions were categorized as focal cortical dysplasia (FCD) type II.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15965699",
"endSection": "abstract"
},
{
"offsetInBeginSection": 439,
"offsetInEndSection": 652,
"text": "In contrast to the former FCD classification by Palmini, which considered only histologic features, the novel ILAE classification also relies on magnetic resonance imaging (MRI) findings and presumed pathogenesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23551067",
"endSection": "abstract"
},
{
"offsetInBeginSection": 521,
"offsetInEndSection": 641,
"text": "According to Palmini's classification system, these lesions were categorized as focal cortical dysplasia (FCD) type II. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15965699",
"endSection": "abstract"
},
{
"offsetInBeginSection": 528,
"offsetInEndSection": 712,
"text": "According to Palmini's classification system, the following pathologic subgroups were identified: FCD type IA (3/38), FCD type IB (20/38), FCD type IIA (5/38) and FCD type IIB (5/38). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17535679",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1120,
"offsetInEndSection": 1275,
"text": "In addition, severe pathologic features (Palmini's classification, FCD type II) (p = 0.025) showed significant correlation with a better surgical outcome. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21275980",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 224,
"text": "Tuberous sclerosis complex (TSC) and severe cortical dysplasia (CD), or CD type II according to Palmini classification, share histopathologic similarities, specifically the presence of cytomegalic neurons and balloon cells. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20618424",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1135,
"offsetInEndSection": 1362,
"text": "In detail, according to Palmini's classification, mild malformations of cortical development (mMCDs) were disclosed in three patients, focal cortical dysplasia (FCD) type Ia in three patients, and FCD type Ib in five patients. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22510082",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2293,
"offsetInEndSection": 2416,
"text": "These results showed considerable improvement compared to a previous study evaluating the 2004 Palmini FCD classification. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22642611",
"endSection": "abstract"
},
{
"offsetInBeginSection": 236,
"offsetInEndSection": 450,
"text": "In contrast to the former FCD classification by Palmini, which considered only histologic features, the novel ILAE classification also relies on magnetic resonance imaging (MRI) findings and presumed pathogenesis. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23551067",
"endSection": "abstract"
},
{
"offsetInBeginSection": 591,
"offsetInEndSection": 763,
"text": "Rates of high frequency oscillations in patients with pathologically confirmed focal cortical dysplasia of Palmini type 1a and b were compared with those in type 2a and b. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23899121",
"endSection": "abstract"
},
{
"offsetInBeginSection": 945,
"offsetInEndSection": 1200,
"text": "Ten of the 12 patients (83%) who had adequate tissue excised adjacent to the meningioangiomatosis demonstrated evidence of focal cortical dysplasia, with 6 of those (60%) classified as Palmini type IA, and 4 patients (40%) classified as Palmini type IIA. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25601060",
"endSection": "abstract"
},
{
"offsetInBeginSection": 337,
"offsetInEndSection": 553,
"text": "Numerous classifications of the complex structural abnormalities of focal cortical dysplasia have been proposed - from Taylor et al. in 1971 to the last modification of Palmini classification made by Blumcke in 2011.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22844307",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 224,
"text": "Tuberous sclerosis complex (TSC) and severe cortical dysplasia (CD), or CD type II according to Palmini classification, share histopathologic similarities, specifically the presence of cytomegalic neurons and balloon cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20618424",
"endSection": "abstract"
},
{
"offsetInBeginSection": 470,
"offsetInEndSection": 860,
"text": "in 1971 to the last modification of Palmini classification made by Blumcke in 2011. In general, three types of cortical dysplasia are recognized.Type I focal cortical dysplasia with mild symptomatic expression and late onset, is more often seen in adults, with changes present in the temporal lobe.Clinical symptoms are more severe in type II of cortical dysplasia usually seen in children.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22844307",
"endSection": "abstract"
},
{
"offsetInBeginSection": 228,
"offsetInEndSection": 441,
"text": "In contrast to the former FCD classification by Palmini, which considered only histologic features, the novel ILAE classification also relies on magnetic resonance imaging (MRI) findings and presumed pathogenesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23551067",
"endSection": "abstract"
},
{
"offsetInBeginSection": 880,
"offsetInEndSection": 1276,
"text": "Since early 2000, the definition of FCD has gradually been given a broader interpretation than the case described by Taylor et al., as shown in Palmini's classification (2004) or the newest classification (2011) proposed by the Neuropathology Task Force of the International League Against Epilepsy (ILAE). The ILAE classification describes 3 types of disease: Type I, Type II, and Type III.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23667118",
"endSection": "abstract"
},
{
"offsetInBeginSection": 470,
"offsetInEndSection": 615,
"text": "in 1971 to the last modification of Palmini classification made by Blumcke in 2011. In general, three types of cortical dysplasia are recognized.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22844307",
"endSection": "abstract"
}
] |
52f4f2082059c6d71c00001d | what is the role of erythropoietin in cardiac regeneration after myocardial infarction? | In preclinical studies, erythropoietin improved cardiac function and perfusion by angiomyogenesis and protection of cardiomyocytes in myocardial infarction indicating that erythropoietin may play a role in the stimulation of cell regeneration under normal physiologic conditions and in patients with myocardial injury. Epo overexpression was found to enhance the cellular regenerative properties of MSCs by both autocrine and paracrine pathways. However, results from recent clinical trials did not support beneficial effects of cytokine therapy with erythropoietin in patients with myocardial infarction. | [
"22649318",
"17576662",
"21258568",
"16717399",
"16814664",
"18397963",
"17239026",
"22318706",
"19092364",
"23137502",
"15992646",
"17106196",
"19449462",
"22595018",
"18827024",
"18510486",
"20849606"
] | summary | [
{
"offsetInBeginSection": 1224,
"offsetInEndSection": 1377,
"text": "EPO in patients with STEMI treated with PCI is associated with an increase in diameter stenosis that is not associated with circulating progenitor cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22318706",
"endSection": "abstract"
},
{
"offsetInBeginSection": 98,
"offsetInEndSection": 322,
"text": "The cytokines granulocyte colony-stimulating factor, erythropoietin, and stem cell factor may play a role in helping to stimulate cell regeneration under normal physiologic conditions and in patients with myocardial injury. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19092364",
"endSection": "abstract"
},
{
"offsetInBeginSection": 468,
"offsetInEndSection": 807,
"text": "In preclinical study, G-CSF and erythropoietin improved cardiac function and perfusion by angiomyogenesis and protection of cardiomyocytes in myocardial infarction. However, results from recent clinical trials did not support beneficial effects of cytokine therapy with G-CSF or erythropoietin alone in patients with myocardial infarction.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18510486",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1661,
"offsetInEndSection": 1775,
"text": "Epo overexpression enhances the cellular regenerative properties of MSCs by both autocrine and paracrine pathways.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18397963",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1176,
"offsetInEndSection": 1326,
"text": "Transplantation of MSC combined with cytokine EPO is superior to either of the monotherapy approach for angiomyogenesis and cardiac function recovery.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17239026",
"endSection": "abstract"
}
] |
56b9c937ac7ad10019000001 | Does Rad9 interact with Aft1 in S.cerevisiae? | Yes. Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events. | [
"25300486"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 142,
"text": "Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486",
"endSection": "title"
},
{
"offsetInBeginSection": 186,
"offsetInEndSection": 1376,
"text": "Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ∼2% of the coding genome in the absence of exogenously induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486",
"endSection": "abstract"
},
{
"offsetInBeginSection": 186,
"offsetInEndSection": 372,
"text": "Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 141,
"text": "Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486",
"endSection": "title"
},
{
"offsetInBeginSection": 186,
"offsetInEndSection": 786,
"text": "Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ?2% of the coding genome in the absence of exogenously induced DNA damage. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486",
"endSection": "abstract"
},
{
"offsetInBeginSection": 786,
"offsetInEndSection": 1376,
"text": "Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486",
"endSection": "abstract"
}
] |
5162e011298dcd4e51000049 | Are there any desmins present in plants? | No. Desmins are type III intermediate filament (IF) proteins that have been identified to date only in metazoa (human, Danio rerio, bovine). Desmins are also associated with severe forms of skeletal, cardiac and myofibrillar myopathies. | [
"18033728",
"19026658",
"1694790",
"20171226",
"10929203",
"7460905",
"12529857",
"2659540",
"8752741"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 155,
"text": "Inherited mutations in the gene coding for the intermediate filament protein desmin have been demonstrated to cause severe skeletal and cardiac myopathies.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20171226",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 228,
"text": "Mutations in the intermediate filament (IF) protein desmin cause severe forms of myofibrillar myopathy characterized by partial aggregation of the extrasarcomeric desmin cytoskeleton and structural disorganization of myofibrils.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026658",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 135,
"offsetInEndSection": 479,
"text": "The family of 70 intermediate filament genes (including those encoding keratins, desmins, and lamins) is now known to be associated with a wide range of diverse diseases, at least 72 distinct human pathologies, including skin blistering, muscular dystrophy, cardiomyopathy, premature aging syndromes, neurodegenerative disorders, and cataract. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18033728",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 75,
"text": "Mutations in desmin have been associated with a subset of human myopathies.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12529857",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 99,
"text": "Characterization of a zebrafish (Danio rerio) desmin cDNA: an early molecular marker of myogenesis.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10929203",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 93,
"text": "Acute effects of desmin mutations on cytoskeletal and cellular integrity in cardiac myocytes.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12529857",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 293,
"text": "Desmin is a muscle-specific protein and a constitutive subunit of the intermediate filaments (IF) in skeletal, cardiac and smooth muscles. It is an early marker of skeletal muscle myogenesis. We have characterized a clone of desmin cDNA from an embryonic zebrafish (Danio rerio) cDNA library. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10929203",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1055,
"offsetInEndSection": 1246,
"text": "Immunohistochemical investigation showed a positive reaction for smooth muscle actin and desmins in the spindle cells proliferated in the lymph nodes; no cytokeratin positivity was detected. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8752741",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 182,
"text": "We have raised monoclonal antibodies (Mab) to the Mr 55,000 desmin polypeptide, electrophoretically purified from cytoskeletal preparations of isolated bovine heart Purkinje fibers. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1694790",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 237,
"offsetInEndSection": 409,
"text": "Mesothelial and ovarian carcinoma cells could not be distinguished by (intermediate) filament typing, using monoclonal antibodies (MAbs) to keratins, vimentins and desmins.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2659540",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 201,
"text": "A fast and convenient procedure for the purification of polymerization-competent smooth-muscle desmin is described. Desmin from chicken gizzard and hog stomach were compared by fingerprint techniques. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7460905",
"endSection": "sections.0"
}
] |
513711055274a5fb0700000e | Are viruses involved in the etiology of human subacute thyroiditis? | Subacute thyroiditis (SAT) is an inflammatory disorder of the thyroid caused probably by viruses
The principal classes of viruses involed in SAT include Epstein Barr and Retroviridae | [
"18422033",
"19138419",
"20960165",
"11109652",
"23227861",
"22819125",
"19627727",
"20671410",
"22527824",
"1856259",
"1691523",
"18421188",
"12608662",
"22459018",
"20886354",
"9790279",
"10971829",
"4936649",
"10525005",
"22136271",
"15332726",
"16279854",
"9915102"
] | yesno | [
{
"offsetInBeginSection": 1,
"offsetInEndSection": 180,
"text": "he etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1856259",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 93,
"text": "Subacute thyroiditis is an inflammatory disorder of the thyroid caused probably by viruses. I",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11109652",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 713,
"offsetInEndSection": 853,
"text": "We believe that the etiologic agent was the Epstein-Barr virus because heterophile and Epstein-Barr virus-specific antibodies were positive.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11109652",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 711,
"offsetInEndSection": 1051,
"text": "ltogether, these results indicate that the mechanism of inhibition of Spumavirinae infection by interferon differs from that described for the other Retroviridae, and particularly for types B, C and D viruses. Our data is of therapeutic interest since Spumavirinae have been linked to pathological processes such as de Quervain thyroiditis.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1691523",
"endSection": "sections.0"
}
] |
56e30dd551531f7e33000016 | List core circadian clock genes. | The core circadian clock genes are CLOCK, BMAL1, Per, and Cry. | [
"24919398",
"24378737",
"25045881",
"25013953",
"24454829",
"25888034",
"26131842",
"25025868"
] | list | [
{
"offsetInBeginSection": 816,
"offsetInEndSection": 857,
"text": "PER1, CRY1, CRY2, CLOCK, BMAL1, and CKlε ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26131842",
"endSection": "abstract"
},
{
"offsetInBeginSection": 610,
"offsetInEndSection": 687,
"text": " Expression levels of five clock genes (Rev-Erbα, Per1, Per2, Bmal1 and Cry1)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25045881",
"endSection": "abstract"
},
{
"offsetInBeginSection": 510,
"offsetInEndSection": 584,
"text": "altered expression patterns of the circadian clock genes, Bmal1 and Per2. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888034",
"endSection": "abstract"
},
{
"offsetInBeginSection": 657,
"offsetInEndSection": 741,
"text": "This review will focus on the core circadian clock genes CLOCK, BMAL1, Per, and Cry.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25025868",
"endSection": "abstract"
},
{
"offsetInBeginSection": 990,
"offsetInEndSection": 1012,
"text": "CLOCK, RORA, and NPAS2",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24919398",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1185,
"offsetInEndSection": 1204,
"text": "Rev-erbα and Bmal1 ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25013953",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1352,
"offsetInEndSection": 1407,
"text": "he core circadian clock genes BMAL1, PER1/2 and CRY1/2.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24454829",
"endSection": "abstract"
},
{
"offsetInBeginSection": 312,
"offsetInEndSection": 360,
"text": "CLOCK/BMAL1, the core circadian clock components",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24378737",
"endSection": "abstract"
}
] |
5713c8d71174fb1755000015 | Which peripheral neuropathy has been associated with NDRG1 mutations? | Charcot-Marie-Tooth (CMT) 4D disease is a severe autosomal recessive demyelinating neuropathy with extensive axonal loss leading to early disability, caused by mutations in the N-myc downstream regulated gene 1 (NDRG1). | [
"20582309",
"15082788",
"12884740",
"15651351",
"12872253",
"16541790",
"23996628",
"21303696"
] | factoid | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 195,
"text": "CMT4D disease is a severe autosomal recessive demyelinating neuropathy with extensive axonal loss leading to early disability, caused by mutations in the N-myc downstream regulated gene 1 (NDRG1)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21303696",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 300,
"text": "In a previous study, we have shown that N-myc downstream-regulated gene 1 (NDRG1), classified in databases as a tumor suppressor and heavy metal-response protein, is mutated in hereditary motor and sensory neuropathy Lom (HMSNL), a severe autosomal recessive form of Charcot-Marie-Tooth (CMT) disease",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12872253",
"endSection": "abstract"
},
{
"offsetInBeginSection": 747,
"offsetInEndSection": 1289,
"text": "In the primary peripheral demyelinating neuropathies(CMT1), at least 9 genes have been associated with the disorders; altered dosage of peripheral myelin protein 22(PMP22) or point mutation of PMP22, the gap junction protein 1(GJB1), the myelin protein zero gene(MPZ), the early growth response gene 2(EGR2), the myotubularin-related protein 2 gene(MTMR2), the N-myc downstream-regulated gene 1 (NDRG1), the L-periaxin gene(PRX), SRY-related HMG-BOX gene 10(SOX10) and the ganglioside-induced differentiation-associated protein 1 gene(GDAP1).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12884740",
"endSection": "abstract"
},
{
"offsetInBeginSection": 939,
"offsetInEndSection": 1093,
"text": "The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20582309",
"endSection": "abstract"
},
{
"offsetInBeginSection": 977,
"offsetInEndSection": 1598,
"text": "Genetic studies have revealed the following gene mutations as the causes of inherited neuropathies; PMP22, MPZ, EGR2, SOX10, SIMPLE/LITAF, ARHGEF10 for CMT1 (autosomal dominant demyelinating form); GDAP1, MTMR2, SBF2/MTMR13, KIAA1985, NDRG1 PRX for CMT4 (autosomal recessive demyelinating form), MFN2, KIF1B, RAB7, GARS, NEFL, HSPB1, HSPB8 for CMT2 (autosomal dominant axonal form); LMNA, GAN1, KCC3, TDP1, APTX, SETX for AR-CMT2 (autosomal recessive axonal form); GIB1 for CMTX (X-linked CMT); DNM2 for CMT-DI (autosomal dominant CMT with intermediate nerve conduction velocities); and DHH for minifascicular neuropathy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16541790",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 301,
"text": "In a previous study, we have shown that N-myc downstream-regulated gene 1 (NDRG1), classified in databases as a tumor suppressor and heavy metal-response protein, is mutated in hereditary motor and sensory neuropathy Lom (HMSNL), a severe autosomal recessive form of Charcot-Marie-Tooth (CMT) disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12872253",
"endSection": "abstract"
},
{
"offsetInBeginSection": 439,
"offsetInEndSection": 702,
"text": "Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15082788",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 196,
"text": "CMT4D disease is a severe autosomal recessive demyelinating neuropathy with extensive axonal loss leading to early disability, caused by mutations in the N-myc downstream regulated gene 1 (NDRG1).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21303696",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1037,
"offsetInEndSection": 1252,
"text": "The success of molecular genetic analysis in all families confirms that autosomal recessive forms of CMT caused by mutations on the NDRG1 and HK1 genes are common causes of inherited neuropathies among Slovak Roma. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23996628",
"endSection": "abstract"
},
{
"offsetInBeginSection": 177,
"offsetInEndSection": 441,
"text": "Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15082788",
"endSection": "abstract"
},
{
"offsetInBeginSection": 208,
"offsetInEndSection": 616,
"text": "In the primary peripheral demyelinating neuropathies (CMT1), at least 15 genes have been associated with the disorders; altered dosage or point mutation of PMP22, GJB1, MPZ, EGR2, MTMR2, NDRG1, PRX, SOX10, GDAP1 and MTMR13/SBF2. In the primary peripheral axonal neuropathies (CMT2), at least 10 genes have been associated with these disorders; NEFL, KIF1B, MFN2, GAN1, LMNA, RAB7, GARS, TDP1, APTX, and SETX.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15651351",
"endSection": "abstract"
},
{
"offsetInBeginSection": 208,
"offsetInEndSection": 1018,
"text": "In the primary peripheral demyelinating neuropathies(CMT1), at least 9 genes have been associated with the disorders; altered dosage of peripheral myelin protein 22(PMP22) or point mutation of PMP22, the gap junction protein 1(GJB1), the myelin protein zero gene(MPZ), the early growth response gene 2(EGR2), the myotubularin-related protein 2 gene(MTMR2), the N-myc downstream-regulated gene 1 (NDRG1), the L-periaxin gene(PRX), SRY-related HMG-BOX gene 10(SOX10) and the ganglioside-induced differentiation-associated protein 1 gene(GDAP1). In the primary peripheral axonal neuropathies(CMT2), at least 8 genes have been associated with these disorders; the neurofilament light chain gene(NEFL), the kinesin 1B gene(KIF1B), the gigaxonin gene(GAN1), Lamin A/C(LMNA) and tyrosyl-DNA phosphodiesterase 1(TDP1).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12884740",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 441,
"text": " NDRG1 is an intracellular protein that is induced under a number of stress and pathological conditions, and it is thought to be associated with cell growth and differentiation. Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15082788",
"endSection": "abstract"
},
{
"offsetInBeginSection": 129,
"offsetInEndSection": 750,
"text": "Recent genetic studies have revealed their phenotypic and genetic diversities. In the primary peripheral demyelinating neuropathies(CMT1), at least 9 genes have been associated with the disorders; altered dosage of peripheral myelin protein 22(PMP22) or point mutation of PMP22, the gap junction protein 1(GJB1), the myelin protein zero gene(MPZ), the early growth response gene 2(EGR2), the myotubularin-related protein 2 gene(MTMR2), the N-myc downstream-regulated gene 1 (NDRG1), the L-periaxin gene(PRX), SRY-related HMG-BOX gene 10(SOX10) and the ganglioside-induced differentiation-associated protein 1 gene(GDAP1).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12884740",
"endSection": "abstract"
},
{
"offsetInBeginSection": 129,
"offsetInEndSection": 436,
"text": "Recent genetic studies have revealed their phenotypic and genetic diversities. In the primary peripheral demyelinating neuropathies (CMT1), at least 15 genes have been associated with the disorders; altered dosage or point mutation of PMP22, GJB1, MPZ, EGR2, MTMR2, NDRG1, PRX, SOX10, GDAP1 and MTMR13/SBF2.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15651351",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1428,
"offsetInEndSection": 1825,
"text": "Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20582309",
"endSection": "abstract"
},
{
"offsetInBeginSection": 208,
"offsetInEndSection": 436,
"text": "In the primary peripheral demyelinating neuropathies (CMT1), at least 15 genes have been associated with the disorders; altered dosage or point mutation of PMP22, GJB1, MPZ, EGR2, MTMR2, NDRG1, PRX, SOX10, GDAP1 and MTMR13/SBF2.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15651351",
"endSection": "abstract"
},
{
"offsetInBeginSection": 793,
"offsetInEndSection": 947,
"text": "The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20582309",
"endSection": "abstract"
},
{
"offsetInBeginSection": 208,
"offsetInEndSection": 750,
"text": "In the primary peripheral demyelinating neuropathies(CMT1), at least 9 genes have been associated with the disorders; altered dosage of peripheral myelin protein 22(PMP22) or point mutation of PMP22, the gap junction protein 1(GJB1), the myelin protein zero gene(MPZ), the early growth response gene 2(EGR2), the myotubularin-related protein 2 gene(MTMR2), the N-myc downstream-regulated gene 1 (NDRG1), the L-periaxin gene(PRX), SRY-related HMG-BOX gene 10(SOX10) and the ganglioside-induced differentiation-associated protein 1 gene(GDAP1).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12884740",
"endSection": "abstract"
},
{
"offsetInBeginSection": 178,
"offsetInEndSection": 441,
"text": "Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15082788",
"endSection": "abstract"
}
] |
51485008d24251bc05000028 | Is miR-126 involved in heart failure? | Yes, miR-126 is associated with heart failure. | [
"21157109",
"23465244"
] | yesno | [
{
"offsetInBeginSection": 1479,
"offsetInEndSection": 1714,
"text": "he miRNAs miR-126 and miR-508-5p are associated with the outcome of ICM and NICM patients with CHF. These two miRNAs could be useful in the diagnosis of CHF patients, and might provide novel targets for prevention and treatment of CHF.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23465244",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1099,
"offsetInEndSection": 1236,
"text": "The plasma concentration of miR-126 was negatively correlated with age and NYHA class, and could be a useful biomarker for heart failure.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21157109",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 949,
"offsetInEndSection": 1085,
"text": "In 10 patients with heart failure, plasma concentrations of miR-126 were up-regulated with improvement of the NYHA class from IV to III.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21157109",
"endSection": "sections.0"
}
] |
52e7bbf698d023950500001d | Does resveratrol reduce cardiac remodeling? | Resveratrol attenuates left ventricular remodeling.
Resveratrol is a beneficial pharmacological tool that augments autophagy to bring about reverse remodeling in the postinfarction heart.
Resveratrol administration improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function.
Resveratrol can constitute an adjuvant therapeutic option in prevention of dilated cardiomyopathy. | [
"22926332",
"22473781",
"20869962",
"23274061",
"18853243",
"19370079",
"18310510",
"22245452",
"18356487",
"20874677",
"20491649",
"22050707",
"12679191",
"18639559",
"20675566",
"19460403",
"19370081",
"20429690",
"21352470",
"17488730",
"20008278",
"19942861",
"19959541",
"18562309",
"20716127",
"17875610",
"16198371",
"22768138",
"15498824",
"23784505",
"24289075",
"22229508",
"21054406"
] | yesno | [
{
"offsetInBeginSection": 1199,
"offsetInEndSection": 1498,
"text": "In conclusion, resveratrol attenuated cardiac oxidative damage and left ventricular remodeling and enhanced the decreased expression of SIRT1 in hearts of old rats with emphysema and thus might be a therapeutic modality for cardiac injury complicated in chronic obstructive pulmonary disease (COPD).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24289075",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1547,
"offsetInEndSection": 1697,
"text": "In conclusion, resveratrol is a beneficial pharmacological tool that augments autophagy to bring about reverse remodeling in the postinfarction heart.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23274061",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1794,
"offsetInEndSection": 2214,
"text": "Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22768138",
"endSection": "abstract"
}
] |
51bdd9c2047fa84d1d000002 | Which is the receptor for substrates of Chaperone Mediated Autophagy? | Chaperone-mediated autophagy (CMA) is a lysosomal pathway for selective removal of damaged cytosolic proteins. The LAMP2A (Lysosome-associated membrane protein 2 isoform A) functions as a receptor for cytosolic proteins and also as essential component of the CMA translocation complex [28]. Cytosolic substrate proteins bind to monomers of LAMP-2A, which then multimerizes to form the complex required for substrate transmembrane import. | [
"18635949",
"22331875",
"15331765",
"18550537",
"11208145",
"11082038",
"22809326",
"19117012",
"18644871",
"21429245",
"23070014",
"23404999",
"21966475",
"21514572",
"18927485",
"19433452",
"12505983",
"15325583",
"22426402",
"17284523",
"16585521",
"10806201",
"22227450",
"22363588",
"22653298"
] | factoid | [
{
"offsetInBeginSection": 149,
"offsetInEndSection": 346,
"text": "These proteins are targeted by chaperones and delivered to lysosomes where they are translocated into the lysosomal lumen and degraded via the lysosome-associated membrane protein type 2A (LAMP-2A)",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23404999",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1165,
"offsetInEndSection": 1432,
"text": "Macroautophagy is followed by chaperone-mediated autophagy (CMA), in which Hsc70 (Heat shock cognate 70) selectively binds proteins with exposed KFERQ motifs and pushes them inside lysosomes through the LAMP-2A (Lysosome-associated membrane protein type 2A) receptor.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23070014",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 671,
"offsetInEndSection": 756,
"text": "CMA activity has been shown to be proportional to levels of the CMA receptor Lamp-2a.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22426402",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 747,
"offsetInEndSection": 900,
"text": "Lysosomes from livers of lipid-challenged mice had a marked decrease in the levels of the CMA receptor, the lysosome-associated membrane protein type 2A,",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22331875",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 994,
"offsetInEndSection": 1171,
"text": "We report that Bcl-2-related early rod apoptosis was associated with the upregulation of autophagy markers including chaperone-mediated autophagy (CMA) substrate receptor LAMP-2",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22227450",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 617,
"offsetInEndSection": 710,
"text": "we examined gene expression levels of lysosome-associated membrane 2 (LAMP-2), a CMA receptor",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21514572",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 110,
"offsetInEndSection": 236,
"text": "The lysosomal-membrane protein type 2A (LAMP-2A) acts as the receptor for the substrates of chaperone-mediated autophagy (CMA)",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18927485",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 373,
"text": "Chaperone-mediated autophagy (CMA) is a selective type of autophagy by which specific cytosolic proteins are sent to lysosomes for degradation. Substrate proteins bind to the lysosomal membrane through the lysosome-associated membrane protein type 2A (LAMP-2A), one of the three splice variants of the lamp2 gene, and this binding is limiting for their degradation via CMA.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18644871",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 662,
"offsetInEndSection": 837,
"text": "Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18644871",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 266,
"offsetInEndSection": 394,
"text": "We recently reported that UCH-L1 physically interacts with LAMP-2A, the lysosomal receptor for chaperone-mediated autophagy (CMA",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18635949",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 460,
"offsetInEndSection": 562,
"text": "In this study, we found that UCH-L1 physically interacts with LAMP-2A, the lysosomal receptor for CMA,",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18550537",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 113,
"offsetInEndSection": 406,
"text": "We have previously described an age-related decline in chaperone-mediated autophagy (CMA), a selective form of autophagy, by which particular cytosolic proteins are delivered to lysosomes after binding to the lysosome-associated membrane protein type 2A (LAMP-2A), a receptor for this pathway.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17284523",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 266,
"text": "Chaperone-mediated autophagy (CMA) is a selective pathway for the degradation of cytosolic proteins in lysosomes. CMA declines with age because of a decrease in the levels of lysosome-associated membrane protein (LAMP) type 2A, a lysosomal receptor for this pathway.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16585521",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 543,
"offsetInEndSection": 853,
"text": "Oxidation-induced activation of CMA correlates with higher levels of several components of the lysosomal translocation complex, but in particular of the lumenal chaperone, required for substrate uptake, and of the lysosomal membrane protein (lamp) type 2a, previously identified as a receptor for this pathway.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15331765",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 112,
"offsetInEndSection": 296,
"text": "We now demonstrate that this protease activity triggers the degradation of the lysosome-associated membrane protein type 2a (lamp2a), a receptor for chaperone-mediated autophagy (CMA).",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12505983",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 185,
"offsetInEndSection": 289,
"text": "We have previously identified this receptor as the lysosome-associated membrane protein type 2a (lamp2a)",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11208145",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 107,
"text": "Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11082038",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1007,
"offsetInEndSection": 1111,
"text": "These characteristics may be important for lamp2a to act as a receptor for chaperone-mediated autophagy.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11082038",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 603,
"offsetInEndSection": 760,
"text": "A progressive age-related decrease in the levels of the lysosome-associated membrane protein type 2a that acts as a receptor for chaperone-mediated autophagy",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10806201",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 584,
"offsetInEndSection": 736,
"text": "Hsc70 and Hsp40 are members of a molecular chaperone complex required for protein transport into the lysosome during chaperone-mediated autophagy (CMA).",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19117012",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 430,
"offsetInEndSection": 696,
"text": "Once there, substrate proteins bind to the lysosome-associated membrane protein type 2 isoform A (LAMP2A), inducing assembly of this receptor protein into a higher molecular weight protein complex that is used by the substrate proteins to reach the lysosomal lumen. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22653298",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 428,
"offsetInEndSection": 549,
"text": "Protein substrates bind to a receptor in the lysosomal membrane, the lysosome-associated membrane protein (lamp) type 2a.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15325583",
"endSection": "sections.0"
}
] |
54d892ee014675820d000005 | What are the hallmarks of congestive heart failure? | Congestive heart failure (HF) is a clinical syndrome, with hallmarks of fatigue and dyspnea, that continues to be highly prevalent and morbid. Common pathophysiologic features of HF include changes in left ventricle structure, function, and neurohormonal activation. Disturbed myocardial calcium handling is also one of the pathophysiologic hallmarks of congestive heart failure. One of the hallmarks of chronic congestive heart failure is an increase in sympathetic tone to the peripheral circulation and to the heart. It has been proposed that the activation of neurohormonal pathways and the formation of oxygen free radicals ultimately lead to the activation of a family of transcription factors that are involved in cardiac and vascular remodelling which are hallmarks of congestive heart failure. Myocardial failure ultimately leads to exaggerated neurohumoral compensatory mechanisms and derangements of the peripheral circulation, which are the hallmarks of congestive heart failure. Two additional hallmarks of this syndrome are sodium and water retention. Accumulation of oxidized matrix between the endothelium and cardiac muscle, and endocardial endothelial dysfunction, are also hallmarks of congestive heart failure. | [
"12691636",
"7777669",
"22707076",
"17922627",
"19808348",
"1357906",
"2936238",
"9519348",
"11930867"
] | summary | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 146,
"text": "Disturbed myocardial calcium (Ca(+)) handling is one of the pathophysiologic hallmarks of cardiovascular diseases such as congestive heart failure",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22707076",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 142,
"text": "Congestive heart failure (HF) is a clinical syndrome, with hallmarks of fatigue and dyspnea, that continues to be highly prevalent and morbid.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19808348",
"endSection": "abstract"
},
{
"offsetInBeginSection": 312,
"offsetInEndSection": 435,
"text": "Common pathophysiologic features of HF include changes in left ventricle structure, function, and neurohormonal activation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19808348",
"endSection": "abstract"
},
{
"offsetInBeginSection": 736,
"offsetInEndSection": 831,
"text": "the compensatory neurohormonal systems and ventricular remodeling that are the hallmarks of CHF",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11930867",
"endSection": "abstract"
},
{
"offsetInBeginSection": 168,
"offsetInEndSection": 361,
"text": "The most important processes to be activated in heart failure are the neurohormonal systems, which include the reninangiotensin system, the sympathetic nervous system and the endothelin system.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9519348",
"endSection": "abstract"
},
{
"offsetInBeginSection": 404,
"offsetInEndSection": 492,
"text": "the formation of reactive oxygen free radicals is increased in congestive heart failure.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9519348",
"endSection": "abstract"
},
{
"offsetInBeginSection": 493,
"offsetInEndSection": 775,
"text": "It has been proposed that the activation of neurohormonal pathways and the formation of oxygen free radicals ultimately lead to the activation of a family of transcription factors that are involved in cardiac and vascular remodelling which are hallmarks of congestive heart failure.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9519348",
"endSection": "abstract"
},
{
"offsetInBeginSection": 372,
"offsetInEndSection": 560,
"text": "Myocardial failure ultimately leads to exaggerated neurohumoral compensatory mechanisms and derangements of the peripheral circulation, which are the hallmarks of congestive heart failure.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2936238",
"endSection": "abstract"
},
{
"offsetInBeginSection": 80,
"offsetInEndSection": 183,
"text": "The two hallmarks of this syndrome, sodium and water retention, are frequently a therapeutic challenge.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17922627",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 163,
"text": "Accumulation of oxidized matrix between the endothelium and cardiac muscle, and endocardial endothelial dysfunction, are the hallmarks of congestive heart failure.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12691636",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 250,
"text": "One of the hallmarks of chronic congestive heart failure is an increase in sympathetic tone to the peripheral circulation and to the heart. A correlation between plasma norepinephrine and the severity of the heart failure state has been demonstrated.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7777669",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 207,
"text": "Disturbed myocardial calcium (Ca(+)) handling is one of the pathophysiologic hallmarks of cardiovascular diseases such as congestive heart failure, cardiac hypertrophy, and certain types of tachyarrhythmias.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22707076",
"endSection": "abstract"
},
{
"offsetInBeginSection": 372,
"offsetInEndSection": 559,
"text": "Myocardial failure ultimately leads to exaggerated neurohumoral compensatory mechanisms and derangements of the peripheral circulation, which are the hallmarks of congestive heart failure",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2936238",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 138,
"text": "One of the hallmarks of chronic congestive heart failure is an increase in sympathetic tone to the peripheral circulation and to the heart",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7777669",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 97,
"text": "Myocardial pump deficiency is regarded to be the hemodynamic hallmark of congestive heart failure",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1357906",
"endSection": "abstract"
}
] |
52f509512059c6d71c000020 | What is the mode of inheritance of short QT syndrome? | The short QT syndrome has an autosomal dominant mode of inheritance. | [
"19829181",
"16812977",
"19482666"
] | factoid | [
{
"offsetInBeginSection": 259,
"offsetInEndSection": 552,
"text": "Congenital short QT syndrome is a new familial primary electrical disease of the heart, which is characterized by abnormally short QT interval and paroxysmal atrial and ventricular tachyarrhythmias, including sudden cardiac death. An autosomal dominant mode of inheritance has been suggested. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19482666",
"endSection": "abstract"
},
{
"offsetInBeginSection": 362,
"offsetInEndSection": 924,
"text": "From 1993, the Short QT Syndrome (SQTS) came to our attention, as a new inherited \"electrical disease\" associated with increased risk of sudden cardiac death and atrial fibrillation. Mutations of Ikr, Iks, Ikl channels cause dysfunctional Iks, Ikr, Ikl channels with an increase in the net outward K current leading to shortening of repolarization. This in turn leads to a shorter QT interval on the ECG and shorter atrial and ventricular refractory periods with increased susceptibility to VF and AF. There seems to be an autosomal dominant mode of inheritance.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16812977",
"endSection": "abstract"
}
] |
530e0d6e5937551c09000001 | List clinical trials that have directly compared microsurgical clipping with endovascular coiling for treatment of ruptured brain aneurysms? | Barrow Ruptured Aneurysm Trial (BRAT) and international subarachnoid aneurysmal trial (ISAT) have directly compared microsurgical clipping with endovascular coiling for treatment of ruptured brain aneurysms. FIAT study, a clinical care trial aiming to compare angiographic and clinical outcomes following treatment with a Flow-Diverter or with the best conventional treatment option (including clipping) is underway. | [
"20808697",
"23210044",
"17703631",
"18053204",
"16172968",
"21947244",
"19329361",
"23621600",
"23607065",
"21898188",
"16139655",
"23049642",
"23964263",
"12414200",
"20165722",
"21696651"
] | list | [
{
"offsetInBeginSection": 8,
"offsetInEndSection": 377,
"text": "The authors report the 3-year results of the Barrow Ruptured Aneurysm Trial (BRAT). The objective of this ongoing randomized trial is to compare the safety and efficacy of microsurgical clip occlusion and endovascular coil embolization for the treatment of acutely ruptured cerebral aneurysms and to compare functional outcomes based on clinical and angiographic data. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23621600",
"endSection": "abstract"
},
{
"offsetInBeginSection": 512,
"offsetInEndSection": 973,
"text": "We report the design of the FIAT study, a clinical care trial aiming to compare angiographic and clinical outcomes following treatment with a Flow-Diverter or with the best conventional treatment option. The FIAT study will include both a randomized and a registry portion. Patients will be proposed randomization to either FD stenting or best conventional treatment option (observation, coiling, stenting, or clipping) as determined by the treating physician. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21696651",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 140,
"text": "The effect of clipping and coiling in acute severe subarachnoid hemorrhage after international subarachnoid aneurysmal trial (ISAT) results.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16172968",
"endSection": "title"
},
{
"offsetInBeginSection": 1422,
"offsetInEndSection": 1534,
"text": "A critical appraisal of the ISAT of microsurgical clipping versus coiling is used for comparison of our results.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16172968",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 274,
"text": "International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16139655",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 177,
"text": "International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12414200",
"endSection": "title"
}
] |
530cf54dab4de4de0c000009 | What is the reason for the narcolepsy cases developed after H1N1 influenza vaccination? | The proposed mechanism for postvaccination narcolepsy is one in which an environmental trigger causes or enhances an antibody-mediated autoimmune response in patients with a preexisting genetic susceptibility. | [
"21866560",
"23486871",
"24048081",
"23884811",
"21963829",
"21676420",
"22530521",
"22213222"
] | summary | [
{
"offsetInBeginSection": 747,
"offsetInEndSection": 957,
"text": "The proposed mechanism for postvaccination narcolepsy is one in which an environmental trigger causes or enhances an antibody-mediated autoimmune response in patients with a preexisting genetic susceptibility. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24048081",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 224,
"text": "The loss of hypothalamic hypocretin/orexin (hcrt) producing neurons causes narcolepsy with cataplexy. An autoimmune basis for the disease has long been suspected and recent results have greatly strengthened this hypothesis. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21963829",
"endSection": "abstract"
},
{
"offsetInBeginSection": 663,
"offsetInEndSection": 776,
"text": "pointing towards processes such as molecular mimicry or bystander activation as crucial for disease development. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21963829",
"endSection": "abstract"
},
{
"offsetInBeginSection": 581,
"offsetInEndSection": 840,
"text": "Although no formal link can be established, the unusual characteristics of the reported cases and the striking temporal relationship suggests that narcolepsy may be the result of an autoimmune reaction triggered by H1N1 vaccination in susceptible individuals.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21676420",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1141,
"offsetInEndSection": 1251,
"text": "Pandemrix vaccination is a precipitating factor for narcolepsy, especially in combination with HLA-DQB1*0602. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23486871",
"endSection": "abstract"
},
{
"offsetInBeginSection": 363,
"offsetInEndSection": 524,
"text": "Recently identified autoantibodies to Tribbles homologue 2 in some patients, as well as cases associated with H1N1 vaccination, support an autoimmune mechanism. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22213222",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1367,
"offsetInEndSection": 1701,
"text": "n China, narcolepsy onset is highly correlated with seasonal and annual patterns of upper airway infections, including H1N1 influenza. In 2010, the peak seasonal onset of narcolepsy was phase delayed by 6 months relative to winter H1N1 infections, and the correlation was independent of H1N1 vaccination in the majority of the sample.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21866560",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2016,
"offsetInEndSection": 2141,
"text": "H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23884811",
"endSection": "abstract"
}
] |
5311bf53e3eabad021000006 | Which are the biotracers used for detection of Alzheimer's disease using PET? | Pittsburgh compound B (PIB) was the first radiotracer capable of highlighting deposits of beta-amyloid—one pathological hallmark of Alzheimer's disease—in living individuals during a PET scan. The Alzheimer's Association helped fund early PIB development. The Association in 2006 also awarded a $2.1 million grant to the Alzheimer's Disease Neuroimaging Initiative (ADNI) to expand this long-term, nationwide study to include PIB-PET imaging.
18F flutemetamol (flute), another radiotracer that highlights beta-amyloid in a PET scan, is structurally identical to PIB except for one fluorine atom in place of a carbon atom. That small chemical change enables flutemetamol to remain stable significantly longer than does PIB, potentially increasing its usefulness outside research settings. In phase II study results reported in the Annals of Neurology, flutemetamol performed similarly to PIB. Additional testing is under way.
Florbetapir F 18 (18F-AV-45) is also a radiotracer that highlights brain beta-amyloid during a PET scan. At the 2010 Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD), florbetapir's developer first reported data, later published in the JAMA, showing nearly perfect correlation between brain amyloid levels detected by florbetapir PET scans in study volunteers and levels found in autopsies of the same individuals a few months later. The developer has sought Food and Drug Administration (FDA) approval to market florbetapir under the brand name Amyvid. The FDA has said it will withhold approval until the developer establishes a professional training program to ensure accuracy and consistency in reading and interpreting Amyvid scans.
Florbetaben (BAY 94-9172) is another radiotracer designed to detect beta-amyloid during a PET scan. Phase II study results and other florbetaben data were reported at the 2010 Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD). Phase II data were also later published in Lancet Neurology. Further studies are now under way. | [
"22982358",
"23966249",
"23624169",
"23882370",
"24194552",
"24166579",
"23527322",
"20580647",
"21683932",
"24199960",
"17182990",
"21624562",
"23966257",
"23420460",
"18620875",
"18191617",
"15783264",
"23597030",
"23178035",
"19164222",
"16712496",
"21764791",
"24132372",
"23536396",
"23053137",
"23995816",
"19142702"
] | list | [
{
"offsetInBeginSection": 1292,
"offsetInEndSection": 1512,
"text": "(18)F-flutemetamol PET and structural MRI provided additive information in the diagnostic classification of aMCI subjects, suggesting an amyloid-independent neurodegenerative component among aMCI subjects in this sample.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23178035",
"endSection": "abstract"
},
{
"offsetInBeginSection": 138,
"offsetInEndSection": 435,
"text": "This pooled analysis of four studies determined the level of association between uptake of the fibrillar amyloid β positron emission tomography (PET) imaging agent [(18)F]flutemetamol (Pittsburgh Compound B analog with a 5.5 times longer half-life to enable it to be used in the clinical setting) ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23053137",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 557,
"text": "is implicated in the development of late-onset Alzheimer's disease (AD). We sought to determine the associations between beta amyloid (Aβ) plaque deposition in vivo using Pittsburgh compound B (PiB) and several indices of cholesterol homeostasis (i.e., total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein E (ApoE), clusterin, oxysterol metabolites of cholesterol, and previously reported genes associated with late-onset AD) in 175 nondemented elderly subjects. High Aβ dep",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24199960",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 406,
"text": "g biomarkers of Alzheimer's disease include amyloid deposition [imaged with [(11)C]Pittsburgh compound B (PiB) PET], altered glucose metabolism (imaged with [(18)F]fluro-deoxyglucose PET), and structural atrophy (imaged by MRI). Recently we published the initial subset of imaging findings for specific regions in a cohort of individuals with autosomal dominant Alzheimer's disease. We now exte",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24194552",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 428,
"text": "Criteria for preclinical Alzheimer disease (AD) propose β-amyloid (Aβ) plaques to initiate neurodegeneration within AD-affected regions. However, some cognitively normal older individuals harbor neural injury similar to patients with AD, without concurrent Aβ burden. Such findings challenge the proposed sequence and suggest that Aβ-independent precursors underlie AD-typical neurodegenerative patterns. OBJECTIVE T",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24166579",
"endSection": "abstract"
},
{
"offsetInBeginSection": 16,
"offsetInEndSection": 1814,
"text": "ol is a positron emission tomography (PET) tracer for in vivo amyloid imaging. The ability to classify amyloid scans in a binary manner as 'normal' versus 'Alzheimer-like', is of high clinical relevance. We evaluated whether a supervised machine learning technique, support vector machines (SVM), can replicate the assignments made by visual readers blind to the clinical diagnosis, which image components have highest diagnostic value according to SVM and how (18)F-flutemetamol-based classification using SVM relates to structural MRI-based classification using SVM within the same subjects. By means of SVM with a linear kernel, we analyzed (18)F-flutemetamol scans and volumetric MRI scans from 72 cases from the (18)F-flutemetamol phase 2 study (27 clinically probable Alzheimer's disease (AD), 20 amnestic mild cognitive impairment (MCI), 25 controls). In a leave-one-out approach, we trained the (18)F-flutemetamol based classifier by means of the visual reads and tested whether the classifier was able to reproduce the assignment based on visual reads and which voxels had the highest feature weights. The (18)F-flutemetamol based classifier was able to replicate the assignments obtained by visual reads with 100% accuracy. The voxels with highest feature weights were in the striatum, precuneus, cingulate and middle frontal gyrus. Second, to determine concordance between the gray matter volume- and the (18)F-flutemetamol-based classification, we trained the classifier with the clinical diagnosis as gold standard. Overall sensitivity of the (18)F-flutemetamol- and the gray matter volume-based classifiers were identical (85.2%), albeit with discordant classification in three cases. Specificity of the (18)F-flutemetamol based classifier was 92% compared to 68% for MRI. In the MCI ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22982358",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 1598,
"text": "disease (AD) is defined histologically by the presence of extracellular β-amyloid (Aβ) plaques and intraneuronal neurofibrillary tangles in the cerebral cortex. The diagnosis of dementia, along with the prediction of who will develop dementia, has been assisted by magnetic resonance imaging and positron emission tomography (PET) by using [(18)F]fluorodeoxyglucose (FDG). These techniques, however, are not specific for AD. Based on the chemistry of histologic staining dyes, several Aβ-specific positron-emitting radiotracers have been developed to image neuropathology of AD. Among these, [(11)C]PiB is the most studied Aβ-binding PET radiopharmaceutical in the world. The histologic and biochemical specificity of PiB binding across different regions of the AD brain was demonstrated by showing a direct correlation between Aβ-containing amyloid plaques and in vivo [(11)C]PiB retention measured by PET imaging. Because (11)C is not ideal for commercialization, several (18)F-labeled tracers have been developed. At this time, [(18)F]3'-F-PiB (Flutemetamol), (18)F-AV-45 (Florbetapir), and (18)F-AV-1 (Florbetaben) are undergoing extensive phase II and III clinical trials. This article provides a brief review of the amyloid biology and chemistry of Aβ-specific (11)C and (18)F-PET radiopharmaceuticals. Clinical trials have clearly documented that PET radiopharmaceuticals capable of assessing Aβ content in vivo in the brains of AD subjects and subjects with mild cognitive impairment will be important as diagnostic agents to detect in vivo amyloid brain pathology. In addition,",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21624562",
"endSection": "abstract"
},
{
"offsetInBeginSection": 24,
"offsetInEndSection": 1758,
"text": "is well known that many clinical and genetic factors have been associated with beta-amyloid deposition, few studies have examined the interactions of such factors across different stages of Alzheimer's pathogenesis. METHODS: We used 18F-florbetapir F18 PET imaging to quantify neuritic beta-amyloid plaque density across four cortical regions in 602 elderly (55-94 years) subjects from the national ADNI biomarker study. The group comprised of 194 normal elderly, 212 early mild cognitive impairment [EMCI], 132 late mild cognitive impairment [LMCI], and 64 mild Alzheimer's (AD). FINDINGS: In a model incorporating multiple predictive factors, the effect of apolipoprotein E ε4 and diagnosis was significant on all four cortical regions. The highest signals were seen in cingulate followed by frontal and parietal with lowest signals in temporal lobe (p<0.0001). The effect of apolipoprotein E ε4 (Cohen's D 0.96) on beta-amyloid plaque density was approximately twice as large as the effect of a diagnosis of AD (Cohen's D 0.51) and thrice as large as the effect of a diagnosis of LMCI (Cohen's D 0.34) (p<0.0001). Surprisingly, ApoE ε4+ normal controls had greater mean plaque density across all cortical regions than ε4- EMCI and ε4- LMCI (p<0.0001, p=0.0009) and showed higher, though non-significant, mean value than ε4- AD patients (p<0.27). ApoE ε4+ EMCI and LMCI subjects had significantly greater mean plaque density across all cortical regions than ε4- AD patients (p<0.027, p<0.0001). INTERPRETATION: Neuritic amyloid plaque load across progressive clinical stages of AD varies strongly by ApoE4 genotype. These findings support the need for better pathology-based and supported diagnosis in routine practice. Our data als",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23624169",
"endSection": "abstract"
},
{
"offsetInBeginSection": 140,
"offsetInEndSection": 1155,
"text": "sitron emission tomography (PET) radiotracers, fluorodeoxyglucose F 18 ((18)F-FDG) is the compound most widely used in the diagnosis of neurodegenerative dementias. However, this compound shows a level of specificity and sensitivity for early Alzheimer's disease detection that is lower than that provided by high-affinity ligands for β-amyloid (Aβ). Among the new widely available fluorine 18 ((18)F)-labeled Aβ ligands, florbetapir F 18 ((18))F-AV-45; Amyvid™) showed clear qualitative and quantitative correlations between in vivo PET imaging and postmortem histopathologic analysis of Aβ. Florbetapir F 18 stands out for its high Aβ affinity and its pharmacokinetic properties that allow 10-minute PET scan imaging within 90 minutes after administration (dose = 370 MBq). Importantly, no safety concerns for florbetapir F 18 were found in preclinical studies. In 2012, the U.S. Food and Drug Administration (FDA) approved Amyvid as a radiotracer helpful for excluding the presence of Aβ in the brain. It was the",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23527322",
"endSection": "abstract"
},
{
"offsetInBeginSection": 24,
"offsetInEndSection": 472,
"text": " (Abeta) plaque formation is a hallmark of Alzheimer's disease (AD) and precedes the onset of dementia. Abeta imaging should allow earlier diagnosis, but clinical application is hindered by the short decay half-life of current Abeta-specific ligands. (18)F-BAY94-9172 is an Abeta ligand that, due to the half-life of (18)F, is suitable for clinical use. We thus studied the effectiveness of this ligand in identifying patients with AD. METHODS: 15 ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18191617",
"endSection": "abstract"
}
] |
569e79ecceceede94d000002 | What was the purpose of the FANTOM3 project? | The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species | [
"16683036",
"20428234",
"16381948"
] | factoid | [
{
"offsetInBeginSection": 1558,
"offsetInEndSection": 1818,
"text": " The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16683036",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1094,
"offsetInEndSection": 1249,
"text": "Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1245,
"offsetInEndSection": 1435,
"text": "These databases were provided for Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948",
"endSection": "abstract"
},
{
"offsetInBeginSection": 321,
"offsetInEndSection": 520,
"text": "Sequencing projects, such as Fantom3 for mouse and H-InvDB for human, have generated abundant data on transcribed components of mammalian cells, the majority of which appear not to be protein-coding.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20428234",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1062,
"offsetInEndSection": 1253,
"text": "These databases were provided for Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948",
"endSection": "abstract"
},
{
"offsetInBeginSection": 135,
"offsetInEndSection": 335,
"text": "Sequencing projects, such as Fantom3 for mouse and H-InvDB for human, have generated abundant data on transcribed components of mammalian cells, the majority of which appear not to be protein-coding. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20428234",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1074,
"offsetInEndSection": 1357,
"text": "These databases were provided for Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses. Now access is free for all users through the World Wide Web at http://fantom3.gsc.riken.jp/.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948",
"endSection": "abstract"
},
{
"offsetInBeginSection": 124,
"offsetInEndSection": 323,
"text": "Sequencing projects, such as Fantom3 for mouse and H-InvDB for human, have generated abundant data on transcribed components of mammalian cells, the majority of which appear not to be protein-coding.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20428234",
"endSection": "abstract"
},
{
"offsetInBeginSection": 992,
"offsetInEndSection": 1264,
"text": "Their associations and TU attributes are available to find promoters of interest. These databases were provided for Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1074,
"offsetInEndSection": 1343,
"text": "These databases were provided for Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses. Now access is free for all users through the World Wide Web at http://fantom3.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948",
"endSection": "abstract"
}
] |
515bd543298dcd4e51000001 | In which isochores are Alu elements enriched? | Alu elements are enriched in high GC% isochores due to reduced Alu loss by recombination in these regions. The frequency of Alu sequences increases with increasing GC, but attains a maximum in H2 isochores. | [
"8828040",
"19543403",
"9931467",
"15871047",
"22057813",
"11591470",
"6572942",
"7723057"
] | list | [
{
"offsetInBeginSection": 146,
"offsetInEndSection": 241,
"text": " the vast majority of Alu sequences were shown to have the highest density in GC-rich isochores",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22057813",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 988,
"offsetInEndSection": 1103,
"text": "Alu sequences being unstable in the GC-poor isochores but stable in the compositionally matching GC-rich isochores,",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22057813",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 152,
"text": "Alu retrotransposons do not show a homogeneous distribution over the human genome but have a higher density in GC-rich (H) than in AT-rich (L) isochores",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15871047",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1230,
"offsetInEndSection": 1463,
"text": "This result, together with the known higher selective disadvantage of recombination products in H isochores, points to Alu-Alu recombination as the main agent provoking the density shift of Alus toward the GC-rich parts of the genome",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15871047",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 175,
"offsetInEndSection": 235,
"text": "whereas GC-rich Alus are mostly present in GC-rich isochores",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11591470",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1221,
"offsetInEndSection": 1469,
"text": "the present results on Alu and LINE stability/exclusion predict significant losses of Alu DNA from the GC-poor isochores during evolution, a phenomenon apparently due to negative selection against sequences that differ from the isochore composition",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11591470",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 780,
"offsetInEndSection": 929,
"text": "The frequency of Alu sequences also increases with increasing GC, but attains a maximum in H2 isochores, in agreement with previous experimental data",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9931467",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1570,
"offsetInEndSection": 1643,
"text": "The CpG levels of both Alus and CpG islands increase with their GC levels",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9931467",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 327,
"offsetInEndSection": 416,
"text": "characterized as a GC-rich isochore enriched for CpG islands, genes, and Alu-like repeats",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8828040",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1299,
"offsetInEndSection": 1414,
"text": "Microsatellites and SINES (Alu, B1, B2) are found at roughly equal frequencies in introns from all isochore classes",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7723057",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 500,
"offsetInEndSection": 776,
"text": "The results indicate that the short repeats of the B1 family of mouse and of the Alu I family of man are most frequent in the heavy components, whereas the long repeats of the BamHI family of mouse and of the Kpn I family of man are mainly present in the two light components.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/6572942",
"endSection": "sections.0"
}
] |
52df887498d023950500000c | Is oxalate renal excretion increased after bariatric surgery? | Bariatric surgery is associated with a significant risk of nephrolithiasis.
Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of bariatric surgery
Hyperoxaluria in patients treated with bariatric surgery was found to be a result of hyperabsorption of oxalate | [
"21295813",
"23821183",
"16925274",
"18701613",
"2218396",
"9689695",
"23024163",
"20566568",
"19762051",
"19013593",
"18501812",
"16217311",
"17222634",
"22554593",
"2669121"
] | yesno | [
{
"offsetInBeginSection": 280,
"offsetInEndSection": 630,
"text": "Despite the fact that bariatric surgery-induced weight loss is associated with a significant decrease in morbidity and mortality and improvement in renal function, bariatric surgery has recently been shown to be associated with a significant risk of nephrolithiasis. The main risk factor for nephrolithiasis is increased excretion of urinary oxalate.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20566568",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1444,
"offsetInEndSection": 1557,
"text": "Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of RYGBP.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16925274",
"endSection": "abstract"
},
{
"offsetInBeginSection": 552,
"offsetInEndSection": 724,
"text": "The urinary excretion of oxalate was high: 1.112 mumol/24 h (normal range: 55-400 mumol/24 h), and citrate excretion was low: 1.48 mmol/24 h (normal range: 2-5 mmol/24 h). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9689695",
"endSection": "abstract"
},
{
"offsetInBeginSection": 744,
"offsetInEndSection": 981,
"text": "Hyperoxaluria in patients with JIB was found to be a result of hyperabsorption of oxalate, and these patients displayed altered oxalate kinetics with continued urinary excretion of orally administered 14C-oxalate for more than 48 hours. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2669121",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1086,
"offsetInEndSection": 1517,
"text": "Malabsorption of calcium and low fasting urinary calcium excretion in the JIB patients were associated with high tubular reabsorption of calcium, the latter presumably attributable to a compensatory increase in circulating parathyroid hormone (PTH). In most recurrent renal stone formers the urinary calcium concentration was increased, with an inverse relationship to serum PTH, indicating intestinal hyperabsorption of calcium. A",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2669121",
"endSection": "abstract"
}
] |
52e6c92598d0239505000019 | Which are the mutational hotspots of the human KRAS oncogene? | The KRAS oncogene has four main mutational hotspots located at codons 12, 13, 61 and 146. | [
"23074403",
"19430299",
"16458330",
"22006429",
"23536897",
"21199003",
"11403720",
"16434186",
"21266528",
"12650907",
"10768832",
"14534542",
"12941809",
"17638058"
] | list | [
{
"offsetInBeginSection": 613,
"offsetInEndSection": 726,
"text": "In this study we analyzed 15 sMTC for mutations in the hotspots codon 12, 13 and 61 of the H- and K-ras oncogene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10768832",
"endSection": "abstract"
},
{
"offsetInBeginSection": 824,
"offsetInEndSection": 891,
"text": "mutation in the codon 12, 13 and 61 of the H-ras and K-ras oncogene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10768832",
"endSection": "abstract"
},
{
"offsetInBeginSection": 31,
"offsetInEndSection": 155,
"text": "the mutation hotspots of the K-ras proto-oncogene in human functional adrenocortical tumors are in codons 15, 16, 18, and 31",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11403720",
"endSection": "abstract"
},
{
"offsetInBeginSection": 4,
"offsetInEndSection": 130,
"text": "mutations C742T, G746T, G747T in the TP53 gene and G35T in the KRAS gene have been repeatedly found in sectors of human tumors",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16458330",
"endSection": "abstract"
},
{
"offsetInBeginSection": 272,
"offsetInEndSection": 293,
"text": "exons 1 and 2 of KRAS",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21266528",
"endSection": "abstract"
},
{
"offsetInBeginSection": 303,
"offsetInEndSection": 329,
"text": "KRAS (codon 12/13 hotspot)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21199003",
"endSection": "abstract"
},
{
"offsetInBeginSection": 662,
"offsetInEndSection": 711,
"text": "three hotspots in KRAS (codons 12/13, 61 and 146)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21199003",
"endSection": "abstract"
},
{
"offsetInBeginSection": 762,
"offsetInEndSection": 791,
"text": "analysis of KRAS (codon12/13)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21199003",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2359,
"offsetInEndSection": 2440,
"text": "mutations occurring in mutational hotspots (codons 12 and 13) of the KRAS protein",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23074403",
"endSection": "abstract"
},
{
"offsetInBeginSection": 494,
"offsetInEndSection": 539,
"text": "and N-, K-, and H-RAS (codons 12, 13, and 61)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17638058",
"endSection": "abstract"
}
] |
57279ef20fd6f91b68000018 | Which intraflagellar transport (IFT) motor protein has been linked to human skeletal ciliopathies? | Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies | [
"24140113",
"25205765",
"25470043",
"24183451"
] | factoid | [
{
"offsetInBeginSection": 295,
"offsetInEndSection": 411,
"text": "Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25470043",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 147,
"text": "Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25205765",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 408,
"text": "Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 525,
"text": "Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24183451",
"endSection": "abstract"
},
{
"offsetInBeginSection": 408,
"offsetInEndSection": 656,
"text": "All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 148,
"text": "Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25205765",
"endSection": "abstract"
},
{
"offsetInBeginSection": 524,
"offsetInEndSection": 617,
"text": "Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24183451",
"endSection": "abstract"
},
{
"offsetInBeginSection": 161,
"offsetInEndSection": 408,
"text": "All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113",
"endSection": "abstract"
},
{
"offsetInBeginSection": 161,
"offsetInEndSection": 410,
"text": "All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113",
"endSection": "abstract"
},
{
"offsetInBeginSection": 295,
"offsetInEndSection": 413,
"text": "Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25470043",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25205765",
"endSection": "abstract"
},
{
"offsetInBeginSection": 433,
"offsetInEndSection": 527,
"text": "Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24183451",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 410,
"text": " Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113",
"endSection": "abstract"
},
{
"offsetInBeginSection": 162,
"offsetInEndSection": 525,
"text": "All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 243,
"text": " Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies. Here, we define for the first time the composition of the human cytoplasmic dynein-2 complex.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25205765",
"endSection": "abstract"
},
{
"offsetInBeginSection": 232,
"offsetInEndSection": 527,
"text": "The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24183451",
"endSection": "abstract"
},
{
"offsetInBeginSection": 162,
"offsetInEndSection": 410,
"text": "All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25205765",
"endSection": "abstract"
},
{
"offsetInBeginSection": 434,
"offsetInEndSection": 527,
"text": "Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24183451",
"endSection": "abstract"
}
] |
56c1f011ef6e394741000042 | What is the mechanism of action of ocrelizumab for treatment of multiple sclerosis? | Ocrelizumab is a cytolytic monoclonal antibody that binds CD20 antigen present of B cells. It is approved for treatment of multiple sclerosis. | [
"22047971",
"23609782",
"23448220",
"22229582",
"24444048",
"24494635",
"24832354",
"18951300",
"24090587",
"24579720",
"22766059",
"24251808",
"25732947",
"24707333",
"24032475",
"24928997",
"22171583",
"24001305",
"23208729",
"25296871"
] | summary | [
{
"offsetInBeginSection": 80,
"offsetInEndSection": 474,
"text": "Recent therapeutic advances include modifications to improve tolerability of existing products (e.g. interferon beta and glatiramer acetate), development of novel anti-neuroinflammatory medications (e.g. fingolimod, teriflunomide and dimethyl fumarate, daclizumab, alemtuzumab, ocrelizumab) and investigation of treatments in progressive MS (e.g. natalizumab, mastinib, natalizumab, siponimod).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24707333",
"endSection": "abstract"
},
{
"offsetInBeginSection": 630,
"offsetInEndSection": 772,
"text": "This review provides insights into clinical studies with the mAbs natalizumab, alemtuzumab, daclizumab, rituximab, ocrelizumab and ofatumumab.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24001305",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1123,
"offsetInEndSection": 1456,
"text": "Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24032475",
"endSection": "abstract"
},
{
"offsetInBeginSection": 675,
"offsetInEndSection": 940,
"text": "More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24444048",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 166,
"text": "In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24928997",
"endSection": "abstract"
},
{
"offsetInBeginSection": 491,
"offsetInEndSection": 738,
"text": "Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25732947",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1314,
"offsetInEndSection": 1538,
"text": " To reduce the risk of infusion reactions and improve long-term tolerability, the human-derived components of the antibody have been increased to form humanized or human monoclonal antibodies like ocrelizumab and ofatumumab.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25296871",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1062,
"offsetInEndSection": 1149,
"text": "Ocrelizumab will likely also be licensed as a second-line therapy in highly active MS. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24579720",
"endSection": "abstract"
},
{
"offsetInBeginSection": 372,
"offsetInEndSection": 814,
"text": "This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24251808",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1033,
"offsetInEndSection": 1579,
"text": "In this review, we further discuss evidence for B cell and Ig contribution to human MS and NMO pathogenesis, pro-inflammatory and regulatory B cell effector functions, impaired B cell immune tolerance, the B cell-fostering microenvironment in the CNS, and B cell-targeted therapeutic interventions for MS and NMO, including CD20 depletion (rituximab, ocrelizumab, and ofatumumab), anti-IL6-R (tocilizumab), complement-blocking (eculizumab), inhibitors of AQP4-Ig binding (aquaporumab, small molecular compounds), and BAFF/BAFF-R-targeting agents.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24832354",
"endSection": "abstract"
},
{
"offsetInBeginSection": 669,
"offsetInEndSection": 979,
"text": "The main efficacy and safety results of these drugs are reviewed in this paper. They can be classified into 2 groups: oral (fingolimod, laquinimod, teriflunomide, BG-12 [dimethyl fumarate], oral cladribine, dalfampridine) and monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22766059",
"endSection": "abstract"
},
{
"offsetInBeginSection": 700,
"offsetInEndSection": 883,
"text": "Daclizumab and ocrelizumab are monoclonal antibodies that have shown efficacy and acceptable safety profiles in phase 2 trials; both are under investigation in ongoing phase 3 trials.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24090587",
"endSection": "abstract"
},
{
"offsetInBeginSection": 408,
"offsetInEndSection": 585,
"text": " As such, humoral targeted immunotherapies that are being developed for MS are discussed herein: rituximab, ocrelizumab, and ofatumumab show promise as B-cell depleting agents. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23208729",
"endSection": "abstract"
},
{
"offsetInBeginSection": 889,
"offsetInEndSection": 1052,
"text": " The section on anti-CD20 antibodies reviews Phase II results on ocrelizumab and ofatumumab, and discusses current perspectives of these antibodies for MS therapy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23448220",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1655,
"offsetInEndSection": 1858,
"text": "Rituximab is unlikely to be developed further as its license will expire, but ocrelizumab, another monoclonal antibody directly targeting B cells, is currently in phase 2 development and looks promising.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23609782",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1228,
"offsetInEndSection": 1439,
"text": "In addition, oral laquinimod, several monoclonal antibodies (eg, alemtuzumab, daclizumab, and ocrelizumab), and other agents have shown preliminary beneficial results in relapsing MS in phase 3 clinical trials. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24494635",
"endSection": "abstract"
},
{
"offsetInBeginSection": 614,
"offsetInEndSection": 1010,
"text": "They can be categorized according to their mode of action into compounds targeting (i) leukocyte migration into the CNS (natalizumab); (ii) cytolytic antibodies (rituximab, ocrelizumab, ofatumumab, alemtuzumab); or (iii) antibodies and recombinant proteins targeting cytokines and chemokines and their receptors (daclizumab, ustekinumab, atacicept, tabalumab [Ly-2127399], secukinumab [AIN457]). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22171583",
"endSection": "abstract"
},
{
"offsetInBeginSection": 731,
"offsetInEndSection": 933,
"text": "The second concept is to deplete T cells and/or B cells from the peripheral circulation using highly specific monoclonal antibodies such as alemtuzumab (anti-CD52) or rituximab/ocrelizumab (anti-CD20). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22229582",
"endSection": "abstract"
},
{
"offsetInBeginSection": 936,
"offsetInEndSection": 1200,
"text": "More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24444048",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 218,
"text": "Biogen Idec Inc, Genentech Inc, Roche Holding AG and Chugai Pharmaceutical Co Ltd are developing ocrelizumab, a humanized mAb against CD20, for the potential treatment of inflammatory disorders and B-cell malignancies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18951300",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 109,
"text": "Ocrelizumab, a humanized monoclonal antibody against CD20 for inflammatory disorders and B-cell malignancies.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18951300",
"endSection": "title"
},
{
"offsetInBeginSection": 246,
"offsetInEndSection": 421,
"text": "We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22047971",
"endSection": "abstract"
},
{
"offsetInBeginSection": 84,
"offsetInEndSection": 260,
"text": "We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22047971",
"endSection": "abstract"
}
] |
56a8d660a17756b72f000006 | What is the link between Nonidet-40 (NP-40) and biotinylation? | 0.5% of the non-ionic detergent Nonidet-40 (NP-40) during cell lysis and nuclei isolation is sufficient to practically eliminate contamination by endogenous biotinylated carboxylases during purification of biotin tagged nuclear proteins. | [
"23500724"
] | factoid | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 122,
"text": "NP-40 reduces contamination by endogenous biotinylated carboxylases during purification of biotin tagged nuclear proteins.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23500724",
"endSection": "title"
},
{
"offsetInBeginSection": 345,
"offsetInEndSection": 630,
"text": "We show that the use of 0.5% of the non-ionic detergent Nonidet-40 (NP-40) during cell lysis and nuclei isolation is sufficient to practically eliminate contamination of nuclear extracts by carboxylases and to greatly reduce background signals in downstream mass spectrometric analyses",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23500724",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 631,
"text": "We describe here a simple procedure for greatly reducing contamination of nuclear extracts by naturally biotinylated cytoplasmic carboxylases, which represent a major source of non-specific background when employing BirA-mediated biotinylation tagging for the purification and characterization of nuclear protein complexes by mass spectrometry. We show that the use of 0.5% of the non-ionic detergent Nonidet-40 (NP-40) during cell lysis and nuclei isolation is sufficient to practically eliminate contamination of nuclear extracts by carboxylases and to greatly reduce background signals in downstream mass spectrometric analyses.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23500724",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 632,
"text": " We describe here a simple procedure for greatly reducing contamination of nuclear extracts by naturally biotinylated cytoplasmic carboxylases, which represent a major source of non-specific background when employing BirA-mediated biotinylation tagging for the purification and characterization of nuclear protein complexes by mass spectrometry. We show that the use of 0.5% of the non-ionic detergent Nonidet-40 (NP-40) during cell lysis and nuclei isolation is sufficient to practically eliminate contamination of nuclear extracts by carboxylases and to greatly reduce background signals in downstream mass spectrometric analyses.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23500724",
"endSection": "abstract"
}
] |
5353aedb288f4dae47000006 | Which is the transcript responsible for X-chromosome inactivation? | The long non- coding RNA Xist (X inactive specific transcript) | [
"23847260",
"24040022",
"21094887",
"22065773",
"12952890",
"21660507",
"21471966",
"9099757",
"16679409",
"9678349",
"16507360",
"9487391",
"7536936",
"8353487",
"9024780",
"11751274",
"12667455",
"22925639",
"16107314",
"21364561",
"21947263",
"22889989",
"17333537",
"23122604",
"23166390",
"15015744",
"23535403",
"19013827",
"10359800",
"9074937",
"10026129",
"20043281",
"21820484",
"23093590",
"11774371"
] | factoid | [
{
"offsetInBeginSection": 359,
"offsetInEndSection": 419,
"text": "Xist, a gene responsible for X chromosome inactivation (XCI)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22065773",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1422,
"offsetInEndSection": 1519,
"text": "X inactivation-specific transcript (XIST) is a long ncRNA that mediates X chromosome inactivation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21094887",
"endSection": "abstract"
},
{
"offsetInBeginSection": 200,
"offsetInEndSection": 329,
"text": "the X inactive specific transcript (Xist) gene, which is known now to represent the master switch locus regulating X inactivation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9487391",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 106,
"text": "IST, a long non-coding RNA, plays an important role in triggering X chromosome inactivation in eutherians",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24040022",
"endSection": "abstract"
},
{
"offsetInBeginSection": 208,
"offsetInEndSection": 260,
"text": "X inactive-specific transcript (XIST) gene in humans",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23847260",
"endSection": "abstract"
},
{
"offsetInBeginSection": 502,
"offsetInEndSection": 589,
"text": "Xist (X-inactive specific transcript) is a major effector of the X-inactivation process",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23535403",
"endSection": "abstract"
},
{
"offsetInBeginSection": 335,
"offsetInEndSection": 468,
"text": "efforts have been focused on the X inactive-specific transcript (Xist) locus, discovered to be the master regulator of X-inactivation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23166390",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1024,
"offsetInEndSection": 1069,
"text": "X-inactivation specific transcript (Xist) RNA",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23122604",
"endSection": "abstract"
},
{
"offsetInBeginSection": 4,
"offsetInEndSection": 193,
"text": "transcriptional silencing of one of the female X-chromosomes is a finely regulated process that requires accumulation in cis of the long non-coding RNA X-inactive-specific transcript (Xist)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23093590",
"endSection": "abstract"
},
{
"offsetInBeginSection": 185,
"offsetInEndSection": 331,
"text": "the X-inactivated-specific transcript (Xist) gene, whose gene product consists of RNA which coats and thereby inactivates one of the X chromosomes",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22925639",
"endSection": "abstract"
},
{
"offsetInBeginSection": 113,
"offsetInEndSection": 255,
"text": "the X inactivation center (Xic). Xic contains many of the regulatory elements for the mutual interplay of X-inactive specific transcript (Xist",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22889989",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2,
"offsetInEndSection": 120,
"text": "chromosome inactivation (XCI) in female mammals depends on the noncoding RNA X inactivation specific transcript (Xist)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947263",
"endSection": "abstract"
},
{
"offsetInBeginSection": 177,
"offsetInEndSection": 371,
"text": " One of the striking features that characterize the Xic landscape is the abundance of loci transcribing non-coding RNAs (ncRNAs), including Xist, the master regulator of the inactivation process",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21820484",
"endSection": "abstract"
},
{
"offsetInBeginSection": 160,
"offsetInEndSection": 352,
"text": "The process is mediated by the non-coding RNA X inactive specific transcript (Xist) that binds in cis and propagates along the inactive X chromosome elect, triggering chromosome-wide silencing",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21660507",
"endSection": "abstract"
},
{
"offsetInBeginSection": 217,
"offsetInEndSection": 387,
"text": "the X chromosome of paternal origin (Xp) is silenced during early embryogenesis owing to imprinted expression of the regulatory RNA, Xist (X-inactive specific transcript)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21471966",
"endSection": "abstract"
},
{
"offsetInBeginSection": 599,
"offsetInEndSection": 642,
"text": "X-inactive-specific transcript (Xist) gene ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21364561",
"endSection": "abstract"
},
{
"offsetInBeginSection": 511,
"offsetInEndSection": 675,
"text": "expression of the non-coding X-inactive specific transcript (Xist) RNA and depends on specific cellular contexts, in which essential silencing factors are expressed",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20043281",
"endSection": "abstract"
},
{
"offsetInBeginSection": 339,
"offsetInEndSection": 432,
"text": "Xist (X-inactive specific transcript) and Tsix gene pair, which is pivotal in X-inactivation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19013827",
"endSection": "abstract"
},
{
"offsetInBeginSection": 166,
"offsetInEndSection": 359,
"text": "In eutherian mammals X inactivation is regulated by the X-inactive specific transcript (Xist), a cis-acting non-coding RNA that triggers silencing of the chromosome from which it is transcribed",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17333537",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 176,
"text": " inactivation in female mammals involves transcriptional silencing of an entire chromosome in response to a cis-acting noncoding RNA, the X inactive-specific transcript (Xist)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16679409",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2,
"offsetInEndSection": 92,
"text": "chromosome inactivation (XCI) depends on a noncoding sense-antisense transcript pair, Xist",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16507360",
"endSection": "abstract"
},
{
"offsetInBeginSection": 143,
"offsetInEndSection": 217,
"text": " The key regulatory molecule that triggers silencing is the Xist transcrip",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16107314",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2,
"offsetInEndSection": 216,
"text": "chromosome inactivation begins when a novel chromosomal RNA (cRNA) from the imprinted mouse Xist or human XIST locus coats or \"paints\" one X chromosome in cis and initiates a cascade of chromosome remodeling events",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15015744",
"endSection": "abstract"
},
{
"offsetInBeginSection": 4,
"offsetInEndSection": 122,
"text": "X-inactive-specific transcript (Xist) locus is a cis-acting switch that regulates X chromosome inactivation in mammals",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12952890",
"endSection": "abstract"
},
{
"offsetInBeginSection": 66,
"offsetInEndSection": 220,
"text": " In X chromosome inactivation (XCI), unfavorable XCI ratios promote X-linked disease penetrance in females. During XCI, one X is randomly silenced by Xist",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12667455",
"endSection": "abstract"
},
{
"offsetInBeginSection": 3,
"offsetInEndSection": 121,
"text": " imprinted mouse Xist (X-inactive specific transcript) gene is involved in the initiation of X-chromosome inactivation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11774371",
"endSection": "abstract"
},
{
"offsetInBeginSection": 85,
"offsetInEndSection": 212,
"text": "initiation of X-chromosome inactivation are critically dependent on the expression of the X-inactive specific transcript (Xist)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11751274",
"endSection": "abstract"
},
{
"offsetInBeginSection": 14,
"offsetInEndSection": 178,
"text": "X chromosome inactivation requires the presence, in cis, of the X inactivation center (XIC). The Xist gene, which lies within the XIC region in both human and mouse",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10359800",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2,
"offsetInEndSection": 36,
"text": "inactive-specific transcript (Xist",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10026129",
"endSection": "title"
},
{
"offsetInBeginSection": 17,
"offsetInEndSection": 187,
"text": " X inactive-specific transcript (Xist) is thought to be essential for the initiation of X chromosome inactivation and dosage compensation during female embryo development",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10026129",
"endSection": "abstract"
},
{
"offsetInBeginSection": 427,
"offsetInEndSection": 574,
"text": "deletions of the X inactivation center (XIC/Xic) and/or the X inactive specific transcript (XIST/Xist) gene result in failure of cis X-inactivation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9678349",
"endSection": "abstract"
},
{
"offsetInBeginSection": 4,
"offsetInEndSection": 100,
"text": "Xist (X inactive specific transcript) gene plays an essential role in X chromosome inactivation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9099757",
"endSection": "abstract"
},
{
"offsetInBeginSection": 994,
"offsetInEndSection": 1086,
"text": "expression of the Xist (X inactive specific transcript) gene correlates with X inactivation ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9074937",
"endSection": "abstract"
},
{
"offsetInBeginSection": 820,
"offsetInEndSection": 863,
"text": "XIST (X inactive specific transcript) gene ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9024780",
"endSection": "abstract"
},
{
"offsetInBeginSection": 38,
"offsetInEndSection": 355,
"text": "one of the two X chromosomes in somatic cells of the female becomes inactivated through a process that is thought to depend on a unique initiator region, the X-chromosome inactivation center (Xic). The recently characterized Xist sequence (X-inactive-specific transcript) is thought to be a possible candidate for Xic",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7536936",
"endSection": "abstract"
},
{
"offsetInBeginSection": 4,
"offsetInEndSection": 73,
"text": "human XIST gene, a candidate for a role in X chromosome inactivation,",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8353487",
"endSection": "abstract"
}
] |
56e0813651531f7e33000010 | What are viral vectors used for in optogenetics? | Viral vectors are used to express optogenetic constructs in selected cells. | [
"23283335",
"21041318",
"25352792",
"24647936",
"22341326",
"23724838",
"23217739",
"25070340",
"23877069",
"24572099",
"23088961",
"25954011",
"21278729",
"24001071",
"23044043",
"21373649",
"22341319",
"22890236",
"24285886",
"24048849",
"25741722",
"25759964",
"21782903"
] | summary | [
{
"offsetInBeginSection": 1342,
"offsetInEndSection": 1580,
"text": "To express ChR in neurons, the common expression systems include viral vectors, in utero electroporation, and transgenic animals, each with their advantages and limitations regarding the cost, expression pattern, and the required effort. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22341319",
"endSection": "abstract"
},
{
"offsetInBeginSection": 472,
"offsetInEndSection": 744,
"text": "In this review, the various strategies for selective genetic targeting of a defined neuronal population are discussed as well as the pros and cons of the use of transgenic animals and recombinant viral vectors for the expression of transgenes in a specific set of neurons.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22341326",
"endSection": "abstract"
},
{
"offsetInBeginSection": 251,
"offsetInEndSection": 451,
"text": "We demonstrate how the ability to target astrocytes with cell-specific viral vectors to express optogenetic constructs helped to unravel some previously unsuspected roles of these inconspicuous cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21041318",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 169,
"text": "Optogenetics, the use of light to stimulate or inhibit neural circuits via viral transduction of protein channels, has emerged as a possible method of treating epilepsy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23724838",
"endSection": "abstract"
},
{
"offsetInBeginSection": 449,
"offsetInEndSection": 649,
"text": "We demonstrate how the ability to target astrocytes with cell-specific viral vectors to express optogenetic constructs helped to unravel some previously unsuspected roles of these inconspicuous cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21041318",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1644,
"offsetInEndSection": 1833,
"text": "We conclude that a viral vector approach with a strong promoter is required for successful optogenetic stimulation of distal axons to evoke transmitter release in pre-autonomic PVN neurons.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22890236",
"endSection": "abstract"
},
{
"offsetInBeginSection": 788,
"offsetInEndSection": 1169,
"text": "RESULTS: Extracellular single-unit recordings were made from infralimbic (IL) pyramidal cells, IL interneurons and prelimbic (PL) pyramidal cells 2-3 weeks after intra-IL injection of a viral vector encoding channel rhodopsin 2 (ChR2) under the control of the CaMKII promoter (rAAV5/CaMKIIa-ChR2(H134R)-EYFP) or a control vector that lacked the ChR2 sequence (rAAV5/CaMKIIa-EYFP). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23044043",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1461,
"offsetInEndSection": 1651,
"text": "We conclude that a viral vector approach with a strong promoter is required for successful optogenetic stimulation of distal axons to evoke transmitter release in pre-autonomic PVN neurons. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22890236",
"endSection": "abstract"
},
{
"offsetInBeginSection": 554,
"offsetInEndSection": 756,
"text": "We selectively expressed ChR2(H134R) in rostral VLM catecholaminergic neurons by injecting Cre-dependent adeno-associated viral vectors into the brain of adult dopamine-β-hydroxylase (DβH)(Cre/0) mice. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24285886",
"endSection": "abstract"
},
{
"offsetInBeginSection": 412,
"offsetInEndSection": 848,
"text": "We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25741722",
"endSection": "abstract"
},
{
"offsetInBeginSection": 448,
"offsetInEndSection": 695,
"text": "We generated rabies glycoprotein-pseudotyped lentiviral vectors that use a positive feedback loop composed of a Tet promoter driving both its own tetracycline-dependent transcription activator (tTA) (\"TLoop\") and channelrhodopsin-2-YFP (ChR2YFP). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24572099",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 57,
"text": "Optogenetic control of cardiomyocytes via viral delivery.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25070340",
"endSection": "title"
},
{
"offsetInBeginSection": 350,
"offsetInEndSection": 577,
"text": "Here, we used an optogenetic approach, in which female rats received bilateral dorsal mPFC microinjections of viral constructs coding light-sensitive eNpHR3.0-eYFP or control eYFP protein and intracranial fiber optic implants. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23283335",
"endSection": "abstract"
},
{
"offsetInBeginSection": 277,
"offsetInEndSection": 417,
"text": "We transduced rat LC neurons by direct injection of a lentiviral vector expressing channelrhodopsin2 under the control of the PRS promoter. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24647936",
"endSection": "abstract"
},
{
"offsetInBeginSection": 142,
"offsetInEndSection": 321,
"text": "Here, we describe the construction of a blue-light-induced K(+) channel 1 (BLINK1) engineered by fusing the plant LOV2-J� photosensory module to the small viral K(+) channel Kcv. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25954011",
"endSection": "abstract"
},
{
"offsetInBeginSection": 500,
"offsetInEndSection": 908,
"text": "In parallel, remarkable success in the development of highly efficient viral vectors for ocular gene therapy led to new strategies of using these novel optogenetic tools for vision restoration. These recent findings show that novel optogenetic tools and viral vectors for ocular gene delivery are now available providing many opportunities to develop potential optogenetic strategies for vision restoration.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25759964",
"endSection": "abstract"
}
] |
56c83f365795f9a73e000011 | Which domain allowing self-association do exist in TDP-43 and FUS proteins? | PRION PROTEINS | [
"24842888",
"20356930",
"10521526",
"22454397",
"22065782",
"23629963",
"24920338",
"21327870",
"25002999",
"22445064",
"24262168",
"21844169",
"22563080",
"20720006"
] | factoid | [
{
"offsetInBeginSection": 288,
"offsetInEndSection": 873,
"text": "Using transient expression of a panel of deletion and chimeric FUS variants in various cultured cells, we demonstrated that FUS accumulating in the cytoplasm nucleates a novel type of RNA granules, FUS granules (FGs), that are structurally similar but not identical to physiological RNA transport granules. Formation of FGs requires FUS N-terminal prion-like domain and the ability to bind specific RNAs. Clustering of FGs coupled with further recruitment of RNA and proteins produce larger structures, FUS aggregates (FAs), that resemble but are clearly distinct from stress granules.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24842888",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 620,
"text": "Approximately 1% of human proteins harbor a prion-like domain (PrLD) of similar low complexity sequence and amino acid composition to domains that drive prionogenesis of yeast proteins like Sup35. PrLDs are over-represented in human RNA-binding proteins and mediate phase transitions underpinning RNP granule assembly. This modality renders PrLDs prone to misfold into conformers that accrue in pathological inclusions that characterize various fatal neurodegenerative diseases. For example, TDP-43 and FUS form cytoplasmic inclusions in amyotrophic lateral sclerosis (ALS) and mutations in TDP-43 and FUS can cause ALS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25002999",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1328,
"offsetInEndSection": 1534,
"text": "FUS and TDP-43, which rank 1st and 10th among RRM-bearing prion candidates, form cytoplasmic inclusions in the degenerating motor neurons of ALS patients and mutations in TDP-43 and FUS cause familial ALS. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22445064",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 221,
"text": "Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22065782",
"endSection": "abstract"
},
{
"offsetInBeginSection": 601,
"offsetInEndSection": 790,
"text": "two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20356930",
"endSection": "abstract"
},
{
"offsetInBeginSection": 98,
"offsetInEndSection": 411,
"text": "Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15 have been connected to ALS. These three proteins share several features, including the presence of a bioinformatics-predicted prion domain, aggregation-prone nature in vitro and in vivo and toxic effects when expressed in multiple model systems.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22454397",
"endSection": "abstract"
},
{
"offsetInBeginSection": 591,
"offsetInEndSection": 789,
"text": "Moreover, two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20356930",
"endSection": "abstract"
},
{
"offsetInBeginSection": 294,
"offsetInEndSection": 440,
"text": "TDP-43 and FUS and several related RNA-binding proteins harbor aggregation-promoting prion-like domains that allow them to rapidly self-associate.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23629963",
"endSection": "abstract"
},
{
"offsetInBeginSection": 486,
"offsetInEndSection": 705,
"text": "Molecular cloning of subunit 4 of the complex revealed that it is a proteasome-COP9 complex-eIF3 domain protein encoded by a gene that maps to chromosome 5, near the chromosomal location of the cop8 and fus4 mutations. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10521526",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1184,
"offsetInEndSection": 1328,
"text": "Deletions in the C-terminal domain of TDP-43 that preclude interactions with hnRNP A2/B1 abolish TDP-43-dependent rescue of CGG repeat toxicity.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24920338",
"endSection": "abstract"
},
{
"offsetInBeginSection": 745,
"offsetInEndSection": 897,
"text": "The rescue appears specific to TDP-43, as co-expression of another ALS-associated RNA-binding protein, FUS, exacerbates the toxic effects of CGG repeats",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24920338",
"endSection": "abstract"
},
{
"offsetInBeginSection": 209,
"offsetInEndSection": 455,
"text": "Recently, through Next-Generation Exome sequencing approaches a mutation resulting in a substitution (p.Q290X) in the nuclear export domain of the FUS protein was nominated as a cause of autosomal dominant essential tremor (ET) in a large kindred",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24262168",
"endSection": "abstract"
},
{
"offsetInBeginSection": 547,
"offsetInEndSection": 602,
"text": "TDP-43 is another RNA-binding protein implicated in ALS",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24262168",
"endSection": "abstract"
},
{
"offsetInBeginSection": 947,
"offsetInEndSection": 1183,
"text": "We also provide multiple independent lines of in vitro and in vivo evidence that EWSR1 has similar properties as TDP-43, FUS and TAF15, including aggregation-prone behavior in vitro and ability to confer neurodegeneration in Drosophila.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22454397",
"endSection": "abstract"
},
{
"offsetInBeginSection": 876,
"offsetInEndSection": 974,
"text": "For TDP-43, both the RRM1 and the C-terminal glycine-rich domain are required for SG localization.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22563080",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1628,
"offsetInEndSection": 1733,
"text": "Furthermore, TDP-43 and FUS display distinct domain requirements in aggregate formation and cytotoxicity.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21327870",
"endSection": "abstract"
},
{
"offsetInBeginSection": 672,
"offsetInEndSection": 878,
"text": "Binding was mediated by an unstructured TDP-43 C-terminal domain and occurred within the context of a 300-400-kDa complex that also contained C-terminal cleavage products of TDP-43 linked to neuropathology.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20720006",
"endSection": "abstract"
},
{
"offsetInBeginSection": 121,
"offsetInEndSection": 330,
"text": "It was recently found that dominant mutations in two related RNA-binding proteins, TDP-43 (43-kDa TAR DNA-binding domain protein) and FUS/TLS (fused in sarcoma/translated in liposarcoma) cause a subset of ALS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20720006",
"endSection": "abstract"
}
] |
5545dc7de233d84047000001 | Is there a role for transcription factories in genome organization? | The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. There may be certain efficiency benefits to cluster transcriptional activity in this way. However, the clustering of genes at transcription factories may have consequences for genome stability, and increase the susceptibility to recurrent chromosomal translocations that lead to cancer | [
"24003126",
"24166911",
"16500976",
"21880598",
"19506577",
"17913488",
"20074071"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 777,
"text": "The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. There may be certain efficiency benefits to cluster transcriptional activity in this way. However, the clustering of genes at transcription factories may have consequences for genome stability, and increase the susceptibility to recurrent chromosomal translocations that lead to cancer",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24166911",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 75,
"text": "In the eukaryotic nucleus, genes are transcribed in transcription factories",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21880598",
"endSection": "abstract"
},
{
"offsetInBeginSection": 192,
"offsetInEndSection": 756,
"text": "Based on this analysis, we propose that transcription factories result from the aggregation of RNA polymerase II-containing pre-initiation complexes assembled next to each other in the nuclear space. Such an aggregation can be triggered by the phosphorylation of the C-terminal domain of RNA polymerase II molecules and their interaction with various transcription factors. Individual transcription factories would thus incorporate tissue-specific, co-regulated as well as housekeeping genes based only on their initial proximity to each other in the nuclear space",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21880598",
"endSection": "abstract"
},
{
"offsetInBeginSection": 453,
"offsetInEndSection": 794,
"text": "active polymerases cluster into replication and transcription \"factories\" in both pro- and eukaryotes. We conclude that the second law of thermodynamics acts through nonspecific entropic forces between engaged polymerases to drive the self-organization of genomes into loops containing several thousands (and sometimes millions) of basepairs",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16500976",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 291,
"text": "Since the advent of FISH (fluorescence in situ hybridization), there have been major advances in our understanding of how the genome is organized in interphase nuclei. Indeed, this organization is found to be non-random and individual chromosomes occupy discrete regions known as territories",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20074071",
"endSection": "abstract"
},
{
"offsetInBeginSection": 419,
"offsetInEndSection": 663,
"text": " in proliferating cells, there is evidently a correlation between radial positioning and gene density. Indeed, gene-poor chromosomes tend to be located towards the nuclear edge, while those that are more gene-rich are positioned more internally",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20074071",
"endSection": "abstract"
},
{
"offsetInBeginSection": 488,
"offsetInEndSection": 593,
"text": "Recently described active chromatin hubs and transcription factories also involve long-range interactions",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17913488",
"endSection": "abstract"
},
{
"offsetInBeginSection": 610,
"offsetInEndSection": 825,
"text": "The transcription factory model has implications for the regulation of transcription initiation and elongation, for the organization of genes in the genome, for the co-regulation of genes and for genome instability.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19506577",
"endSection": "abstract"
}
] |
531778ddb166e2b80600000f | Which are the Chompret criteria for Li-Fraumeni syndrome? | 1) According to the Chompret criteria for LFS, any patient with adrenocortical cancer (ACC), irrespective of age and family history, is at high risk for a TP53 germline mutation.
2) All families with a p53 mutation must have at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma (ACC). | [
"22170717",
"19204208"
] | list | [
{
"offsetInBeginSection": 116,
"offsetInEndSection": 292,
"text": "According to the Chompret criteria for LFS, any patient with adrenocortical cancer (ACC), irrespective of age and family history, is at high risk for a TP53 germline mutation. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22170717",
"endSection": "abstract"
},
{
"offsetInBeginSection": 725,
"offsetInEndSection": 854,
"text": "All families with a p53 mutation had at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma (ACC).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19204208",
"endSection": "abstract"
}
] |
56d042ae3975bb303a00000d | When ceritinib used instead of crizotinib? | Ceritinib is approved for the treatment of ALK-positive metastatic NSCLC patients that are crizotinib-resistant and crizotinib-naïve. | [
"24675041",
"24891360",
"25945060",
"25101329",
"26366094",
"24856155",
"24670165",
"25458559",
"25258420"
] | list | [
{
"offsetInBeginSection": 840,
"offsetInEndSection": 1010,
"text": "Ceritinib is a second-generation ALK inhibitor that has demonstrated activity in crizotinib-resistant patients, becoming a promising treatment option in this population. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25945060",
"endSection": "abstract"
},
{
"offsetInBeginSection": 424,
"offsetInEndSection": 583,
"text": "Ceritinib is approved for the treatment of ALK-positive metastatic NSCLC in patients who are intolerant to or have progressed despite therapy with crizotinib. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25258420",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1408,
"offsetInEndSection": 1547,
"text": "Ceritinib has activity in crizotinib-resistant and crizotinib-naïve patients and appears to be a viable alternative for ALK-positive NSCLC.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25258420",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1312,
"offsetInEndSection": 1985,
"text": "In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25458559",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1215,
"offsetInEndSection": 1415,
"text": "Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041",
"endSection": "abstract"
},
{
"offsetInBeginSection": 997,
"offsetInEndSection": 1191,
"text": "Preclinical data showed impressive antitumor activity against crizotinib-resistant clones, and based on available data, ceritinib could represent a suitable option in crizotinib-resistant NSCLC.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25101329",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 90,
"text": "The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 101,
"text": "Ceritinib (LDK378): a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25458559",
"endSection": "title"
},
{
"offsetInBeginSection": 805,
"offsetInEndSection": 1611,
"text": "However, we observed that ceritinib did not overcome two crizotinib-resistant ALK mutations, G1202R and F1174C, and one of these mutations was identified in 5 of 11 biopsies from patients with acquired resistance to ceritinib. Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease.SIGNIFICANCE: The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib. These findings provide the molecular basis for the marked clinical activity of ceritinib in patients with ALK-positive NSCLC with crizotinib-resistant disease. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041",
"endSection": "abstract"
},
{
"offsetInBeginSection": 794,
"offsetInEndSection": 1221,
"text": "However, we observed that ceritinib did not overcome two crizotinib-resistant ALK mutations, G1202R and F1174C, and one of these mutations was identified in 5 of 11 biopsies from patients with acquired resistance to ceritinib. Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1021,
"offsetInEndSection": 1427,
"text": "Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease. The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041",
"endSection": "abstract"
},
{
"offsetInBeginSection": 330,
"offsetInEndSection": 1316,
"text": "The accelerated approval of potent ALK inhibitors, such as crizotinib and more recently ceritinib (LDK378), based on the well designed phase I/II trials has been a landmark success in clinical cancer research and contributes a new era of oncogenic targeted therapy characterized by elegant clinical trial design. In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25458559",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1222,
"offsetInEndSection": 1587,
"text": "The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib. These findings provide the molecular basis for the marked clinical activity of ceritinib in patients with ALK-positive NSCLC with crizotinib-resistant disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041",
"endSection": "abstract"
},
{
"offsetInBeginSection": 643,
"offsetInEndSection": 1348,
"text": "In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented. Copyright © 2015 Elsevier Inc.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25458559",
"endSection": "abstract"
}
] |
52bf1f1303868f1b06000014 | What type of enzyme is peroxiredoxin 2 (PRDX2)? | Peroxiredoxin 2 (PRDX2) is an antioxidant enzyme that uses cysteine residues to decompose peroxides.
Peroxiredoxin-2 (PRDX2), an enzyme reducing hydrogen peroxide and lipid peroxides
Peroxiredoxin 2 (Prx2) is a thiol-dependent peroxidase. | [
"12943237",
"19969073",
"22989627",
"18479207",
"20646000",
"21248284",
"21902453",
"17522089",
"23889121",
"23749642",
"21083423",
"18222042",
"22916248",
"19812325",
"17105810",
"19375361"
] | factoid | [
{
"offsetInBeginSection": 11,
"offsetInEndSection": 108,
"text": "Peroxiredoxin-2 (PRDX-2) is an antioxidant and chaperone-like protein critical for cell function.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23889121",
"endSection": "abstract"
},
{
"offsetInBeginSection": 215,
"offsetInEndSection": 349,
"text": "We found that the antioxidant enzyme peroxiredoxin-2 (Prx2) inversely correlated with the metastatic capacity of human melanoma cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23749642",
"endSection": "abstract"
},
{
"offsetInBeginSection": 51,
"offsetInEndSection": 248,
"text": "The aim of this study was to examine gonadotropin regulation of antioxidant enzyme sulfiredoxin (Srx) and peroxiredoxin 2 (PRDX2) expressions and modification during the ovulatory process in rats. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22989627",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1167,
"offsetInEndSection": 1392,
"text": "The mRNA profiler array showed more than 2-fold differential expression of 32 oxidative stress-related genes in unstimulated moDCs, including peroxiredoxin-2 (PRDX2), an enzyme reducing hydrogen peroxide and lipid peroxides. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22916248",
"endSection": "abstract"
},
{
"offsetInBeginSection": 159,
"offsetInEndSection": 254,
"text": "Peroxiredoxin-2 (Prx-2) is an abundant mammalian enzyme that protects against oxidative stress.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21902453",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 123,
"text": "Peroxiredoxin 2 (PRDX2) has been known to act as an antioxidant enzyme whose main function is H(2)O(2) reduction in cells. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21248284",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1067,
"offsetInEndSection": 1347,
"text": "These data indicate that Srx1 activity protects mice from the lethality of endotoxic shock, adding this enzyme to other host factors, as NRF2 and peroxiredoxin 2, which by regulating cellular reactive oxygen species levels act as important modifiers in the pathogenesis of sepsis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21083423",
"endSection": "abstract"
},
{
"offsetInBeginSection": 639,
"offsetInEndSection": 722,
"text": "One of the identified proteins was peroxiredoxin 2 (Prx2), an anti-oxidant enzyme. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20646000",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 185,
"text": "Peroxiredoxin-2 (Prdx2), a potent peroxide reductant, is the third most abundant protein in the erythrocyte and might be expected to play a major role in the cell's oxidative defenses. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19969073",
"endSection": "abstract"
},
{
"offsetInBeginSection": 819,
"offsetInEndSection": 940,
"text": "Importantly, we also demonstrate the antioxidant enzyme Prx2 (peroxiredoxin 2) as a critical cytoplasmic target of cdk5. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19812325",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 143,
"text": "Human erythrocyte peroxiredoxin 2 (Prx2) is a typical 2-cys cytosolic peroxiredoxin with thiol-dependent hydrogen peroxide scavenger activity. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19375361",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 99,
"text": "Peroxiredoxin 2 (Prx2) is an antioxidant enzyme that uses cysteine residues to decompose peroxides.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18479207",
"endSection": "abstract"
},
{
"offsetInBeginSection": 860,
"offsetInEndSection": 1077,
"text": "Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, was the most upregulated while tribbles homolog 3 (TRB3), a pro-apoptotic protein, was the most downregulated, implying a beneficial effect of lithium on neuronal cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18222042",
"endSection": "abstract"
},
{
"offsetInBeginSection": 204,
"offsetInEndSection": 352,
"text": "After 5 Gy irradiation, the relative abundance of peroxiredoxin 2, an antioxidant enzyme, and latexin, an inhibitor of carboxypeptidase, increased. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17522089",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 175,
"text": "Peroxiredoxin 2 (Prx2), a thiol-dependent peroxidase, is the third most abundant protein in the erythrocyte, and its absence in knock-out mice gives rise to hemolytic anemia. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17105810",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 340,
"text": "Suppression subtractive hybridization performed on Down syndrome (DS) versus control fetal brains revealed differential expression of peroxiredoxin 2 (PRDX2), mapped at 13q12. Peroxiredoxins are antioxidant enzymes involved in protein and lipid protection against oxidative injury and in cellular signalling pathways regulating apoptosis. T",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12943237",
"endSection": "abstract"
}
] |
52f20d802059c6d71c00000a | Is the length of the poly(A) tail involved in human disease? | Yes. Severely truncated poly(A) tails of mitochondrial mRNAs were found to be involved in an autosomal recessive spastic ataxia with optic atrophy. | [
"20970105"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 518,
"text": "In human mitochondria, polyadenylation of mRNA, undertaken by the nuclear-encoded mitochondrial poly(A) RNA polymerase, is essential for maintaining mitochondrial gene expression. Our molecular investigation of an autosomal-recessive spastic ataxia with optic atrophy, present among the Old Order Amish, identified a mutation of MTPAP associated with the disease phenotype. When subjected to poly(A) tail-length assays, mitochondrial mRNAs from affected individuals were shown to have severely truncated poly(A) tails.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20970105",
"endSection": "abstract"
}
] |
53355714d6d3ac6a34000045 | Why graphics processing units (GPU) are more suitable for biological tasks than central processing units (CPU)? | Traditional central processing unist (CPUs) are reaching their limit in processing power and are not designed primarily for multithreaded applications. Graphics processing units (GPUs) on the other hand are affordable, scalable computer powerhouses that, thanks to the ever increasing demand for higher quality graphics, have yet to reach their limit. Typically high-end CPUs have 8-16 cores, whereas GPUs can have more than 2,500 cores. GPUs are also, by design, highly parallel, multicore and multithreaded, able of handling thousands of threads doing the same calculation on different subsets of a large data set. This ability is what makes them perfectly suited for biological analysis tasks. Lately this potential has been realized by many bioinformatics researches and a huge variety of tools and algorithms have been ported to GPUs, or designed from the ground up to maximize the usage
of available cores. | [
"18070356",
"22759575",
"18061402",
"20715052",
"23391255",
"22537298",
"21357575",
"22149859",
"23281733",
"20589122",
"20357844"
] | summary | [
{
"offsetInBeginSection": 759,
"offsetInEndSection": 995,
"text": "The global speedups of 22.11, 38.80, and 44.80 are found comparing the parallel computation of one GPU, two GPUs by exact rotational operator, and two GPU versions by an approximate rotational operator with serial computation of the CPU",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23391255",
"endSection": "abstract"
},
{
"offsetInBeginSection": 3,
"offsetInEndSection": 195,
"text": "evaluate the use of general-purpose graphics processing units (GPGPUs) to improve the performance of MODFLOW, an unstructured preconditioned conjugate gradient (UPCG) solver has been developed",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23281733",
"endSection": "abstract"
},
{
"offsetInBeginSection": 201,
"offsetInEndSection": 541,
"text": "UPCG solver uses a compressed sparse row storage scheme and includes Jacobi, zero fill-in incomplete, and modified-incomplete lower-upper (LU) factorization, and generalized least-squares polynomial preconditioners. The UPCG solver also includes options for sequential and parallel solution on the central processing unit (CPU) using OpenMP",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23281733",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1052,
"offsetInEndSection": 1544,
"text": "Testing indicates GPGPU speedups on the order of 2 to 8, relative to the standard MODFLOW preconditioned conjugate gradient (PCG) solver, can be achieved when (1) memory copies between the CPU and GPGPU are optimized, (2) the percentage of time performing memory copies between the CPU and GPGPU is small relative to the calculation time, (3) high-performance GPGPU cards are utilized, and (4) CPU-GPGPU combinations are used to execute sequential operations that are difficult to parallelize",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23281733",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2052,
"offsetInEndSection": 2305,
"text": "A list-mode ToF OSEM library was developed on the GPU-CUDA platform. Our studies show that the GPU reformulation is considerably faster than a single-threaded reference CPU method especially for ToF processing, while producing virtually identical images",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22149859",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1253,
"offsetInEndSection": 1420,
"text": "When applied to line projection operations for non-ToF list-mode PET, this new GPU-CUDA method is >200 times faster than a single-threaded reference CPU implementation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22149859",
"endSection": "abstract"
},
{
"offsetInBeginSection": 564,
"offsetInEndSection": 841,
"text": "The GPU-based parallel implementation of the Gillespie stochastic simulation algorithm (SSA), the logarithmic direct method (LDM) and the next reaction method (NRM) is approximately 85 times faster than the sequential implementation of the NRM on a central processing unit (CPU",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21357575",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 296,
"text": "exploration of fundamental biological processes involving the forced unraveling of multimeric proteins, the sliding motion in protein fibers and the mechanical deformation of biomolecular assemblies under physiological force loads is challenging even for distributed computing systems",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20715052",
"endSection": "abstract"
},
{
"offsetInBeginSection": 468,
"offsetInEndSection": 692,
"text": "We assessed the computational performance of an end-to-end application of the program, where all the steps of the algorithm are running on a GPU, by profiling the simulation time and memory usage for a number of test systems",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20715052",
"endSection": "abstract"
},
{
"offsetInBeginSection": 754,
"offsetInEndSection": 847,
"text": "Our results show that the GPGPUs can provide significant speedup over conventional processors",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20357844",
"endSection": "abstract"
},
{
"offsetInBeginSection": 17,
"offsetInEndSection": 207,
"text": "explore the power and feasibility of using programmable graphics processing units (GPUs) for real-time rendering and displaying large 3D medical datasets for stereoscopic display workstation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18061402",
"endSection": "abstract"
},
{
"offsetInBeginSection": 401,
"offsetInEndSection": 691,
"text": "The performance of rendering and displaying was measured and compared between GPU-based and central processing unit (CPU)-based programming. The results indicate that GPU-based programming was capable of rendering large 3D datasets at real-time interactive rates with stereographic displays",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18061402",
"endSection": "abstract"
}
] |
52fb42752059c6d71c00005e | Which are the thyroid hormone analogs utilized in human studies? | TRIAC and TETRAC are two different thyroid hormone analogs utilized in human studies | [
"18954857",
"20187783",
"22947347",
"7608251",
"18080776",
"16384862",
"19903697",
"23970761",
"23307789",
"22123068",
"3730832",
"1193013",
"9001190",
"23298477",
"18386142",
"23565368",
"21896621"
] | list | [
{
"offsetInBeginSection": 273,
"offsetInEndSection": 427,
"text": "Here, we evaluate the therapeutic potential of the TH analog 3,5,3',5'-tetraiodothyroacetic acid (tetrac) as a replacement for T(4) in brain development. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23307789",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1104,
"offsetInEndSection": 1296,
"text": "This treatment was sufficient to promote TH-dependent neuronal differentiation in the cerebellum, cerebral cortex, and striatum but was ineffective in suppressing hypothalamic TRH expression. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23307789",
"endSection": "abstract"
},
{
"offsetInBeginSection": 347,
"offsetInEndSection": 620,
"text": "In the current study, we investigated the effect of a natural thyroid hormone analogue - 3, 3?, 5-triiodo-thyroacetic acid (TRIAC) on regulating proliferation and differentiation and its possible molecular mechanism in normal human epidermal keratinocytes and C57BL/6 mice.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23298477",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1241,
"offsetInEndSection": 1369,
"text": "TRIAC was effective and safe in ameliorating the effects of hyperthyroidism and ADHD symptoms in a child with known genetic RTH.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22947347",
"endSection": "abstract"
}
] |
532f0c4ed6d3ac6a3400002e | Are patients with marfan syndrome at increased risk of arrhythmias? | Patients with marfan syndrome carry increased risk for arrhythmias | [
"17597390",
"22738784",
"12535830"
] | yesno | [
{
"offsetInBeginSection": 12,
"offsetInEndSection": 183,
"text": "Marfan syndrome (MFS) is a variable, autosomal-dominant disorder of the connective tissue. In MFS serious ventricular arrhythmias and sudden cardiac death (SCD) can occur.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22738784",
"endSection": "abstract"
},
{
"offsetInBeginSection": 127,
"offsetInEndSection": 191,
"text": "Marfan's patients carry increased risk for cardiac arrhythmias. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17597390",
"endSection": "abstract"
},
{
"offsetInBeginSection": 774,
"offsetInEndSection": 935,
"text": "Ventricular arrhythmias were present in 21% and were associated with increased left ventricular size, mitral valve prolapse, and abnormalities of repolarization.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12535830",
"endSection": "abstract"
},
{
"offsetInBeginSection": 949,
"offsetInEndSection": 1277,
"text": "Cardiac complications are rare in young patients with Marfan syndrome receiving medical therapy and close clinical follow-up. Sudden death still occurs, and appears more common in patients with a dilated left ventricle. Left ventricular dilation may predispose to alterations of repolarization and fatal ventricular arrhythmias.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12535830",
"endSection": "abstract"
}
] |
5509b6d22e93f0133a000005 | What are the treatments of choice for GIST (gastrointestinal stromal tumor)? | The surgical resection is a treatment of choice for gastrointestinal stromal tumors. It has been shown that adequate surgical resection correlates with high 5-years survival rates for patients with gastric GIST. When they are localized, the treatment of choice is surgical excision, but advanced tumors have a limited response to chemo or radiotherapy. Imatinib (STI571 or Glivec) is a selective inhibitor or tyrosine kinase proteins that has been used successfully in the treatment of advanced GIST. | [
"16857109",
"19097381",
"18958964",
"15508453",
"16739060",
"15655606",
"12394270",
"16566359",
"15672765",
"22678007",
"15221987",
"17229322",
"16136600",
"15245670",
"17954092",
"11126742",
"18082353",
"16437936",
"17470686",
"14753595",
"19829995",
"19343179",
"16821517",
"17643218",
"18180842",
"15993051",
"24325620"
] | summary | [
{
"offsetInBeginSection": 178,
"offsetInEndSection": 258,
"text": "Traditionally, the treatment of choice for primary disease is surgical resection",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325620",
"endSection": "abstract"
},
{
"offsetInBeginSection": 269,
"offsetInEndSection": 524,
"text": "no single surgeon or institution gets extensive exposure to these patients so appropriate decision-making is difficult, particularly since the introduction of the tyrosine kinase inhibitor imatinib, which has become an important additional management tool",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325620",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1618,
"offsetInEndSection": 1686,
"text": "Surgery aiming at an R0 resection remains the mainstay of treatment.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325620",
"endSection": "abstract"
},
{
"offsetInBeginSection": 116,
"offsetInEndSection": 170,
"text": "The treatment of choice for GIST is surgical resection",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22678007",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1284,
"offsetInEndSection": 1422,
"text": "Extra luminal colonic gastrointestinal stromal tumors are very rare and can present as mass abdomen. Resection is the treatment of choice.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19829995",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 99,
"text": "Surgery remains the only curative treatment for gastrointestinal stromal tumour (GIST).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19343179",
"endSection": "abstract"
},
{
"offsetInBeginSection": 87,
"offsetInEndSection": 375,
"text": "When they are localized, the treatment of choice is surgical excision, but advanced tumors have a limited response to chemo or radiotherapy. Imatinib (STI571 or Glivec) is a selective inhibitor or tyrosine kinase proteins that has been used successfully in the treatment of advanced GIST.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18180842",
"endSection": "abstract"
},
{
"offsetInBeginSection": 632,
"offsetInEndSection": 717,
"text": "Therefore Imatinib can be a therapeutic alternative in patients with metastatic GIST.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18180842",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1550,
"offsetInEndSection": 1761,
"text": "The surgical resection is a treatment of choice for gastrointestinal stromal tumors. It has been shown that adequate surgical resection correlates with high 5-years survival rates for patients with gastric GIST.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19097381",
"endSection": "abstract"
},
{
"offsetInBeginSection": 442,
"offsetInEndSection": 737,
"text": "Approximately 80% of patients with metastatic GIST benefit from imatinib, although acquired resistance to the agent may develop. For patients with primary GIST, surgery remains the treatment of choice, and whether outcome is improved by adjuvant imatinib is currently under broad investigation. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16136600",
"endSection": "abstract"
},
{
"offsetInBeginSection": 739,
"offsetInEndSection": 873,
"text": "combination of imatinib therapy and surgery also may be effective in a subset of patients with metastatic or unresectable primary GIST",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16136600",
"endSection": "abstract"
}
] |
56be0e4aef6e394741000008 | List Kartagener Syndrome Triad. | The triad of situs inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. | [
"25207108",
"8080604",
"6984375",
"17725169",
"16940490",
"24019633",
"24730627",
"20550487",
"15025618",
"22966723",
"17408950",
"8290523",
"313731",
"19529061",
"14551758",
"9927835",
"9018261"
] | list | [
{
"offsetInBeginSection": 414,
"offsetInEndSection": 505,
"text": "The triad of situs inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24730627",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 173,
"text": "BACKGROUND: KARTAGENER SYNDROME (KS) IS A RARE CONGENITAL DISEASE CHARACTERISED BY A CLINICAL TRIAD OF SYMPTOMS: situs inversus, chronic rhinosinusitis, and bronchiectasis. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25207108",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 139,
"text": "Kartagener's syndrome is a very rare congenital malformation comprising of a classic triad of sinusitis, situs inversus and bronchiectasis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24019633",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 213,
"text": "We present a case of a patient with clinically definite ALS, who had earlier suffered from Kartagener syndrome, which is characterized by the triad comprising chronic sinusitis, bronchiectasis, and situs inversus.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20550487",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 148,
"text": "Kartagener syndrome (KS), an autosomal recessively inherited disease, is characterized by the triad of situs inversus, bronchiectasis and sinusitis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16940490",
"endSection": "abstract"
},
{
"offsetInBeginSection": 315,
"offsetInEndSection": 459,
"text": "In 1933, Manes Kartagener, a Zurich pulmonary physician, reported four patients with the triad of sinusitis, bronchiectasis, and situs inversus.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14551758",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 171,
"text": "A case of a nine year and eight months old child with Kartagener's syndrome (triad) is described: chronic maxillary sinusitis, bronchiectasis and \"situs inversus totalis\".",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/313731",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 178,
"text": "Kartagener's syndrome is an inherited disease characterized by a triad of symptoms--bronchiectasis, situs inversus and sinusitis--and is classified as an immotile cilia syndrome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9927835",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 106,
"text": "Kartagener's syndrome is characterized by the clinical triad of bronchitis, sinusitis, and situs inversus.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9018261",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 130,
"text": "Kartagener's syndrome is a well known classical triad of presentations consisting of bronchiectasis, sinusitis and situs inversus.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8080604",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 150,
"text": "Kartagener's syndrome is a rare disorder characterized by the triad of situs inversus, including dextrocardia, bronchiectasis and paranasal sinusitis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15025618",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 170,
"text": "Kartagener's syndrome is an inherited disease characterized by a triad of symptoms: bronchiectasis, situs inversus and sinusitis resulting from defective cilial motility.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17408950",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 201,
"text": "Ear, nose and throat symptoms and signs were studied in 15 patients with Kartagener's syndrome: a triad consisting of chronic rhinosinusitis, chronic bronchitis with bronchiectasis, and situs inversus.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/6984375",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 207,
"text": "Kartagener syndrome (a clinical variant of primary ciliary dyskinesia) is a recessive autossomical disease characterized by the triad of chronic sinusitis, bronchiectasis and situs inversus with dextrocardia",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17725169",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "Kartagener Syndrome is a rare autosomal recessive disorder consisting of triad of sinusitis, bronchiectasis and situs inversus with dextrocardia",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19529061",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 147,
"text": "Kartagener syndrome (KS), an autosomal recessively inherited disease, is characterized by the triad of situs inversus, bronchiectasis and sinusitis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16940490",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 182,
"text": "Kartagener's syndrome is an inherited disease characterized by a triad of symptoms--bronchiectasis, situs inversus and sinusitis--and is classified as an immotile cilia syndrome",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9927835",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 143,
"text": "Kartagener's syndrome is a very rare congenital malformation comprising of a classic triad of sinusitis, situs inversus and bronchiectasis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24019633",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 222,
"text": "A comprehensive clinicomorphological examination of 24 children with Zivert-Kartagener syndrome ascertained the complete triad (bronchiectasis, maldevelopment of the sinuses and transposition of the viscera) in all of them",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8290523",
"endSection": "abstract"
},
{
"offsetInBeginSection": 363,
"offsetInEndSection": 458,
"text": "The triad situs viscerum inversus, bronchiectasis and sinusitis is known as Kartagener syndrome",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22966723",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 324,
"text": "We present a case of a patient with clinically definite ALS, who had earlier suffered from Kartagener syndrome, which is characterized by the triad comprising chronic sinusitis, bronchiectasis, and situs inversus. Recent linkage and mutational analyses identified several genes that are responsible for Kartagener syndrome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20550487",
"endSection": "abstract"
}
] |
550f0e4c6a8cde6b72000003 | Which disease is associated with the ectopic expression of the protein encoded by the gene DUX4? | Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat. | [
"24232919",
"21529284",
"21484336",
"21951698",
"23777630",
"22718021",
"23966205",
"24075187",
"22536400",
"21288772",
"23593020",
"22798623",
"17984056",
"22892954",
"24030947",
"23108159",
"23644600",
"19829708",
"23143600"
] | factoid | [
{
"offsetInBeginSection": 571,
"offsetInEndSection": 667,
"text": "e expression of DUX4 has been confirmed in both FSHD cells and biopsies by several laboratories.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23966205",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1341,
"offsetInEndSection": 1516,
"text": "These results indicate that molecular markers of the disease are already expressed during fetal life, thus opening a new field of investigation for mechanisms leading to FSHD.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23966205",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 258,
"text": "Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020",
"endSection": "abstract"
},
{
"offsetInBeginSection": 702,
"offsetInEndSection": 992,
"text": "DUX4, the primary candidate for FSHD pathogenesis, is upregulated over ten-fold in FSHD myoblasts and myotubes with short telomeres, and its expression is inversely proportional to telomere length. FSHD may be the first known human disease in which TPE contributes to age-related phenotype.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23644600",
"endSection": "abstract"
},
{
"offsetInBeginSection": 128,
"offsetInEndSection": 319,
"text": "Upregulation of the DUX4 retrogene from the last D4Z4 repeated unit is thought to underlie FSHD pathophysiology. However, no one knows what triggers muscle defect and when alteration arises. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23777630",
"endSection": "abstract"
},
{
"offsetInBeginSection": 999,
"offsetInEndSection": 1161,
"text": "Recent studies have provided a plausible disease mechanism for FSHD in which FSHD results from inappropriate expression of the germline transcription factor DUX4.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22892954",
"endSection": "abstract"
},
{
"offsetInBeginSection": 214,
"offsetInEndSection": 485,
"text": "Recent studies have proposed that FSHD pathology is caused by the misexpression of the DUX4 (double homeobox 4) gene resulting in production of a pathogenic protein, DUX4-FL, which has been detected in FSHD, but not in unaffected control myogenic cells and muscle tissue.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22798623",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 153,
"text": "DUX4, a homeobox-containing gene present in a tandem array, is implicated in facioscapulohumeral muscular dystrophy (FSHD), a dominant autosomal disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22718021",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 180,
"text": "Facioscapulohumeral Disease (FSHD) is a dominantly inherited progressive myopathy associated with aberrant production of the transcription factor, Double Homeobox Protein 4 (DUX4).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22536400",
"endSection": "abstract"
},
{
"offsetInBeginSection": 250,
"offsetInEndSection": 379,
"text": " A DUX4 transcript derived from the last repeat unit in a contracted array is associated with pathogenesis but it is unclear how.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21951698",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2021,
"offsetInEndSection": 2304,
"text": "DUX4's pathogenic effect in FSHD may occur transiently at or before the stage of myoblast formation to establish a cascade of gene dysregulation. This contrasts with the current emphasis on toxic effects of experimentally upregulated DUX4 expression at the myoblast or myotube stages",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21951698",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 198,
"text": "Double homeobox 4 (DUX4) is a candidate disease gene for facioscapulohumeral dystrophy (FSHD), one of the most common muscular dystrophies characterized by progressive skeletal muscle degeneration. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21529284",
"endSection": "abstract"
},
{
"offsetInBeginSection": 399,
"offsetInEndSection": 648,
"text": "In FSHD, the combination of inefficient chromatin silencing of the D4Z4 repeat and polymorphisms on the FSHD-permissive alleles that stabilize the DUX4 mRNAs emanating from the repeat result in inappropriate DUX4 protein expression in muscle cells. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772",
"endSection": "abstract"
},
{
"offsetInBeginSection": 269,
"offsetInEndSection": 464,
"text": "In facioscapulohumeral muscular dystrophy, recent findings implicate a stabilized DUX4 transcript within the contracted D4Z4 repeats, opening the door for an RNA interference treatment strategy. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21484336",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1218,
"offsetInEndSection": 1327,
"text": " Aberrant expression of DUX4 from the last unit of the D4Z4 array has been proposed to be the cause of FSHD. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24232919",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 154,
"text": "Paired-like homeodomain transcription factor 1 (PITX1) was proposed to be part of the disease mechanisms of facioscapulohumeral muscular dystrophy (FSHD).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24232919",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 318,
"text": "Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array on chromosome 4 to a size of 1-10 units. The residual number of D4Z4 units inversely correlates with clinical severity, but significant clinical variability exists. Each unit contains a copy of the DUX4 retrogene. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24075187",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 184,
"text": "Facioscapulohumeral muscular dystrophy has been genetically linked to reduced numbers (≤ 8) of D4Z4 repeats at 4q35 combined with 4A(159/161/168) DUX4 polyadenylation signal haplotype.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24030947",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "Facioscapulohumeral muscular dystrophy (FSHD) is one of the most prevalent adult muscular dystrophies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23966205",
"endSection": "abstract"
},
{
"offsetInBeginSection": 518,
"offsetInEndSection": 667,
"text": "We mainly focus on DUX4 isoform expression because the expression of DUX4 has been confirmed in both FSHD cells and biopsies by several laboratories.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23966205",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 240,
"text": "Facio-scapulo-humeral dystrophy (FSHD) results from deletions in the subtelomeric macrosatellite D4Z4 array on the 4q35 region. Upregulation of the DUX4 retrogene from the last D4Z4 repeated unit is thought to underlie FSHD pathophysiology.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23777630",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 713,
"text": "Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy characterized by an asymmetric progressive weakness and wasting of the facial, shoulder and upper arm muscles, frequently accompanied by hearing loss and retinal vasculopathy. FSHD is an autosomal dominant disease linked to chromosome 4q35, but the causative gene remains controversial. DUX4 is a leading candidate gene as causative of FSHD. However, DUX4 expression is extremely low in FSHD muscle, and there is no DUX4 animal model that mirrors the pathology in human FSHD. Here, we show that the misexpression of very low levels of human DUX4 in zebrafish development recapitulates the phenotypes seen in human FSHD patients.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23108159",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1337,
"offsetInEndSection": 1595,
"text": "Our results suggest that the misexpression of DUX4-fl, even at extremely low level, can recapitulate the phenotype observed in FSHD patients in a vertebrate model. These results strongly support the current hypothesis for a role of DUX4 in FSHD pathogenesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23108159",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 154,
"text": "DUX4, a homeobox-containing gene present in a tandem array, is implicated in facioscapulohumeral muscular dystrophy (FSHD), a dominant autosomal disease. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22718021",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 320,
"text": "Facioscapulohumeral Disease (FSHD) is a dominantly inherited progressive myopathy associated with aberrant production of the transcription factor, Double Homeobox Protein 4 (DUX4). The expression of DUX4 depends on an open chromatin conformation of the D4Z4 macrosatellite array and a specific haplotype on chromosome 4.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22536400",
"endSection": "abstract"
},
{
"offsetInBeginSection": 321,
"offsetInEndSection": 491,
"text": "Even when these requirements are met, DUX4 transcripts and protein are only detectable in a subset of cells indicating that additional constraints govern DUX4 production.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22536400",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 398,
"text": "Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) has an unusual pathogenic mechanism. FSHD is caused by deletion of a subset of D4Z4 macrosatellite repeat units in the subtelomere of chromosome 4q. Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 390,
"text": "Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease linked to contractions of the D4Z4 repeat array in 4q35. We have previously identified a double homeobox gene (DUX4) within each D4Z4 unit that encodes a transcription factor expressed in FSHD but not control myoblasts. DUX4 and its target genes contribute to the global dysregulation of gene expression observed in FSHD. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19829708",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 172,
"text": "Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder linked to contractions of the D4Z4 repeat array in the subtelomeric region of chromosome 4q.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17984056",
"endSection": "abstract"
},
{
"offsetInBeginSection": 422,
"offsetInEndSection": 591,
"text": "In addition, we showed that the double homeobox 4 gene (DUX4) that maps within the D4Z4 repeat unit was up-regulated in patient myoblasts at both mRNA and protein level.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17984056",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1011,
"offsetInEndSection": 1156,
"text": "Our results suggest that up-regulation of both DUX4 and PITX1 in FSHD muscles may play critical roles in the molecular mechanisms of the disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17984056",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 191,
"text": "Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded DUX4 gene in skeletal muscle.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23143600",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 256,
"text": "Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020",
"endSection": "abstract"
}
] |
5319ac36b166e2b806000031 | Which G protein is essential in the formation and function of lamellipodia? | Recruitment of the small G-protein Rac1 to the plasma membrane is essential in inducing the local formation of specialized cellular processes termed lamellipodia. | [
"11709084",
"19801976",
"24265417",
"9301423",
"11230698"
] | factoid | [
{
"offsetInBeginSection": 1039,
"offsetInEndSection": 1329,
"text": "We specifically identified that the Spa homology domain (aa 250-420) of GIT1 is required for GIT1-cortactin complex localization to the leading edge. The mechanisms involved extracellular signal-regulated kinases 1 and 2-mediated Cortactin-S405 phosphorylation and activation of Rac1/Cdc42.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24265417",
"endSection": "abstract"
},
{
"offsetInBeginSection": 377,
"offsetInEndSection": 586,
"text": "We demonstrated the utility of this system with LAD constructs that can recruit the small G-protein Rac1 to the plasma membrane and induce the local formation of lamellipodia in response to focal illumination.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19801976",
"endSection": "abstract"
},
{
"offsetInBeginSection": 858,
"offsetInEndSection": 1122,
"text": "We found that fibroblasts from EDG-1 null embryos did not migrate toward PDGF or SPP, and inhibition of motility correlated with defective activation of the small guanosine triphosphatase Rac, which is required for lamellipodia formation and directional locomotion",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11709084",
"endSection": "abstract"
},
{
"offsetInBeginSection": 288,
"offsetInEndSection": 510,
"text": "Deletion of edg-1 or inhibition of sphingosine kinase suppressed chemotaxis toward PDGF and also activation of the small guanosine triphosphatase Rac, which is essential for protrusion of lamellipodia and forward movement.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11230698",
"endSection": "abstract"
},
{
"offsetInBeginSection": 530,
"offsetInEndSection": 714,
"text": "Evidence from these models indicates that migration is a highly complex process, which is likely to involve the tightly controlled spatial and temporal interaction of multiple factors:",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9301423",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1335,
"offsetInEndSection": 1479,
"text": "(v) molecules which regulate cytoskeletal function (e.g. Rac), which allows the formation of specialized cellular processes termed lamellipodia.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9301423",
"endSection": "abstract"
}
] |
54dfc6501388e8454a000009 | Which are the main functions of the APOBEC3 family of proteins? | The APOBEC3 family of cytidine deaminases play a critical role in host-mediated defense against exogenous viruses, most notably, human immunodeficiency virus type-1 (HIV-1), and endogenous transposable elements, such as LINE-1 and Alu retrotransposons. | [
"22915799",
"15466872",
"17439959",
"21966267",
"22720156",
"22203821",
"15994766",
"16557012"
] | list | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 199,
"text": "The APOBEC3 cytidine deaminases play a critical role in host-mediated defense against exogenous viruses, most notably, human immunodeficiency virus type-1 (HIV-1) and endogenous transposable elements",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22915799",
"endSection": "abstract"
},
{
"offsetInBeginSection": 6,
"offsetInEndSection": 82,
"text": "the identification of APOBEC3G (A3G) as a potent restriction factor of HIV-1",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22720156",
"endSection": "abstract"
},
{
"offsetInBeginSection": 472,
"offsetInEndSection": 631,
"text": "additional A3 family members have been identified as antiviral proteins, mechanistic details of the restrictive capacity of these proteins have been elucidated",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22720156",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 183,
"text": "Human APOBEC3 (A3) proteins are cellular cytidine deaminases that potently restrict the replication of retroviruses by hypermutating viral cDNA and/or inhibiting reverse transcription",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22203821",
"endSection": "abstract"
},
{
"offsetInBeginSection": 316,
"offsetInEndSection": 367,
"text": "A3F and A3G are the most potent inhibitors of HIV-1",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22203821",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 88,
"text": "APOBEC3A is a specific inhibitor of the early phases of HIV-1 infection in myeloid cells",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21966267",
"endSection": "title"
},
{
"offsetInBeginSection": 626,
"offsetInEndSection": 727,
"text": "we demonstrate that the pool of APOBEC3A in target cells inhibits the early phases of HIV-1 infection",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21966267",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1154,
"offsetInEndSection": 1374,
"text": "Our results indicate that APOBEC3A is a previously unrecognized antiviral factor that targets primate lentiviruses specifically in myeloid cells and that acts during the early phases of infection directly in target cells",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21966267",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 117,
"text": "Foamy virus Bet proteins function as novel inhibitors of the APOBEC3 family of innate antiretroviral defense factors.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15994766",
"endSection": "title"
},
{
"offsetInBeginSection": 518,
"offsetInEndSection": 727,
"text": "This inhibition correlated with the packaging of inhibitory APOBEC3 proteins into PFV virions, due to a specific PFV Gag/APOBEC3 interaction, and resulted in the G to A hypermutation of PFV reverse transcripts",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15994766",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 47,
"text": "[Antiviral defense by APOBEC3 family proteins].",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16557012",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 77,
"text": "All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17439959",
"endSection": "title"
},
{
"offsetInBeginSection": 1190,
"offsetInEndSection": 1314,
"text": "These findings raise the possibility that the different APOBEC3 family members function to neutralize specific lentiviruses.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15466872",
"endSection": "abstract"
}
] |
52e0c9a298d0239505000010 | Which histone modifications are associated with constitutive heterochromatin? | Strong methylation at H3 lysine 9 occurred preferentially in heterochromatic chromocenters of Arabidopsis nuclei. In general, heterochromatin has been linked to trimethylation of H3 at lysine 9 and parsimony analysis reveal that histone H3K9 methylation is, next to histone deacetylation, the evolutionary most stable heterochromatic mark. Classical histone modifications associated with heterochromatin also include H3K27me1 and H3K27me2. H3K36me3 function is not restricted to actively transcribed regions only and may contribute to the composition of heterochromatin. Other histone methylation marks usually found in constitutive heterochromatin are H4K20me3, H3K9me3, and H3K79me3. H3S10P is a good marker of pericentromeric heterochromatin. | [
"20562223",
"17710556",
"11850619",
"11356363",
"16705169",
"22572731",
"20599948",
"18004385",
"14506132",
"18987983",
"15368356",
"19786836",
"21267468",
"12581305",
"21803857"
] | list | [
{
"offsetInBeginSection": 163,
"offsetInEndSection": 432,
"text": "Remarkably, in mammalian somatic cells, H3S10P initiates in the pericentromeric heterochromatin during the late G2 phase, and phosphorylation spreads throughout the chromosomes arms in prophase, being maintained until the onset of anaphase when it gets dephosphorylated",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22572731",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1432,
"offsetInEndSection": 1744,
"text": "Based on these findings, we believe that H3S10P is a good marker of pericentromeric heterochromatin, especially in the late 1- and 2-cell stages as it labels both parental genomes and that it can be used to further investigate epigenetic regulation and heterochromatin mechanisms in early preimplantation embryos",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22572731",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 120,
"text": "3S10 phosphorylation marks constitutive heterochromatin during interphase in early mouse embryos until the 4-cell stage",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22572731",
"endSection": "title"
},
{
"offsetInBeginSection": 8,
"offsetInEndSection": 102,
"text": "H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857",
"endSection": "title"
},
{
"offsetInBeginSection": 393,
"offsetInEndSection": 664,
"text": "We show here that the maternally inherited Snurf-Snrpn 3-Mb region, which is silenced by a potent transcription repressive mechanism, is uniformly enriched in histone methylation marks usually found in constitutive heterochromatin, such as H4K20me3, H3K9me3, and H3K79me3",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857",
"endSection": "abstract"
},
{
"offsetInBeginSection": 899,
"offsetInEndSection": 1117,
"text": "We show that H3K36me3 deposition within this large heterochromatin domain does not correlate with transcription events, suggesting the existence of an alternative pathway for the deposition of this histone modification",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1119,
"offsetInEndSection": 1275,
"text": "In addition, we demonstrate that H3K36me3 is markedly enriched at the level of pericentromeric heterochromatin in mouse embryonic stem cells and fibroblasts",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1277,
"offsetInEndSection": 1381,
"text": "This result indicates that H3K36me3 is associated with both facultative and constitutive heterochromatin",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1383,
"offsetInEndSection": 1584,
"text": "Our data suggest that H3K36me3 function is not restricted to actively transcribed regions only and may contribute to the composition of heterochromatin, in combination with other histone modifications.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857",
"endSection": "abstract"
},
{
"offsetInBeginSection": 21,
"offsetInEndSection": 174,
"text": "accumulation of histone H3.3 and euchromatic histone modifications in pericentromeric heterochromatin in response to a decrease in DNA methylation levels",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20599948",
"endSection": "title"
},
{
"offsetInBeginSection": 247,
"offsetInEndSection": 440,
"text": "In this study, we show that inhibition of DNA methylation in mouse fibroblast cells affects histone modification and the subnuclear localization of histone H3.3 in a cell cycle-dependent manner",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20599948",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1169,
"offsetInEndSection": 1325,
"text": "Moreover, we found that histone H3.3 was deposited on the pericentromeric heterochromatin prior to the accumulation of the euchromatic histone modifications",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20599948",
"endSection": "abstract"
},
{
"offsetInBeginSection": 464,
"offsetInEndSection": 623,
"text": "Classical histone modifications associated with heterochromatin, including H3K9me2, H3K27me1 and H3K27me2, were distributed throughout both A and B chromosomes",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18987983",
"endSection": "abstract"
},
{
"offsetInBeginSection": 625,
"offsetInEndSection": 790,
"text": "However, H3K27me2 showed a reduced level on the B chromosome compared with the A chromosomes and was not associated with some classes of constitutive heterochromatin",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18987983",
"endSection": "abstract"
},
{
"offsetInBeginSection": 150,
"offsetInEndSection": 388,
"text": "Recently analyzed H3K9 methyltransferases (HMTases) as SUV39H1, Clr4p, DIM-5, Su(var)3-9 or SUVH2 are responsible for the establishment of histone H3 lysine 9 methylation (H3K9me), which is intimately connected with heterochromatinization",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17710556",
"endSection": "abstract"
},
{
"offsetInBeginSection": 23,
"offsetInEndSection": 92,
"text": "heterochromatic histone H3K9 methyltransferases left its marks behind",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17710556",
"endSection": "title"
},
{
"offsetInBeginSection": 815,
"offsetInEndSection": 1092,
"text": "Compilation and parsimony analysis reveal that histone H3K9 methylation is, next to histone deacetylation, the evolutionary most stable heterochromatic mark, which is established by at least two subfamilies of specialized heterochromatic HMTases in almost all studied eukaryote",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17710556",
"endSection": "abstract"
},
{
"offsetInBeginSection": 280,
"offsetInEndSection": 445,
"text": "Trimethylated H3(K9) marks pericentromeric constitutive heterochromatin and the male Y chromosome, while H2A.Z is dramatically reduced at these chromosomal locations",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16705169",
"endSection": "abstract"
},
{
"offsetInBeginSection": 448,
"offsetInEndSection": 754,
"text": "Of eight tested antibodies, the one for histone H4 acetylated at lysine 4, 8, 12, or 16 was best for distinguishing constitutive heterochromatin from unexpressed euchromatin, but differences in the extent of immunoprecipitation of these two types of chromatin were only modest, although highly reproducible",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15368356",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1255,
"offsetInEndSection": 1465,
"text": "In addition, immunocytochemical analysis was done with an antibody to heterochromatin protein 1alpha (HP1alpha), whose preferential binding to heterochromatin has been linked to trimethylation of H3 at lysine 9",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15368356",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1467,
"offsetInEndSection": 1756,
"text": "Our combined ChIP and immunocytochemical results suggest that factors other than hypoacetylation of the N-terminal tails of H4 and hypermethylation of H3 at lysine 9 can play an important role in determining whether a chromatin sequence in mammalian cells is constitutively heterochromatic",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15368356",
"endSection": "abstract"
},
{
"offsetInBeginSection": 599,
"offsetInEndSection": 819,
"text": "To test for the putative heterochromatinization, we quantitated chromatin immunoprecipitation with an antibody for acetylated histone H4 that discriminates between constitutive heterochromatin and unexpressed euchromatin",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14506132",
"endSection": "abstract"
},
{
"offsetInBeginSection": 38,
"offsetInEndSection": 117,
"text": "high methylation of H3 lysine 9 is dispensable for constitutive heterochromatin",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12581305",
"endSection": "title"
},
{
"offsetInBeginSection": 546,
"offsetInEndSection": 729,
"text": "Strong methylation at H3 lysine 4 was restricted to euchromatin, while strong methylation at H3 lysine 9 occurred preferentially in heterochromatic chromocenters of Arabidopsis nuclei",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12581305",
"endSection": "abstract"
}
] |
530cf54dab4de4de0c00000c | What is the main application of SWATH-MS in proteomics? | Using the method called SWATH-MS one might ask sample sets for the presence and quantity of essentially any protein of interest. | [
"23227840",
"23322582",
"22261725",
"23811049"
] | factoid | [
{
"offsetInBeginSection": 829,
"offsetInEndSection": 992,
"text": "it is a valuable resource for the selection of candidate proteotypic peptides for targeted proteomic experiments via Selected Reaction Monitoring (SRM) or SWATH-MS",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23811049",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 272,
"text": "SWATH-MS is a data-independent acquisition method that generates, in a single measurement, a complete recording of the fragment ion spectra of all the analytes in a biological sample for which the precursor ions are within a predetermined m/z versus retention time window.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23322582",
"endSection": "abstract"
},
{
"offsetInBeginSection": 836,
"offsetInEndSection": 1007,
"text": "ew strategies, such as SWATH™ MS, which allows us to systematically characterize and quantify query sample sets of 'any protein of interest' in complex biological samples,",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23227840",
"endSection": "abstract"
},
{
"offsetInBeginSection": 375,
"offsetInEndSection": 516,
"text": "Here we present a new strategy that systematically queries sample sets for the presence and quantity of essentially any protein of interest. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22261725",
"endSection": "abstract"
}
] |
515ed87c298dcd4e51000032 | Do selenoproteins and selenium play a role in prostate cancer prevention? | No, although initial epidemiological studies on humans and on animal and cell- based models indicated that selenoproteins may be protecting against prostate cancer, more research is needed to improve the understanding of selenium metabolism and requirements for optimal health. | [
"19074884",
"23133653",
"19299660",
"19690186",
"20852007",
"20424130",
"22072582",
"15875088",
"16690748",
"17160069"
] | yesno | [
{
"offsetInBeginSection": 1115,
"offsetInEndSection": 1402,
"text": "The selenoprotein-deficient mice exhibited accelerated development of lesions associated with prostate cancer progression, implicating selenoproteins in cancer risk and development and raising the possibility that selenium prevents cancer by modulating the levels of these selenoproteins",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16690748",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1293,
"offsetInEndSection": 1564,
"text": "Notably and in contrast to previous studies, RWPE-1 cells were significantly more sensitive to selenite than either of the prostate cancer cell lines. These results demonstrate that selenoproteins and selenium metabolism are regulated at multiple levels in prostate cells",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17160069",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1783,
"offsetInEndSection": 2110,
"text": "In a low-selenium population, SOD2-Ala16+ men homozygous for SEPP1-Ala234 are at an increased risk of prostate cancer/aggressive prostate cancer especially if ever-smokers, because they are likely to produce more mitochondrial H(2)O(2) that they cannot remove, thereby promoting prostate tumor cell proliferation and migration.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19074884",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1417,
"offsetInEndSection": 1566,
"text": "Our results support a role of selenium and polymorphisms in selenoenzymes in prostate cancer etiology, which warrants confirmation in future studies.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20852007",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1470,
"offsetInEndSection": 1767,
"text": "This study provides evidence that SEP15 genetic variation may influence PCa mortality. Additionally, the association of selenium with PCa mortality was modified by a variant, suggesting the possibility that some men with PCa may benefit more from selenium than others, depending on their genotype.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20424130",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1619,
"offsetInEndSection": 1752,
"text": "We conclude that decreased SEPP concentration in serum might represent an additional valuable marker for prostate cancer diagnostics.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19690186",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 289,
"text": "The recently completed Selenium and Vitamin E Cancer Prevention Trial (SELECT) was one of the largest human cancer prevention trials ever undertaken. Its purpose was to assess the role of selenium and vitamin E in prostate cancer prevention, but SELECT found no decline in prostate cancer.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19299660",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 325,
"offsetInEndSection": 928,
"text": "We studied Se levels in whole blood, plasma and prostate of 32 PC and 40 benign prostate hyperplasia (BPH) patients and in the control group composed of 39 healthy subjects. The selenoenzyme glutathione peroxidase (GSH-Px) was also measured in the patients' red cells, plasma and prostate tissue. Se concentration in whole blood and plasma in both groups of patients was lower as compared with controls, while in prostate gland it was significantly higher in PC than in BPH patients and controls. Red cell GSH-Px activity was the same in PC patients and controls but significantly lower in BPH patients.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15875088",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1352,
"offsetInEndSection": 1553,
"text": "Of particular interest was the positive correlation between tissue GPx activity and Gleason score, with this relationship achieving statistical significance among African-Americans (r = 0.67, P = 0.02)",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22072582",
"endSection": "sections.0"
}
] |
52bf217003868f1b0600001b | What can Nothobranchius furzeri be used as a model system for? | N. furzeri an interesting model system to investigate the effects of experimental manipulations on longevity and age-related pathologies.
N. furzeri could represent a model system for studying the genetic control of life-history traits in natural populations.
N. furzeri could be a very useful model for comparative genomics of aging.
It can be employed to test the effects of experimental manipulation on aging and apharmacological research. | [
"19302373",
"19052641",
"17049789",
"16687936",
"16164422"
] | factoid | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 270,
"text": "The short-lived annual fish Nothobranchius furzeri shows extremely short captive life span and accelerated expression of age markers, making it an interesting model system to investigate the effects of experimental manipulations on longevity and age-related pathologies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19302373",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1339,
"offsetInEndSection": 1527,
"text": "Owing to large differences in aging phenotypes in different lines, N. furzeri could represent a model system for studying the genetic control of life-history traits in natural populations.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19052641",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1201,
"offsetInEndSection": 1362,
"text": "It is very close to the Japanese Medaka, and close to the pufferfishes and stickleback and might represent a very useful model for comparative genomics of aging.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17049789",
"endSection": "abstract"
},
{
"offsetInBeginSection": 991,
"offsetInEndSection": 1111,
"text": "In the last three years, N. furzeri has moved from biological curiosity to a promising model system for drug validation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17049789",
"endSection": "abstract"
},
{
"offsetInBeginSection": 645,
"offsetInEndSection": 1244,
"text": " This result identifies resveratrol as the first molecule which consistently retards aging in organisms as diverse as yeast, worm, fly and fish, but it also reveals the potential of this short-lived fish as an animal model for pharmacological research. Moreover, being related to stickleback (Gasterosteus aculeatus) the \"pufferfishes\" Takifugu and Tetraodon, and even more closely related to medaka (Oryzias latipes), it can greatly beneficiate from the recent development of genomic resources for these fish models and in the future become a complete model system for the aging research community.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16687936",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1340,
"offsetInEndSection": 1610,
"text": "These fishes can become excellent models for aging studies. They can be employed to test the effects of experimental manipulation on aging at a pace comparable with that of Drosophila and to probe the effects of natural selection on the evolution of aging-related genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16164422",
"endSection": "abstract"
}
] |
515dc691298dcd4e5100001b | What is the function of TALENs? | These chimeric enzymes can be used to introduce a double strand break at a specific genomic site which then can become the substrate for error-prone non-homologous end joining (NHEJ), generating mutations at the site of cleavage. Artificial transcription activator-like effector nucleases (TALENs) provide a powerful new approach for targeted zebrafish genome editing and functional genomic applications. Transcription Activator-Like Effector Nucleases (TALENs) consist of a nuclease domain fused to a DNA binding domain which is engineered to bind to any genomic sequence. Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs. | [
"22624882",
"23027955",
"23000899",
"23555929"
] | summary | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 156,
"text": "Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23027955",
"endSection": "sections.0"
}
] |
54d796f93706e8952800001e | Has protein citrullination been implicated in rheumatoid arthritis? | Yes, protein citrullination been implicated in rheumatoid arthritis. | [
"24823363",
"25182207",
"25475141",
"24763532",
"24724574",
"25116951",
"24498912",
"25520183",
"25515746",
"24782594",
"25355199",
"24497204"
] | yesno | [
{
"offsetInBeginSection": 30,
"offsetInEndSection": 193,
"text": ": Citrullination has become a hot topic within recent years due to its involvement in diseases such as rheumatoid arthritis (RA), multiple sclerosis and fibrosis. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25520183",
"endSection": "abstract"
},
{
"offsetInBeginSection": 802,
"offsetInEndSection": 933,
"text": "Current literature suggests that increased levels of citrullinated proteins are found in several if not all inflammatory diseases. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25520183",
"endSection": "abstract"
},
{
"offsetInBeginSection": 234,
"offsetInEndSection": 377,
"text": "Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing RA. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25515746",
"endSection": "abstract"
},
{
"offsetInBeginSection": 152,
"offsetInEndSection": 306,
"text": "Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation in general. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25475141",
"endSection": "abstract"
},
{
"offsetInBeginSection": 982,
"offsetInEndSection": 1180,
"text": "Some ACPA are remarkably effective as diagnostics in autoimmune disorders, most notably rheumatoid arthritis (RA). Several ACPA can be observed before other clinical RA manifestations are apparent. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25355199",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 177,
"text": "Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein/peptide autoantibodies (ACPAs). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25182207",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 91,
"text": "Anti-citrullinated peptides as autoantigens in rheumatoid arthritis-relevance to treatment.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25182207",
"endSection": "title"
},
{
"offsetInBeginSection": 1248,
"offsetInEndSection": 1467,
"text": "The implications of citrullination affecting integrin binding in disease open up a new area of study and might have implications for the pathogenesis of inflammatory diseases like rheumatoid arthritis and periodontitis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25116951",
"endSection": "abstract"
},
{
"offsetInBeginSection": 636,
"offsetInEndSection": 777,
"text": "In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24782594",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 90,
"text": "Citrullinated collagen II (CII) is a well-known autoantigen in rheumatoid arthritis (RA). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24823363",
"endSection": "abstract"
},
{
"offsetInBeginSection": 355,
"offsetInEndSection": 501,
"text": "Among the RA-associated autoantibodies, especially anti-citrullinated protein antibodies (ACPAs) have been studied intensively in the last decade.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24763532",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 159,
"text": "Protein citrullination is a posttranslational modification that has attracted increased attention, especially for its involvement in rheumatoid arthritis (RA).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24724574",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 111,
"text": "Identification of citrullinated cellular fibronectin in synovial fluid from patients with rheumatoid arthritis.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24498912",
"endSection": "title"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 206,
"text": "Cellular fibronectin (cFn) has been implicated in the pathogenesis of rheumatoid arthritis (RA), and we previously demonstrated the presence of citrullinated cFn in rheumatoid synovial tissues. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24498912",
"endSection": "abstract"
},
{
"offsetInBeginSection": 122,
"offsetInEndSection": 313,
"text": ". In rheumatoid arthritis, PAD4 and protein citrullination are increased in inflamed joints, and anti-citrullinated protein antibodies (ACPAs) form against citrullinated antigens are formed. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24497204",
"endSection": "abstract"
}
] |
535d613f7d100faa09000002 | Show results of randomised controlled trials for certolizumab pegol. | Improvement of clinical results (ACR50, 28 joint disease activity score (DAS-28) remission and HAQ scores) with certolizumab pegol. Adverse events were more frequent with certolizumab; there was a statistically significant increase in the number of serious adverse events, infections and hypertension.
Randomised controlled trials (RCTs) of CZP have demonstrated rapid improvements in workplace and home productivity. | [
"24092417",
"21328299",
"22165979",
"21047485"
] | summary | [
{
"offsetInBeginSection": 654,
"offsetInEndSection": 1387,
"text": "RESULTS: 4049 RA patients who received CZP were included in the safety pooling; total exposure 9277 PY, mean exposure 2.1 years (range 0.04-7.6). SIE, most frequently pneumonia (IR 0.73/100 PY), were the most common serious AE, occurring more frequently in CZP compared to placebo-treated patients in RCT (IR 5.61/100 PY vs 1.35/100 PY, odds ratio (OR) 4.35, 95% CI 0.65 to 29.30). SIE rates were lower in the CZP-treated population including OLE (ER 4.33/100 PY). 44 patients developed tuberculosis (IR 0.47/100 PY), 39 from high endemic regions. 58 deaths occurred in CZP-exposed patients (IR 0.63/100 PY) and 70 developed malignancies excluding non-melanoma skin cancer (IR 0.76/100 PY), including five lymphomas (IR 0.05/100 PY).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24092417",
"endSection": "abstract"
},
{
"offsetInBeginSection": 864,
"offsetInEndSection": 1277,
"text": "As well as displaying clinical efficacy, there is evidence to suggest that CZP has unique characteristics, including reduced transfer across the placenta and reduced frequency of injection site reactions. Furthermore, randomised controlled trials (RCTs) of CZP have demonstrated rapid improvements in workplace and home productivity in patients contributing to reducing the significant socioeconomic burden of RA.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22165979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 272,
"offsetInEndSection": 452,
"text": "To assess the effectiveness and safety of certolizumab pegol (CDP870) in patients with RA who have not responded well to conventional disease modifying anti-rheumatic drugs (DMARDs",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21328299",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2633,
"offsetInEndSection": 2998,
"text": " With an overall high grade of evidence this review revealed an improvement of clinical results (ACR50, 28 joint disease activity score (DAS-28) remission and HAQ scores) with certolizumab pegol. Adverse events were more frequent with certolizumab; there was a statistically significant increase in the number of serious adverse events, infections and hypertension.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21328299",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1404,
"offsetInEndSection": 2772,
"text": "The clinical evidence was derived from two multicentre blinded randomised controlled trials (RCTs) comparing CZP + MTX to placebo + MTX (the RAPID 1 and RAPID 2 trials). RAPID 1 lasted 52 weeks with 982 patients and RAPID 2 24 weeks with 619 patients. Evidence for clinical effectiveness of CZP in mono-therapy came from the 24-week FAST4WARD trial with 220 patients that compared CZP (400 mg every 4 weeks) versus placebo. The three key RCTs demonstrated statistically significant superiority of CZP + MTX versus placebo + MTX and of CZP versus placebo with respect to a variety of outcomes including ACR 20, ACR 50 and ACR 70 measures and quality of life measures at 3 and 6 months. On the basis of results from the indirect comparison meta-analyses, the manufacturer suggested that CZP may be at least as effective as other 'biological' DMARD (bDMARD) comparators and, in a few ACR measures at 3 and 6 months, more effective. CZP is an effective therapy for adult RA patients whose disease has failed to respond adequately to cDMARDs including MTX or who are intolerant of MTX. The cost-effectiveness of CZP relative to other bDMARDs is unclear because the economic modelling undertaken may have ignored relevant effectiveness data and potential differences between trial populations, and so may have included effectiveness results that were biased in favour of CZP",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21047485",
"endSection": "abstract"
}
] |
54f2228e64850a5854000002 | Which is the mass-tag that reveal the ubiquitination of a lysine residue? | Lys-ɛ-Gly-Gly (K-ɛ-GG) is the remnant produced by trypsin digestion of proteins having ubiquitinated lysine side chains. | [
"24196352",
"24051958",
"24142993",
"24167568",
"24251111",
"23682733",
"23707720"
] | factoid | [
{
"offsetInBeginSection": 191,
"offsetInEndSection": 449,
"text": "antibodies that recognize the Lys-ɛ-Gly-Gly (K-ɛ-GG) remnant produced by trypsin digestion of proteins having ubiquitinated lysine side chains have markedly improved the ability to enrich and detect endogenous ubiquitination sites by mass spectrometry (MS). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24051958",
"endSection": "abstract"
},
{
"offsetInBeginSection": 602,
"offsetInEndSection": 798,
"text": "Recent publications have also highlighted the use of peptide-level immunoaffinity enrichment of K-GG modified peptides from whole cell lysates for global characterization of ubiquitination sites. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24142993",
"endSection": "abstract"
},
{
"offsetInBeginSection": 508,
"offsetInEndSection": 726,
"text": "In this work, levels of lysine ubiquitination were quantitated using a structurally homologous label that is chemically similar to the diglycine (GlyGly) tag, which is left at the ubiquitination site upon trypsinolysis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23682733",
"endSection": "abstract"
},
{
"offsetInBeginSection": 507,
"offsetInEndSection": 687,
"text": "Tandem mass spectrometry (LC-MS/MS) analysis of immunoprecipitated proteins resulted in the identification of five peptides containing ubiquitin (diglycine) modifications on eIF2Bε",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23707720",
"endSection": "abstract"
}
] |
5323640b9b2d7acc7e000014 | Which gene is involved in CADASIL? | Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of familial vascular dementia, is caused by mutations of the NOTCH3 gene. | [
"19788051",
"22664156",
"17854869",
"21038489",
"19539236",
"19018300",
"20224942",
"17726918",
"18313300",
"21702048",
"17622327",
"17996090",
"19255248",
"22878905",
"23308019"
] | factoid | [
{
"offsetInBeginSection": 71,
"offsetInEndSection": 195,
"text": "leukoencephalopathy (CADASIL), the most common form of familial vascular dementia, is caused by mutations of the NOTCH3 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22664156",
"endSection": "abstract"
},
{
"offsetInBeginSection": 301,
"offsetInEndSection": 594,
"text": "Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by mutations of the Notch3 gene encoding the Notch3 protein. Notch3 is involved in the regulation of apoptosis, modulating Fas-Ligand (Fas-L)- induced apoptosis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22878905",
"endSection": "abstract"
},
{
"offsetInBeginSection": 9,
"offsetInEndSection": 189,
"text": ": Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small vessel disease of the brain caused by mutations in the NOTCH3 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23308019",
"endSection": "abstract"
},
{
"offsetInBeginSection": 263,
"offsetInEndSection": 467,
"text": "Mutations in Notch3 gene are linked to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a disorder characterized by stroke and dementia in young adults",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21702048",
"endSection": "abstract"
},
{
"offsetInBeginSection": 91,
"offsetInEndSection": 252,
"text": "(CADASIL) is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke, cognitive decline, psychiatric disturbances and migraine",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21038489",
"endSection": "abstract"
},
{
"offsetInBeginSection": 11,
"offsetInEndSection": 298,
"text": "To evaluate the role of apoptosis in the pathogenesis of brain lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary microangiopathy leading to cognitive decline and dementia, caused by mutations in the NOTCH3 gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19788051",
"endSection": "abstract"
},
{
"offsetInBeginSection": 467,
"offsetInEndSection": 616,
"text": "NOTCH3 (Notch homolog 3), the gene involved in CADASIL, encodes a transmembrane receptor primarily expressed in systemic arterial smooth-muscle cells",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19539236",
"endSection": "abstract"
},
{
"offsetInBeginSection": 91,
"offsetInEndSection": 352,
"text": "(CADASIL) is a vascular dementing disease caused by mutations in the NOTCH3 gene, most which are missense mutations leading to an uneven number of cysteine residues in epidermal growth factor-like repeats in the extracellular domain of Notch3 receptor (N3ECD). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17622327",
"endSection": "abstract"
}
] |
516beae9298dcd4e5100006b | What is the role of thyroid hormone receptor alpha1 in insulin secretion? | Liganded TR(alpha) plays a critical role in beta-cell replication and in expansion of the beta-cell mass. the TRalpha P398H mutation which cannot bind T3, is associated with insulin resistance. Loss of Thra protects mice from high-fat diet-induced hepatic and peripheral insulin resistance. | [
"22147010",
"12869545",
"20529852"
] | summary | [
{
"offsetInBeginSection": 1290,
"offsetInEndSection": 1408,
"text": "loss of Thra protects mice from high-fat diet-induced hepatic steatosis and hepatic and peripheral insulin resistance.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22147010",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1481,
"offsetInEndSection": 1745,
"text": "liganded TR(alpha) plays a critical role in beta-cell replication and in expansion of the beta-cell mass during postnatal development. Thus, liganded TR(alpha) may be a target for therapeutic strategies that can induce the expansion and regeneration of beta-cells.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20529852",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1240,
"offsetInEndSection": 1327,
"text": "the TRalpha P398H mutation is associated with visceral adiposity and insulin resistance",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12869545",
"endSection": "sections.0"
}
] |
56e2985951531f7e33000013 | Do R-loops tend to form at sites of DNA replication? | R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins. Physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. One mechanism may be that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. This would allow replication to proceed while the original block is repaired or bypassed. Thus, the organized structure of the R-loop is critical for primer RNA function in vivo with important implications for the RNA processing and DNA replication machinery. | [
"15569610",
"7774596",
"10082645",
"21191184",
"9119223",
"25569209",
"21979917",
"9009281",
"22195969",
"20495385",
"21129203",
"22965135",
"9150892",
"25487262",
"25972891",
"19841062",
"22464441",
"8798672"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 184,
"text": "Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7774596",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1161,
"offsetInEndSection": 1340,
"text": "We propose that the organized structure of the R-loop is critical for primer RNA function in vivo with important implications for the RNA processing and DNA replication machinery.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8798672",
"endSection": "abstract"
},
{
"offsetInBeginSection": 143,
"offsetInEndSection": 344,
"text": "The precursor primer RNA exists as a persistent RNA-DNA hybrid, known as an R-loop, formed during transcription through the replication origin (Xu, B., and Clayton, D. A. (1996) EMBO J. 15, 3135-3143).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8798672",
"endSection": "abstract"
},
{
"offsetInBeginSection": 113,
"offsetInEndSection": 344,
"text": "We found that overproduction of RecG protein drastically decreased copy numbers of ColE1-type plasmids, which require R-loop formation between the template DNA and a primer RNA transcript (RNA II) for the initiation of replication.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9009281",
"endSection": "abstract"
},
{
"offsetInBeginSection": 580,
"offsetInEndSection": 986,
"text": "These results suggest that overproduced RecG inhibits the initiation of replication by prematurely resolving the R-loops formed at the replication origin region of these plasmids with its unique helicase activity. The possibility that RecG regulates the initiation of a unique mode of DNA replication, oriC-independent constitutive stable DNA replication, by its activity in resolving R-loops is discussed.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9009281",
"endSection": "abstract"
},
{
"offsetInBeginSection": 602,
"offsetInEndSection": 864,
"text": "We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. This would allow replication to proceed while the original block is repaired or bypassed",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15569610",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1028,
"offsetInEndSection": 1263,
"text": "Furthermore, increased RNaseH expression significantly alleviated genomic instability in deficient fibroblasts suggesting that cotranscriptional R-loops formation contributes to the genesis of replication-dependent DSBs in these cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21191184",
"endSection": "abstract"
},
{
"offsetInBeginSection": 144,
"offsetInEndSection": 442,
"text": "Transcription is an important source of replicative stress and consequently, maintenance of genome integrity requires the protection of chromosomes from the deleterious effects arising from the interaction between nascent RNAs and template DNA, leading to stable DNA-RNA hybrids (R-loop) formation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21191184",
"endSection": "abstract"
},
{
"offsetInBeginSection": 621,
"offsetInEndSection": 760,
"text": "Strikingly, we found that attenuation of replication strongly suppresses R-loop-mediated DNA rearrangements in both E. coli and HeLa cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21979917",
"endSection": "abstract"
},
{
"offsetInBeginSection": 453,
"offsetInEndSection": 618,
"text": "More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stabilit",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21979917",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 91,
"text": "R-loop-mediated genomic instability is caused by impairment of replication fork progression",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21979917",
"endSection": "title"
},
{
"offsetInBeginSection": 724,
"offsetInEndSection": 922,
"text": "When any of these processes are not properly coordinated, aberrant outcomes such as fork reversal and R-loop formation arise and trigger unscheduled recombinogenic events and genome rearrangements. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22464441",
"endSection": "abstract"
},
{
"offsetInBeginSection": 952,
"offsetInEndSection": 1208,
"text": "Many studies show that cells can manage R loop formation with efficiency, and can also process the R-loops already formed in the cell, and by which, the bad effects of R-loops on DNA replication, gene mutation and homologous recombination can be regulated.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25487262",
"endSection": "abstract"
},
{
"offsetInBeginSection": 245,
"offsetInEndSection": 462,
"text": "Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891",
"endSection": "abstract"
},
{
"offsetInBeginSection": 662,
"offsetInEndSection": 904,
"text": "In agreement with this, we found that R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins, precisely at the position displaying the highest density of G4 motifs. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891",
"endSection": "abstract"
},
{
"offsetInBeginSection": 932,
"offsetInEndSection": 1187,
"text": "connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891",
"endSection": "abstract"
},
{
"offsetInBeginSection": 620,
"offsetInEndSection": 769,
"text": "We show that RNA:DNA hybrids (R-loops) form at sites of transcription/replication collisions and that RNase H1 functions to suppress CFS instability.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22195969",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 73,
"text": "R-loops and initiation of DNA replication in human cells: a missing link?",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 95,
"text": "Stable RNA-DNA hybrids (R-loops) prime the initiation of replication in Escherichia coli cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10082645",
"endSection": "abstract"
},
{
"offsetInBeginSection": 770,
"offsetInEndSection": 943,
"text": "We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15569610",
"endSection": "abstract"
},
{
"offsetInBeginSection": 284,
"offsetInEndSection": 473,
"text": "Immediately after infection, RNA-DNA hybrids (R-loops) occur on (at least some) replication origins, with the annealed RNA serving as a primer for leading-strand synthesis in one direction.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21129203",
"endSection": "abstract"
},
{
"offsetInBeginSection": 460,
"offsetInEndSection": 676,
"text": "Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891",
"endSection": "abstract"
},
{
"offsetInBeginSection": 445,
"offsetInEndSection": 572,
"text": "ColE1 plasmid origins of replication and oriK sites initiate primosome assembly by an RNA-DNA hybrid structure known as R-loop.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15569610",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1183,
"offsetInEndSection": 1466,
"text": "This scenario builds on the connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891",
"endSection": "abstract"
},
{
"offsetInBeginSection": 673,
"offsetInEndSection": 880,
"text": "The multiple cleavage sites on the R-loop substrate match the priming sites observed in vivo, suggesting that RNase MRP alone is capable of generating virtually all of the leading-strand replication primers.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9119223",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 99,
"text": "Mechanisms of primer RNA synthesis and D-loop/R-loop-dependent DNA replication in Escherichia coli.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9150892",
"endSection": "title"
},
{
"offsetInBeginSection": 582,
"offsetInEndSection": 773,
"text": "Alternative oriC-independent modes of replication initiation are possible, one of which is constitutive stable DNA replication (cSDR) from transcription-associated RNA-DNA hybrids or R-loops.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25569209",
"endSection": "abstract"
},
{
"offsetInBeginSection": 401,
"offsetInEndSection": 601,
"text": "Our results suggest that Top1 execute this function by suppressing the formation of DNA-RNA hybrids during transcription, these so-called R-loops interfering with the progression of replication forks.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20495385",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 58,
"text": "Critical role of R-loops in processing replication blocks.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15569610",
"endSection": "title"
},
{
"offsetInBeginSection": 794,
"offsetInEndSection": 986,
"text": "The possibility that RecG regulates the initiation of a unique mode of DNA replication, oriC-independent constitutive stable DNA replication, by its activity in resolving R-loops is discussed.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9009281",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 156,
"text": "Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19841062",
"endSection": "title"
},
{
"offsetInBeginSection": 453,
"offsetInEndSection": 621,
"text": "More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21979917",
"endSection": "abstract"
},
{
"offsetInBeginSection": 331,
"offsetInEndSection": 517,
"text": "Consistent with this hypothesis, the 3' ends of the mitochondrial R-loop formed by in vitro transcription are located close to the initiation sites of the mitochondrial DNA replication. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10082645",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 124,
"text": "A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22965135",
"endSection": "title"
},
{
"offsetInBeginSection": 414,
"offsetInEndSection": 583,
"text": "Previous studies have shown that the newly synthesized primers form a stable and persistent RNA-DNA hybrid, a R-loop, near the leading-strand origin of DNA replication. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22965135",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 185,
"text": "Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7774596",
"endSection": "abstract"
}
] |
51487ef9d24251bc05000031 | Which two catechol-O-methyl transferase (COMT) inhibitors can be used for treatment of Parkinson disease? | Tolcapone (central and peripheral) and entacapone (peripheral) are catechol-O-methyl transferase inhibitors that are used for treatment of Parkinson disease. | [
"14741081",
"15853578",
"11147512",
"11147511",
"15372589",
"21164341",
"19589043",
"10733264",
"12588639",
"8784230",
"1933685",
"12952501",
"10651109",
"19198095"
] | list | [
{
"offsetInBeginSection": 11,
"offsetInEndSection": 215,
"text": "Entacapone is a highly potent, reversible, peripherally acting catechol-O-methyl transferase (COMT) inhibitor that is used as an adjunct to L-dopa in the treatment of patients with Parkinson disease (PD).",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21164341",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1251,
"offsetInEndSection": 1614,
"text": "Stalevo is a combination tablet comprised of levodopa, carbidopa, and the COMT inhibitor entacapone. It is available in fixed-dose combinations of levodopa/carbidopa/entacapone, 50/12.5/200, 75/18.75/200, 100/25/200, 125/31.25/200, 150/37.5/200 and 200/50/200 mg. Stalevo is currently approved for use in Parkinson's disease patients with end-of-dose wearing off.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19589043",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 306,
"offsetInEndSection": 637,
"text": "Good news were marketing of ropinirole, a new non-ergot agonist, in December 2006 and entacapone, the first catechol-O-methyl transferase (COMT) inhibitor in Japan in April 2007. Having faced these new situations, Japanese Neurological Association has started revising \"the Guideline 2002 for the treatment of Parkinson's disease\".",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19198095",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 620,
"offsetInEndSection": 776,
"text": "Stalevo (Orion) combines levodopa, the dopa-decarboxylase inhibitor carbidopa and the catechol-O-methyl transferase inhibitor entacapone in a single tablet.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15853578",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 250,
"text": "We investigated whether administration of the catechol-O-methyl transferase (COMT) inhibitor entacapone, at doses of 200 mg and 400 mg, alters the pharmacokinetics of apomorphine in Parkinson's disease patients experiencing severe motor fluctuations.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15372589",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 197,
"text": "The catechol-O-methyl transferase inhibitor entacapone is given in combination with levodopa/dopa decarboxylase inhibitor for Parkinson's disease (PD) patients experiencing end-of-dose wearing-off.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14741081",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 325,
"text": "Entacapone (Comtess/Comtan) is Orion Pharma's original proprietary catechol-O-methyl transferase (COMT) inhibitor. Entacapone is able to slow down degradation of levodopa and improve the availability and efficacy of each levodopa dose, hence its use as a complement to levodopa/carbidopa in patients with Parkinson's disease.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12952501",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 77,
"text": "Sleep attacks in Parkinson's disease induced by Entacapone, a COMT-inhibitor.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12588639",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 266,
"text": "We present a patient who suffered from sleep attacks after starting entacapone in addition to levodopa. Entacapone, a catechol-O-methyl transferase inhibitor, alters the pharmacokinetics of levodopa, leading to increase of levodopa concentration in plasma and brain.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12588639",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 160,
"offsetInEndSection": 273,
"text": "Two COMT inhibitors, tolcapone and entacapone, have recently been made available as adjunctive agents to levodopa",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11147512",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 185,
"text": "Two inhibitors of catechol-O-methyl transferase (COMT), tolcapone and entacapone, have recently been introduced as adjuncts to levodopa in the treatment of Parkinson's disease patients.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11147511",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1446,
"offsetInEndSection": 1569,
"text": "Tolcapone, a peripheral and central COMT inhibitor, appears to be quite effective, producing a 47% reduction in 'off' time.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10733264",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1761,
"offsetInEndSection": 1957,
"text": ". Entacapone, a purely peripheral COMT inhibitor with a lower potency than tolcapone, has also proved to be effective and has not been associated with liver damage, obviating the need for testing.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10733264",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 316,
"offsetInEndSection": 524,
"text": "Here we report that a treatment of the cerebral tissue with tolcapone, a central and peripheral inhibitor of COMT, does not change the membrane responses of midbrain dopamine neurons to dopamine and levodopa.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10651109",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 721,
"offsetInEndSection": 873,
"text": "Therefore, the therapeutic action of tolcapone in Parkinson's disease, might be dependent on the reduction of COMT activity in the extracerebral tissue.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10651109",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 294,
"offsetInEndSection": 568,
"text": "Pretreatment with entacapone (OR-611), a peripheral catechol O-methyl-transferase (COMT) inhibitor, greatly reduces the plasma 3OMFD fraction and provides an ideal situation to evaluate the contribution of the plasma 3OMFD fraction in several kinetic models of FDOPA uptake.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8784230",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 87,
"offsetInEndSection": 356,
"text": "The novel and reversible inhibitors are the catechol-O-methyl-transferase (COMT) inhibitors, Ro 40-7592 (3,4-dihydroxy-4'-methyl-5-nitrobenzophenone), and the monoamine oxidase type-B (MAO-B) inhibitor, Ro 19-6327 (N-(2-aminoethyl)-5-chloro-2-pyridine carboxamide HC1).",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1933685",
"endSection": "sections.0"
}
] |
5505db6a8e1671127b000003 | What are the structures formed when keratin molecules come together? | Keratins form the intermediate filaments of the cytoskeleton and provide scaffold structures within cells. | [
"22502568",
"21721843",
"22585043",
"23396250",
"22963508",
"22168818",
"21945137",
"23331681",
"21844209",
"22507538",
"22238362",
"22250786"
] | factoid | [
{
"offsetInBeginSection": 512,
"offsetInEndSection": 619,
"text": " Keratins form the intermediate filaments of the cytoskeleton and provide scaffold structures within cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23396250",
"endSection": "abstract"
},
{
"offsetInBeginSection": 29,
"offsetInEndSection": 59,
"text": "keratin intermediate filaments",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23396250",
"endSection": "title"
},
{
"offsetInBeginSection": 612,
"offsetInEndSection": 642,
"text": "keratin intermediate filaments",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23331681",
"endSection": "abstract"
},
{
"offsetInBeginSection": 56,
"offsetInEndSection": 94,
"text": "keratin intermediate filament protein.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22963508",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 57,
"text": "Keratin is a protein in the intermediate filament family ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22963508",
"endSection": "abstract"
},
{
"offsetInBeginSection": 519,
"offsetInEndSection": 571,
"text": "Keratins are the intermediate filament (IF) proteins",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22585043",
"endSection": "abstract"
},
{
"offsetInBeginSection": 577,
"offsetInEndSection": 658,
"text": "squamous keratinocytes contain polymerized keratin intermediate filament bundles ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22507538",
"endSection": "abstract"
},
{
"offsetInBeginSection": 451,
"offsetInEndSection": 470,
"text": " keratin filaments ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22502568",
"endSection": "abstract"
},
{
"offsetInBeginSection": 385,
"offsetInEndSection": 506,
"text": " In this study, we have examined the distribution of four groups of IFs [cytokeratins (CKs), vimentin, desmin and lamins]",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22250786",
"endSection": "abstract"
},
{
"offsetInBeginSection": 547,
"offsetInEndSection": 571,
"text": "keratin filament network",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22238362",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 180,
"text": "An intact keratin 5/keratin 14 intermediate filament cytoskeleton is vital for the integrity of basal keratinocytes and for the development and maintenance of epidermal structures.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22168818",
"endSection": "abstract"
},
{
"offsetInBeginSection": 860,
"offsetInEndSection": 903,
"text": "keratin intermediate filament cytoskeleton.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21945137",
"endSection": "abstract"
},
{
"offsetInBeginSection": 846,
"offsetInEndSection": 864,
"text": "keratin filaments,",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21844209",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1119,
"offsetInEndSection": 1148,
"text": "keratin filamentous network. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21721843",
"endSection": "abstract"
}
] |
531d1998267d7dd053000001 | Which is the prognostic impact of hypothyroidism in patients with acute myocardial infarction? | Thyroid dysfunction, particularly low T3 syndrome, is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions. | [
"16330914",
"19609889",
"23124142",
"11747849",
"23990180"
] | factoid | [
{
"offsetInBeginSection": 1073,
"offsetInEndSection": 1258,
"text": "In-hospital cardiogenic shock (15% vs 3% in the control group; p<0.01) and death (7% vs 1% in the control group; p<0.01) were more frequently observed in the thyroid dysfunction group. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23990180",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1443,
"offsetInEndSection": 1633,
"text": "Thyroid dysfunction, particularly sick euthyroid syndrome, was found to be related to in-hospital and long term mortality in patients with STEMI undergoing primary percutaneous intervention.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23990180",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1387,
"offsetInEndSection": 1582,
"text": "A low fT3 level, a common phenomenon in patients with acute myocardial infarctions, is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23124142",
"endSection": "abstract"
},
{
"offsetInBeginSection": 828,
"offsetInEndSection": 1149,
"text": "Troponin T and creatine kinase-B with an M-type subunit levels were significantly higher in the nonsurvivors when compared with survivors. Survivors in the AMI group had higher TT3, TT4, and lower FT4 levels, while the nonsurvivors in the AMI group had higher thyrotrophin and lower TT3, FT3 and FT4 levels than controls.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16330914",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1215,
"offsetInEndSection": 1530,
"text": "Reverse T3 levels >0.41 nmol/L were associated with an increased risk of 1-year mortality (hazard ratio = 3.0; 95% confidence interval: 1.4 to 6.3; P = 0.005), independent of age, previous myocardial infarction, prior angina, heart failure, serum creatinine level, and peak serum creatine kinase-MB fraction levels.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11747849",
"endSection": "abstract"
}
] |
56c9f9d95795f9a73e00001e | Which are the main features of CREST and other ALS-linked proteins? | CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity. | [
"13129802",
"25173930",
"24360741",
"16808883",
"24115583",
"24355598",
"24920614",
"25888396"
] | summary | [
{
"offsetInBeginSection": 115,
"offsetInEndSection": 248,
"text": "Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 534,
"offsetInEndSection": 624,
"text": "Like several other ALS-associated proteins, CREST is recruited to induced stress granules.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1257,
"offsetInEndSection": 1453,
"text": "CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 115,
"offsetInEndSection": 247,
"text": "Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 533,
"offsetInEndSection": 623,
"text": " Like several other ALS-associated proteins, CREST is recruited to induced stress granules",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1234,
"offsetInEndSection": 1453,
"text": "Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 103,
"offsetInEndSection": 235,
"text": "Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1204,
"offsetInEndSection": 1571,
"text": "Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity. A change in CREST levels in neurons which might occur under pathological conditions would have a profound negative effect on neuronal homeostasis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 165,
"text": "Calcium-responsive transactivator (CREST) protein shares a set of structural and functional traits with other proteins associated with amyotrophic lateral sclerosis.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396",
"endSection": "title"
},
{
"offsetInBeginSection": 25,
"offsetInEndSection": 114,
"text": "calcium-responsive transactivator (CREST) encoding gene have been recently linked to ALS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 127,
"offsetInEndSection": 373,
"text": "A de novo mutation in the SS18L1 (also known as CREST or KIAA0693) gene encoding the calcium-responsive transactivator and/or neuronal chromatin remodeling complex subunit has recently been identified by exome sequencing of 47 sporadic ALS trios.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24360741",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1201,
"offsetInEndSection": 1529,
"text": "Here we report that profilin 1 and related protein profilin 2 are novel stress granule-associated proteins in mouse primary cortical neurons and in human cell lines and that ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24920614",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 103,
"text": "Aggregation of ALS-linked FUS mutant sequesters RNA binding proteins and impairs RNA granules formation",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25173930",
"endSection": "title"
},
{
"offsetInBeginSection": 374,
"offsetInEndSection": 501,
"text": "In the present study, we examined the effects of ALS-linked FUS mutants on ALS-associated RNA binding proteins and RNA granules",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25173930",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 104,
"text": "Aggregation of ALS-linked FUS mutant sequesters RNA binding proteins and impairs RNA granules formation.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25173930",
"endSection": "title"
}
] |
54c225bcf693c3b16b000002 | Mutations of which genes have been associated with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)? | Mutations in five genes – ryanodine receptor 2 (RYR2), calsequestrin 2(CASQ2), triadic (TRDN), calmodulin 1 (CALM1) and potassium channel, inwardly rectifying subfamily J, member 2 (KCNJ2) – have been found to be associated with CPVT | [
"20301466",
"22422768",
"24370574",
"23595086",
"20807279",
"22787013",
"22589293",
"16601229",
"25480325",
"23908839"
] | list | [
{
"offsetInBeginSection": 1703,
"offsetInEndSection": 1921,
"text": "Mutation in four genes – RYR2, CASQ2, TRDN, and CALM1 – is known to cause CPVT or related phenotypes of adrenergically induced life-threatening arrhythmias. The presence of other as-yet unidentified loci is postulated ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20301466",
"endSection": "abstract"
},
{
"offsetInBeginSection": 239,
"offsetInEndSection": 384,
"text": "some KCNJ2 mutation carriers lack the ATS triad and sometimes share the phenotype of catecholaminergic polymorphic ventricular tachycardia (CPVT)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22589293",
"endSection": "abstract"
},
{
"offsetInBeginSection": 246,
"offsetInEndSection": 513,
"text": "In 50 Japanese probands from unrelated families who satisfied clinical criteria for CPVT, genetic testing was conducted in all exons on 3 CPVT-related genes: cardiac ryanodine receptor 2 (RYR2), calsequestrin 2 (CASQ2) and inward rectifier potassium channel 2 (KCNJ2)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23595086",
"endSection": "abstract"
},
{
"offsetInBeginSection": 621,
"offsetInEndSection": 947,
"text": "point mutations in RYR2, the gene encoding for the cardiac isoform of the RyR (RyR2), are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), an arrhythmogenic syndrome characterized by the development of adrenergically-mediated ventricular tachycardia in individuals with an apparently normal heart.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25480325",
"endSection": "abstract"
},
{
"offsetInBeginSection": 464,
"offsetInEndSection": 528,
"text": "Recessive CPVT variants are due to mutations in the CASQ2 gene. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24370574",
"endSection": "abstract"
},
{
"offsetInBeginSection": 367,
"offsetInEndSection": 507,
"text": "Recent studies have shown that CPVT is caused by mutations in the cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23908839",
"endSection": "abstract"
},
{
"offsetInBeginSection": 689,
"offsetInEndSection": 817,
"text": "We identified three mutations in triadin which cosegregated with the disease on a recessive mode of transmission in two families",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22422768",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 206,
"text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmogenic disorder associated with mutations in the cardiac ryanodine receptor (RyR2) and cardiac calsequestrin (CASQ2) genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16601229",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 209,
"text": "BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22787013",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 238,
"text": "BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20807279",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 212,
"text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease so far related to mutations in the cardiac ryanodine receptor (RYR2) or the cardiac calsequestrin (CASQ2) genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22422768",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 196,
"text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22787013",
"endSection": "abstract"
}
] |
5173a8b48ed59a060a00001d | What is the relationship between nucleosomes and exons? | Nucleosomes are preferentially located within exons compared to nearby intronic sequences. Preferential positioning within the exons is indepedent of gene expression levels, stronger in exons with weak splice sites and conserved through metazoan evolution. | [
"20808788",
"21859475",
"21289049",
"19687145",
"19684599",
"20097656",
"15862762",
"22683623",
"22954214",
"19823040",
"8918932",
"9461388",
"11724736"
] | summary | [
{
"offsetInBeginSection": 372,
"offsetInEndSection": 557,
"text": "Nucleosomes preferentially are located at the ends of exons, thus protecting splice junctions, with the N9 positions of guanines of the GT and AG junctions oriented toward the histones.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22954214",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 397,
"offsetInEndSection": 691,
"text": "Nucleosomes were found to be preferentially positioned within constitutive exons and/or constitutive portions of alternative exons, which was not associated with gene expression or states of cells but was based on sequence and positively related with the sequence conservation of splicing sites",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22683623",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 375,
"offsetInEndSection": 632,
"text": "Here, we discuss the evidence supporting these ideas, from the first proposal of chromatin affecting alternative splicing, performed 20 years ago, to the latest findings including genome-wide evidence that nucleosomes are preferentially positioned in exons.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21289049",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 545,
"offsetInEndSection": 814,
"text": "Here we show, by analysis of data sets from human sperm and T cells and medaka (Japanese killifish, Oryzias latipes) blastulae, that internal exons of genes are characterized by sharply elevated average nucleosome occupancy in comparison to flanking intronic sequences.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19823040",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 376,
"offsetInEndSection": 645,
"text": "sing public data, we here show that there is a higher nucleosome-positioning signal in internal human exons and that this positioning is independent of expression. We observed a similarly strong nucleosome-positioning signal in internal exons of Caenorhabditis elegans.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19687145",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 234,
"offsetInEndSection": 371,
"text": "we have found stable nucleosome occupancy within human and Caenorhabditis elegans exons that is stronger in exons with weak splice sites.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19684599",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 172,
"offsetInEndSection": 289,
"text": "This confirms previously reported findings about preferential positioning of splice junctions within the nucleosomes.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15862762",
"endSection": "sections.0"
}
] |
532c0d7fd6d3ac6a3400001c | List programs suitable for pharmacophore modelling | A pharmacophore is an abstract description of molecular features which are necessary for molecular recognition of a ligand by a biological macromolecule. The IUPAC defines a pharmacophore to be "an ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target and to trigger (or block) its biological response". A pharmacophore model explains how structurally diverse ligands can bind to a common receptor site. Furthermore pharmacophore models can be used to identify through denovo design or virtual screening novel ligands that will bind to the same receptor. Nowadays there are many programs suitable for pharmacophore modelling such as LigandScout, Discovery Studio, Catalyst, PharmaGist, Genetic Algorithm Similarity and Molecular Operating Environment. | [
"20499259",
"20045317",
"22272142",
"22779800",
"19691298",
"23140189",
"22553386",
"21955456",
"18763758",
"23202316",
"21342558",
"20085380",
"20055175",
"21179343",
"22435086",
"17477520",
"20116902",
"22587766",
"9651155",
"21143043",
"21284830",
"20427100",
"20621485",
"17668276",
"21138791",
"22546667"
] | list | [
{
"offsetInBeginSection": 138,
"offsetInEndSection": 260,
"text": "Pharmacophore models based on thermolysin binding modes and activity profiles were generated using the LigandScout program",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22587766",
"endSection": "abstract"
},
{
"offsetInBeginSection": 145,
"offsetInEndSection": 318,
"text": "In this study, pharmacophore hypotheses based on known inhibitors were generated using common feature pharmacophore generation protocol available in Discovery Studio program",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21143043",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1083,
"offsetInEndSection": 1163,
"text": " A pharmacophore-based screening was then carried out using the program Catalyst",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17668276",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1038,
"offsetInEndSection": 1633,
"text": "The PharmaGist employed algorithm to identify the best pharmacophores by computing multiple flexible alignments between the input ligands. The multiple alignments are generated by combining alignments pair-wise between one of the gliptin input ligands, which acts as pivot and the other gliptin as ligand. The resulting multiple alignments reveal spatial arrangements of consensus features shared by different subsets of input ligands. The best pharmacophore model has been derived using both pair-wise and multiple alignment methods, which have been weighted in Pharmacophore Generation process",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23140189",
"endSection": "abstract"
},
{
"offsetInBeginSection": 152,
"offsetInEndSection": 325,
"text": "Pharmacophore models of c-Met kinase inhibitors have been developed based on 22 diverse compounds by using HypoGen algorithm implemented in Discovery studio program package.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22779800",
"endSection": "abstract"
},
{
"offsetInBeginSection": 15,
"offsetInEndSection": 179,
"text": "chemical feature based pharmacophore models of MMP-1, MMP-8 and MMP-13 inhibitors have been developed with the aid of HypoGen module within Catalyst program package",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22553386",
"endSection": "abstract"
},
{
"offsetInBeginSection": 320,
"offsetInEndSection": 458,
"text": "Genetic Algorithm Similarity Program (GASP) was used to derive a 3D pharmacophore model which was used in effective alignment of data set.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22546667",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1085,
"offsetInEndSection": 1255,
"text": "Active site complimenting structure-based pharmacophore models were developed using Discovery Studio 2.5 program and validated using a dataset of known HDAC8 inhibitors. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22272142",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1314,
"offsetInEndSection": 1438,
"text": " pharmacophore model has been generated from the training set by means of the MOE (molecular operating environment) program.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21955456",
"endSection": "abstract"
},
{
"offsetInBeginSection": 982,
"offsetInEndSection": 1169,
"text": "A training set of 20 compounds with known experimental activity was used to generate pharmacophore hypotheses using 3D QSAR Pharmacophore Generation module available in Discovery studio. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21342558",
"endSection": "abstract"
},
{
"offsetInBeginSection": 529,
"offsetInEndSection": 664,
"text": "Pharmacophore model was developed for the first time, on a training data set of 22 CCR3 antagonists, using CATALYST HypoRefine program.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21284830",
"endSection": "abstract"
},
{
"offsetInBeginSection": 227,
"offsetInEndSection": 394,
"text": "The CatalystHipHop approach was used to generate a pharmacophore model for cyclooxygenase-2 (COX-2) inhibitors based on a training set of 15 active inhibitors (1â15). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21179343",
"endSection": "abstract"
},
{
"offsetInBeginSection": 127,
"offsetInEndSection": 305,
"text": " Molecular modeling study, including fitting to a 3D-pharmacophore model of the designed molecules (10a-g), with HCV NS3 protease hypothesis using catalyst program was fulfilled.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21138791",
"endSection": "abstract"
},
{
"offsetInBeginSection": 4,
"offsetInEndSection": 135,
"text": "pharmacophore model (Hypo1) with a well prediction capacity for CysLT(1) antagonists was developed using Catalyst/HypoGen program. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20621485",
"endSection": "abstract"
},
{
"offsetInBeginSection": 225,
"offsetInEndSection": 317,
"text": "Three pharmacophore models of opioid agonists were generated by the Catalyst/HypoGen program",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20499259",
"endSection": "abstract"
},
{
"offsetInBeginSection": 229,
"offsetInEndSection": 328,
"text": "The superposition of the ligands was performed with the tool Pharmacophore Elucidation (MOE-package",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20427100",
"endSection": "abstract"
},
{
"offsetInBeginSection": 591,
"offsetInEndSection": 738,
"text": "Known PDE-5 inhibitors were used to construct a three dimensional quantitative structure-activity relationship (3D QSAR) model by HypoGen program. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20085380",
"endSection": "abstract"
},
{
"offsetInBeginSection": 18,
"offsetInEndSection": 167,
"text": "pharmacophore models were generated for AT1 and ET(A) receptors based on highly selective AT1 and ET(A) antagonists using the program Catalyst/HipHop",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20055175",
"endSection": "abstract"
},
{
"offsetInBeginSection": 132,
"offsetInEndSection": 309,
"text": " In this study, chemical feature based pharmacophore models of inhibitors of 5-LOX have been developed with the aid of HipHop and HypoGen modules within Catalyst program package",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20045317",
"endSection": "abstract"
},
{
"offsetInBeginSection": 131,
"offsetInEndSection": 303,
"text": "A data set consisting of 24 inhibitors was selected on the basis of the information content of the structures and activity data as required by the Catalyst/HypoGen program.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19691298",
"endSection": "abstract"
}
] |
550c1ca3a103b78016000003 | Is selenium deficiency involved in autoimmune thyroid disease? | Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interactionIn areas with severe selenium deficiency higher incidence of thyroiditis has been reported due to a decreased activity of selenium-dependent glutathione peroxidase enzyme within thyroid cells | [
"15132715",
"22009156",
"20810577",
"21896670",
"23448365",
"19034261",
"11932302",
"17160166",
"23565426",
"23786024"
] | yesno | [
{
"offsetInBeginSection": 14,
"offsetInEndSection": 205,
"text": "In areas with severe selenium deficiency higher incidence of thyroiditis has been reported due to a decreased activity of selenium-dependent glutathione peroxidase enzyme within thyroid cells",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23565426",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1028,
"offsetInEndSection": 1355,
"text": "Of 30 patients in the selenium treated group, 6 patients were overtly hypothyroid, 15 were subclinical hypothyroid, 6 were euthyroid, and 3 were subclinical hyperthyroid. The mean TPOAb concentration decreased significantly by 49.5% (P < 0.013) in the selenium treated group versus 10.1% (P < 0.95) in the placebo-treated group",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23565426",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1369,
"offsetInEndSection": 1479,
"text": "Selenium substitution has a significant impact on inflammatory activity in thyroid-specific autoimmune disease",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23565426",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 56,
"text": "Serum selenium is low in newly diagnosed Graves' disease",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23448365",
"endSection": "title"
},
{
"offsetInBeginSection": 678,
"offsetInEndSection": 801,
"text": "S-Se was lower in patients with GD than in controls (mean (SD), GD: 89·9 μg/l (18·4); controls: 98·8 μg/l (19·7), P < 0·01)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23448365",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1371,
"offsetInEndSection": 1603,
"text": "Patients with newly diagnosed GD and AIH had significantly lower s-Se compared with random controls. Our observation supports the postulated link between inadequate selenium supply and overt autoimmune thyroid disease, especially GD",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23448365",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1618,
"offsetInEndSection": 1852,
"text": "Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22009156",
"endSection": "abstract"
},
{
"offsetInBeginSection": 9,
"offsetInEndSection": 437,
"text": "The recent recognition that the essential trace element selenium is incorporated as selenocysteine in all three deiodinases has decisively confirmed the clear-cut link between selenium and thyroid function. It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1669,
"offsetInEndSection": 1834,
"text": "Maintenance of \"selenostasis\" via optimal intake not only aids preservation of general health but also contributes substantially to the prevention of thyroid disease",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577",
"endSection": "abstract"
},
{
"offsetInBeginSection": 520,
"offsetInEndSection": 844,
"text": "Low birth weight, iodine excess and deficiency, selenium deficiency, parity, oral contraceptive use, reproductive span, fetal microchimerism, stress, seasonal variation, allergy, smoking, radiation damage to the thyroid gland, viral and bacterial infections all play a role in the development of autoimmune thyroid disorders",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15132715",
"endSection": "abstract"
},
{
"offsetInBeginSection": 205,
"offsetInEndSection": 428,
"text": "It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 111,
"text": "Selenium deficiency may play an important role in the initiation and progression of autoimmune thyroid disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23448365",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 77,
"text": "[Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases].",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19034261",
"endSection": "title"
},
{
"offsetInBeginSection": 516,
"offsetInEndSection": 842,
"text": "Low birth weight, iodine excess and deficiency, selenium deficiency, parity, oral contraceptive use, reproductive span, fetal microchimerism, stress, seasonal variation, allergy, smoking, radiation damage to the thyroid gland, viral and bacterial infections all play a role in the development of autoimmune thyroid disorders.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15132715",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1083,
"offsetInEndSection": 1304,
"text": "Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22009156",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1356,
"offsetInEndSection": 1489,
"text": "Our observation supports the postulated link between inadequate selenium supply and overt autoimmune thyroid disease, especially GD.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23448365",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 77,
"text": "Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases].",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19034261",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 184,
"text": "Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21896670",
"endSection": "abstract"
},
{
"offsetInBeginSection": 216,
"offsetInEndSection": 438,
"text": "It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577",
"endSection": "abstract"
},
{
"offsetInBeginSection": 920,
"offsetInEndSection": 1222,
"text": "EVIDENCE SYNTHESIS: Evidence in support of selenium supplementation in thyroid autoimmune disease is evaluated, the results herein presented demonstrating the potential effectiveness of selenium in reducing the antithyroid peroxidase titer and improving the echostructure in the ultrasound examination.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1139,
"offsetInEndSection": 1288,
"text": "Some investigators suggest that selenium may be a useful adjunctive treatment for autoimmune thyroid diseases, such as Hashimoto and Graves' disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17160166",
"endSection": "abstract"
},
{
"offsetInBeginSection": 273,
"offsetInEndSection": 395,
"text": "Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11932302",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1091,
"offsetInEndSection": 1311,
"text": "Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22009156",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1090,
"offsetInEndSection": 1309,
"text": "Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22009156",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 145,
"text": "High prevalence of hyperplastic and autoimmune diseases of thyroid in Ukrainian population is determined by endemic deficit of iodine and selenium",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23786024",
"endSection": "abstract"
},
{
"offsetInBeginSection": 207,
"offsetInEndSection": 429,
"text": "It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577",
"endSection": "abstract"
},
{
"offsetInBeginSection": 273,
"offsetInEndSection": 394,
"text": "Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11932302",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1139,
"offsetInEndSection": 1287,
"text": "Some investigators suggest that selenium may be a useful adjunctive treatment for autoimmune thyroid diseases, such as Hashimoto and Graves' disease",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17160166",
"endSection": "abstract"
}
] |
530c844e970c65fa6b000014 | List disorders that are caused by mutations in the mitochondrial MTND6 gene. | Mitochondrial MTND6 gene mutations are the cause of Leigh syndrome and Leber's hereditary optic neuropathy and/or dystonia. | [
"24126373",
"16885236",
"8090716",
"7654063",
"22970697",
"16044424",
"23847141"
] | list | [
{
"offsetInBeginSection": 1216,
"offsetInEndSection": 1364,
"text": "It was shown that m14487T>C can also cause the unusual combination of optic atrophy, ptosis, and encephalomyopathy leading to intractable seizures. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24126373",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1289,
"offsetInEndSection": 1426,
"text": " MTND6 genes were identified as 'hotspots' of mutations, with Leigh syndrome accounting for the large majority of associated phenotypes. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23847141",
"endSection": "abstract"
},
{
"offsetInBeginSection": 425,
"offsetInEndSection": 538,
"text": "he 14487T>C mutation in MTND6 were present in two probands with Leigh's-like and Leigh's syndrome, respectively. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16044424",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1085,
"offsetInEndSection": 1214,
"text": "These results confirm the association of the MTND6*LDYT14459A mutation with Leber's hereditary optic neuropathy and/or dystonia. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7654063",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 248,
"text": "A novel point mutation in the ND6 subunit of complex I at position 14,459 of the mitochondrial DNA (MTND6*LDY T14459A) was identified as a candidate mutation for the highly tissue-specific disease. Leber's hereditary optic neuropathy plus dystonia.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7654063",
"endSection": "abstract"
},
{
"offsetInBeginSection": 939,
"offsetInEndSection": 1139,
"text": "Representative of these mutations is a heteroplasmic mutation in MTND6 at np 14459 whose clinical presentations range from adult-onset blindness to pediatric dystonia and basal ganglial degeneration. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8090716",
"endSection": "abstract"
}
] |
571653aecb4ef8864c000005 | Which are the most common methods for ctDNA (circulating tumour DNA) detection? | Recently, nanoplasmonics has emerged as a platform for one-step dual detection with high sensitivity and specificity. The practice of "liquid biopsy" as a diagnostic, prognostic and theranostic tool in non-small cell lung cancer (NSCLC) patients is an appealing approach, at least in theory, since it is noninvasive and easily repeated. Cancer personalized profiling by deep sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. A new DNA sensor using a nickel(II) phenanthroline complex ([Ni(phen)(2)PHPIP]·2ClO(4)) as the electrochemical probe was developed. The sensor is very sensitive and selective for calf thymus DNA (ctDNA) detection in aqueous medium. | [
"25220802",
"26539452",
"24705333",
"25489581",
"20970979"
] | list | [
{
"offsetInBeginSection": 147,
"offsetInEndSection": 220,
"text": "existing methods for ctDNA detection are restricted to genetic mutations.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25220802",
"endSection": "abstract"
},
{
"offsetInBeginSection": 221,
"offsetInEndSection": 338,
"text": "Recently, nanoplasmonics has emerged as a platform for one-step dual detection with high sensitivity and specificity.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25220802",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1250,
"offsetInEndSection": 1498,
"text": "These results demonstrate that the sensor can simultaneously detect the hot-spot mutation and epigenetic changes on the ctDNA. Promisingly, other specific-tumor mutants and epigenetic changes can be detected at low concentration with this platform.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25220802",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 217,
"text": "The practice of \"liquid biopsy\" as a diagnostic, prognostic and theranostic tool in non-small cell lung cancer (NSCLC) patients is an appealing approach, at least in theory, since it is noninvasive and easily repeated",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25489581",
"endSection": "abstract"
},
{
"offsetInBeginSection": 221,
"offsetInEndSection": 363,
"text": "Here we introduce cancer personalized profiling by deep sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24705333",
"endSection": "abstract"
},
{
"offsetInBeginSection": 937,
"offsetInEndSection": 1171,
"text": "Finally, we evaluated biopsy-free tumor screening and genotyping with CAPP-Seq. We envision that CAPP-Seq could be routinely applied clinically to detect and monitor diverse malignancies, thus facilitating personalized cancer therapy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24705333",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 122,
"text": "Synthesis of a new Ni-phenanthroline complex and its application as an electrochemical probe for detection of nucleic acid",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20970979",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 232,
"text": "A new DNA sensor using a nickel(II) phenanthroline complex ([Ni(phen)(2)PHPIP]·2ClO(4)) as the electrochemical probe was developed. The sensor is very sensitive and selective for calf thymus DNA (ctDNA) detection in aqueous medium. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20970979",
"endSection": "abstract"
}
] |
52bf1d2e03868f1b0600000c | Which gene is associated with Muenke syndrome? | Muenke syndrome has been related to a mutation on the Fibroblast Growth Factor Receptor (FGFR3) gene. | [
"15241680",
"17036334",
"19449410",
"17103449",
"24168007",
"19215249",
"17414289",
"22622662",
"19755431",
"12794698",
"21403557",
"20592905",
"18000976",
"14963686",
"23044018",
"19086028",
"23378035"
] | factoid | [
{
"offsetInBeginSection": 12,
"offsetInEndSection": 140,
"text": "Abstract Muenke is a fibroblast growth factor receptor 3 (FGFR-3) associated syndrome, which was first described in late 1990s. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24168007",
"endSection": "abstract"
},
{
"offsetInBeginSection": 295,
"offsetInEndSection": 475,
"text": "The syndrome is defined molecularly by a unique point mutation c.749C>G in exon 7 of the FGFR3 gene which results to an amino acid substitution p.Pro250Arg of the protein product. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24168007",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 164,
"text": "Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23378035",
"endSection": "abstract"
},
{
"offsetInBeginSection": 410,
"offsetInEndSection": 528,
"text": "Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 197,
"text": "Muenke syndrome is characterized by various craniofacial deformities and is caused by an autosomal-dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3(P250R) ).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22622662",
"endSection": "abstract"
},
{
"offsetInBeginSection": 267,
"offsetInEndSection": 437,
"text": "The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21403557",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 251,
"text": "The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20592905",
"endSection": "abstract"
},
{
"offsetInBeginSection": 648,
"offsetInEndSection": 788,
"text": "Here, we report a familial case of MS in a female patient with a Pro250Arg mutation in exon 7 (IgII-IGIII linker domain) of the FGFR3 gene. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20592905",
"endSection": "abstract"
},
{
"offsetInBeginSection": 547,
"offsetInEndSection": 807,
"text": " Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19755431",
"endSection": "abstract"
},
{
"offsetInBeginSection": 243,
"offsetInEndSection": 407,
"text": "We report on a set of identical twins with a de novo C749G mutation in the FGFR3 gene codon 250 after a pregnancy complicated by prenatal exposure to Nortriptyline.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19449410",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 296,
"text": "Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19215249",
"endSection": "abstract"
},
{
"offsetInBeginSection": 418,
"offsetInEndSection": 542,
"text": "The identification of the P250R mutation allowed the confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19215249",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 247,
"text": "Muenke syndrome, defined by heterozygosity for a Pro250Arg substitution in fibroblast growth factor receptor 3 (FGFR3), is the most common genetic cause of craniosynostosis in humans. We have used gene targeting to introduce the Muenke syndrome mu",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19086028",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 224,
"text": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976",
"endSection": "abstract"
},
{
"offsetInBeginSection": 342,
"offsetInEndSection": 579,
"text": "To better define the clinical features of this syndrome, we initiated a study of the natural history of Muenke syndrome. To date, we have conducted a standardized evaluation of nine patients with a confirmed Pro250Arg mutation in FGFR3. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976",
"endSection": "abstract"
},
{
"offsetInBeginSection": 364,
"offsetInEndSection": 532,
"text": "The patients were either placed into the \"Muenke\" group (n=11) or the \"non-Muenke\" control group (n=12) on the basis of a test for the P250R mutation in the FGFR3 gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17414289",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 172,
"text": "P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17103449",
"endSection": "abstract"
},
{
"offsetInBeginSection": 88,
"offsetInEndSection": 279,
"text": "However, Muenke et al. [(1997); Am J Hum Genet 91: 555-564] described a new subgroup carrying the Pro250Arg mutation in the fibroblast growth factor receptor (FGFR) 3 gene on chromosome 4p16.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17036334",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 270,
"text": "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15241680",
"endSection": "abstract"
},
{
"offsetInBeginSection": 323,
"offsetInEndSection": 487,
"text": "In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14963686",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 87,
"text": "Hypochondroplasia (HCH) and Muenke syndrome (MS) are caused by mutations on FGFR3 gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12794698",
"endSection": "abstract"
}
] |
52bf1aa503868f1b06000006 | Is it safe to use Abatacept during pregnancy? | It is not safe to use the drug abatacept during pregnancy, since there is very limited experience/knowledge yet. Additionally, it is recommended to withdraw the drug before pregnancy. | [
"21120498",
"21346578",
"18504282",
"23292481",
"19506586",
"18819772",
"22772888",
"21985166"
] | yesno | [
{
"offsetInBeginSection": 480,
"offsetInEndSection": 777,
"text": "These patients were exposed to rituximab (anti-CD20 monoclonal antibody) or abatacept (fusion protein CTLA4Ig) during the first trimester of their pregnancies. No significant adverse effects or complications were observed during the pregnancies, and all three patients delivered healthy newborns. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23292481",
"endSection": "abstract"
},
{
"offsetInBeginSection": 947,
"offsetInEndSection": 1214,
"text": "Despite these favorable outcomes, the use of these two biological agents must follow international recommendations. Their use is not currently allowed during pregnancy except in cases where the potential benefit to the mother justifies the potential risk to the fetus",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23292481",
"endSection": "abstract"
},
{
"offsetInBeginSection": 951,
"offsetInEndSection": 1265,
"text": "PREGNANCY: Azathioprine, chloroquine, cyclosporin A, prednisolone, sulfasalazine, tacrolimus and cyclophosphamide (only after the second trimester) may be administered during pregnancy. Biologics should be avoided unless there is a treatment need in cases of uncontrolled disease activity.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22772888",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1052,
"offsetInEndSection": 1244,
"text": "As such, it is recommended that abatacept, rituximab and tocilizumab be withheld prior to pregnancy; however, tumour necrosis factor inhibitors and anakinra may be continued until conception. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21985166",
"endSection": "abstract"
},
{
"offsetInBeginSection": 843,
"offsetInEndSection": 926,
"text": "Case reports on abatacept, tocilizumab or anakinra in pregnancy are not conclusive.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21346578",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1111,
"offsetInEndSection": 1333,
"text": "The very limited experience with abatacept, tocilizumab or anakinra in pregnancy allows no statement as to their compatibility with pregnancy. At present use of biological agents throughout pregnancy cannot be recommended.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21346578",
"endSection": "abstract"
},
{
"offsetInBeginSection": 494,
"offsetInEndSection": 642,
"text": "Drugs recommended to be stopped before pregnancy include methotrexate and leflunomide, plus the biologics: anti-TNF agents, rituximab and abatacept.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21120498",
"endSection": "abstract"
},
{
"offsetInBeginSection": 449,
"offsetInEndSection": 641,
"text": "Whereas methotrexate, leflunomide, abatacept and rituximab must be withdrawn before a planned pregnancy, tumor necrosis factor inhibitors and bisphosphonates can be continued until conception.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19506586",
"endSection": "abstract"
},
{
"offsetInBeginSection": 435,
"offsetInEndSection": 604,
"text": "Pregnancy experience with abatacept and rituximab is still too limited to prove their safety for the developing fetus. They must be withdrawn before a planned pregnancy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18504282",
"endSection": "abstract"
},
{
"offsetInBeginSection": 874,
"offsetInEndSection": 976,
"text": "Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept, rituximab, LEF and MMF. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18504282",
"endSection": "abstract"
}
] |
569e7e99ceceede94d000003 | What is DeepCAGE? | The cap analysis of gene expression (CAGE) technology has been established to detect transcriptional starting sites (TSSs) and expression levels by utilizing 5' cDNA tags and PCR. It has been reported that the amount of templates is proportional to the amplification efficiency of PCR. CAGE has been used as a key technique for analyzing promoter activity and finding new transcripts including alternative spliced products and noncoding transcripts. DeepCAGE can be utilized for high-throughput next-generation sequencing technology. DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network. | [
"19074369",
"20967606"
] | summary | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 698,
"text": "The cap analysis of gene expression (CAGE) technology has been established to detect transcriptional starting sites (TSSs) and expression levels by utilizing 5' cDNA tags and PCR. It has been reported that the amount of templates is proportional to the amplification efficiency of PCR. CAGE has been used as a key technique for analyzing promoter activity and finding new transcripts including alternative spliced products and noncoding transcripts. Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology. DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20967606",
"endSection": "abstract"
},
{
"offsetInBeginSection": 311,
"offsetInEndSection": 497,
"text": "Here, we present a new method for high-throughput sequencing of 5' cDNA tags-DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19074369",
"endSection": "abstract"
},
{
"offsetInBeginSection": 869,
"offsetInEndSection": 966,
"text": "DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19074369",
"endSection": "abstract"
},
{
"offsetInBeginSection": 694,
"offsetInEndSection": 804,
"text": "DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20967606",
"endSection": "abstract"
},
{
"offsetInBeginSection": 962,
"offsetInEndSection": 1060,
"text": "DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19074369",
"endSection": "abstract"
},
{
"offsetInBeginSection": 584,
"offsetInEndSection": 721,
"text": "Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20967606",
"endSection": "abstract"
},
{
"offsetInBeginSection": 145,
"offsetInEndSection": 497,
"text": "Mammalian cells have at least 5-10 magnitudes more TSS than previously believed, and deeper sequencing is necessary to detect all active promoters in a given tissue. Here, we present a new method for high-throughput sequencing of 5' cDNA tags-DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19074369",
"endSection": "abstract"
},
{
"offsetInBeginSection": 450,
"offsetInEndSection": 588,
"text": "Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20967606",
"endSection": "abstract"
},
{
"offsetInBeginSection": 742,
"offsetInEndSection": 967,
"text": "Using these data, we present evidence indicating a key role for the Arnt2 transcription factor in hippocampus gene regulation. DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19074369",
"endSection": "abstract"
},
{
"offsetInBeginSection": 456,
"offsetInEndSection": 704,
"text": "Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology. DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20967606",
"endSection": "abstract"
}
] |
56cdf3995795f9a73e00003a | Is STAT3 involved in EIF2AK2-dependent suppression of autophagy? | STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy. However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy | [
"23221979",
"23084476"
] | yesno | [
{
"offsetInBeginSection": 843,
"offsetInEndSection": 1277,
"text": "STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy. However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1279,
"offsetInEndSection": 1527,
"text": "Both STAT3-targeting agents (i.e., Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1588,
"offsetInEndSection": 1806,
"text": "A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1927,
"offsetInEndSection": 2138,
"text": "These results reveal an unsuspected crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 64,
"text": "Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084476",
"endSection": "title"
},
{
"offsetInBeginSection": 371,
"offsetInEndSection": 772,
"text": "The SH2 domain of STAT3 was found to interact with the catalytic domain of the eIF2α kinase 2 EIF2AK2, best known as protein kinase R (PKR). Pharmacological and genetic inhibition of STAT3 stimulated the activating phosphorylation of PKR and consequent eIF2α hyperphosphorylation. Moreover, PKR depletion inhibited autophagy as initiated by chemical STAT3 inhibitors or free fatty acids like palmitate",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084476",
"endSection": "abstract"
},
{
"offsetInBeginSection": 774,
"offsetInEndSection": 960,
"text": "STAT3-targeting chemicals and palmitate caused the disruption of inhibitory STAT3-PKR interactions, followed by PKR-dependent eIF2α phosphorylation, which facilitates autophagy induction",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084476",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1012,
"offsetInEndSection": 1133,
"text": "Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1917,
"offsetInEndSection": 2255,
"text": "A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1588,
"offsetInEndSection": 1925,
"text": "A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 896,
"offsetInEndSection": 1016,
"text": "Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1187,
"offsetInEndSection": 1277,
"text": "However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 82,
"text": "Direct interaction between STAT3 and EIF2AK2 controls fatty acid-induced autophagy",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "title"
},
{
"offsetInBeginSection": 1588,
"offsetInEndSection": 1927,
"text": "A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 896,
"offsetInEndSection": 1018,
"text": "Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 83,
"text": "Direct interaction between STAT3 and EIF2AK2 controls fatty acid-induced autophagy.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "title"
},
{
"offsetInBeginSection": 962,
"offsetInEndSection": 1082,
"text": "These results unravel an unsuspected mechanism of autophagy control that involves STAT3 and PKR as interacting partners.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084476",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1280,
"offsetInEndSection": 1927,
"text": "Both STAT3-targeting agents (i.e., Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula, yet only the latter does so in cell-free systems in vitro. A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1589,
"offsetInEndSection": 2140,
"text": "A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1. These results reveal an unsuspected crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 838,
"offsetInEndSection": 1018,
"text": "Thus, STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 897,
"offsetInEndSection": 1187,
"text": "Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1313,
"offsetInEndSection": 1927,
"text": ", Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula, yet only the latter does so in cell-free systems in vitro. A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979",
"endSection": "abstract"
}
] |
56bc77a3ac7ad10019000015 | RTS S AS01 vaccine was developed to prevent which disease? | RTS,S/AS01 vaccine was developed for prevention of malaria. | [
"19859560",
"25913272",
"25007730",
"21782519",
"24468190",
"23787092",
"25024381",
"21816030",
"21816031",
"23454164",
"19806009",
"21604980",
"22739688",
"21073995",
"20735271",
"21816032",
"25077418",
"24292709",
"25072396"
] | factoid | [
{
"offsetInBeginSection": 188,
"offsetInEndSection": 401,
"text": "This randomized, double-blind study (NCT01323972) assessed consistency of three RTS,S/AS01 malaria vaccine batches formulated from commercial-scale purified antigen bulk lots in terms of anti-CS-responses induced.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25077418",
"endSection": "abstract"
},
{
"offsetInBeginSection": 84,
"offsetInEndSection": 206,
"text": "Until now, only one candidate malaria vaccine RTS,S/AS01 has shown modest protection in phase 3 trial in African infants. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24468190",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 186,
"text": "Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25913272",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 142,
"text": "BACKGROUND: The efficacy and safety of the RTS,S/AS01 candidate malaria vaccine during 18 months of follow-up have been published previously. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25913272",
"endSection": "abstract"
},
{
"offsetInBeginSection": 3356,
"offsetInEndSection": 3546,
"text": "INTERPRETATION: RTS,S/AS01 prevented a substantial number of cases of clinical malaria over a 3-4 year period in young infants and children when administered with or without a booster dose. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25913272",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1163,
"offsetInEndSection": 1376,
"text": "WHO anticipates that the RTS,S/AS01 vaccine will be recommended for the 6-14 week age group for co-administration together with other vaccines as part of routine immunization programs in malaria endemic countries.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22739688",
"endSection": "abstract"
},
{
"offsetInBeginSection": 321,
"offsetInEndSection": 474,
"text": "Recent phase 3 trials with malaria vaccine candidate RTS,S/AS01 (RTS,S) in children has demonstrated modest efficacy against clinical and severe malaria.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24292709",
"endSection": "abstract"
},
{
"offsetInBeginSection": 823,
"offsetInEndSection": 906,
"text": "The RTS,S/AS01(E) malaria vaccine candidate has recently entered phase III testing.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21073995",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 96,
"text": "The efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23454164",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 172,
"text": "Assessment of severe malaria in a multicenter, phase III, RTS, S/AS01 malaria candidate vaccine trial: case definition, standardization of data collection and patient care.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21816031",
"endSection": "title"
},
{
"offsetInBeginSection": 1240,
"offsetInEndSection": 1501,
"text": "If the phase III results confirm the observations made during phase II testing, the RTS,S/AS01(E) vaccine, when broadly implemented and judiciously integrated with other malaria-prevention measures, would have a major public-health impact in sub-Saharan Africa.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21073995",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 81,
"text": "The RTS,S/AS01(E) malaria vaccine candidate has recently entered Phase 3 testing.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19806009",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 153,
"text": "The RTS,S/AS01(E) candidate malaria vaccine is being developed for immunisation of infants in Africa through the expanded programme on immunisation (EPI)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21782519",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "The RTS,S/AS01(E) malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20735271",
"endSection": "abstract"
},
{
"offsetInBeginSection": 161,
"offsetInEndSection": 327,
"text": "Of the multiple approaches that have been pursued, the RTS,S/AS01 vaccine candidate represents the most developed and clinically validated malaria vaccine formulation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21604980",
"endSection": "abstract"
},
{
"offsetInBeginSection": 135,
"offsetInEndSection": 338,
"text": "AS01 has been selected for the clinical development of several candidate vaccines including the RTS,S malaria vaccine and the subunit glycoprotein E varicella zoster vaccine (both currently in phase III)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25024381",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 182,
"text": "Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21782519",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 141,
"text": "A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19859560",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 161,
"text": "Effect of ingested human antibodies induced by RTS, S/AS01 malaria vaccination in children on Plasmodium falciparum oocyst formation and sporogony in mosquitoes.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25007730",
"endSection": "title"
},
{
"offsetInBeginSection": 3196,
"offsetInEndSection": 3546,
"text": "The incidence of generalised convulsive seizures within 7 days of RTS,S/AS01 booster was 2�2 per 1000 doses in young infants and 2�5 per 1000 doses in children.INTERPRETATION: RTS,S/AS01 prevented a substantial number of cases of clinical malaria over a 3-4 year period in young infants and children when administered with or without a booster dose. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25913272",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 136,
"text": "Development of standardized laboratory methods and quality processes for a phase III study of the RTS, S/AS01 candidate malaria vaccine.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21816032",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 152,
"text": "Statistical methodology for the evaluation of vaccine efficacy in a phase III multi-centre trial of the RTS, S/AS01 malaria vaccine in African children.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21816030",
"endSection": "title"
},
{
"offsetInBeginSection": 1579,
"offsetInEndSection": 1932,
"text": "Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively.CONCLUSIONS: RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25072396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 125,
"offsetInEndSection": 1517,
"text": "This article provides a summary of the discussions, conclusions and recommendations from that meeting.Meeting sessions included: a review of the efficacy of artemisinin-based combination therapy in Guyana and Suriname; the outcomes from a consultation on non-malaria febrile illness; the outcomes from the second meeting of the Evidence Review Group on malaria burden estimation; an update on the review of the WHO Guidelines for the Treatment of Malaria; an update regarding progress on the constitution of the vector control Technical Expert Group; updates on the RTS, S/AS01 vaccine and the malaria vaccine technology roadmap; financing and resource allocation for malaria control; malaria surveillance and the need for a surveillance, monitoring and evaluation Technical Expert Group; criteria and classification related to malaria elimination; the next meeting of the Evidence Review Group on Intermittent Preventive Treatment in pregnancy; an update on the soon-to-be launched Elimination Scenario Planning Tool; and an update on the process for the Global Technical Strategy for Malaria Control and Elimination (2016-2025).Policy statements, position statements, and guidelines that arise from the MPAC meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23787092",
"endSection": "abstract"
},
{
"offsetInBeginSection": 213,
"offsetInEndSection": 329,
"text": "the RTS,S/AS01 vaccine candidate represents the most developed and clinically validated malaria vaccine formulation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21604980",
"endSection": "abstract"
}
] |
569e6c68ca240fa209000001 | What are the Topological Domains (TADs)? | Topolological domains or TADs are megabase-sized local chromatin interaction domains which are a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. The boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome. | [
"25274727",
"22495300",
"25409831"
] | summary | [
{
"offsetInBeginSection": 940,
"offsetInEndSection": 1690,
"text": "We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. Finally, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22495300",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 177,
"text": "The human genome is segmented into topologically associating domains (TADs), but the role of this conserved organization during transient changes in gene expression is not known",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25274727",
"endSection": "abstract"
},
{
"offsetInBeginSection": 720,
"offsetInEndSection": 957,
"text": "Recent Hi-C mapping has unveiled substructure within chromatin compartments called topologically associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to replication domains. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25409831",
"endSection": "abstract"
}
] |
56c322d750c68dd416000004 | What is the vibrational theory of olfaction? | The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. The theory proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations. It differs from previous vibrational theories (Dyson, Wright) in providing a detailed and plausible mechanism for biological transduction of molecular vibrations: inelastic electron tunnelling. Thus, the authors, that have proposed this theory, suggest that olfaction, like colour vision and hearing, is a spectral sense. | [
"8985605",
"25901328"
] | summary | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 248,
"text": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25901328",
"endSection": "abstract"
},
{
"offsetInBeginSection": 60,
"offsetInEndSection": 477,
"text": "It proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations. It differs from previous vibrational theories (Dyson, Wright) in providing a detailed and plausible mechanism for biological transduction of molecular vibrations: inelastic electron tunnelling. Elements of the tunnelling spectroscope are identified in putative olfactory receptors and their associated G-protein. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8985605",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1017,
"offsetInEndSection": 1130,
"text": "The evidence presented here suggests instead that olfaction, like colour vision and hearing, is a spectral sense.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8985605",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 446,
"text": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25901328",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 138,
"text": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs),",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25901328",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 249,
"text": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25901328",
"endSection": "abstract"
}
] |
56a375f8496b62f23f000002 | Are CTCF and BORIS involved in genome regulation and cancer? | Yes. CTCF is ubiquitously expressed and plays diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing. CTCF has a single paralogue, the testes-specific CTCF-like gene (CTCFL)/BORIS. CTCF and BORIS can be deregulated in cancer. The tumour suppressor gene CTCF can be mutated or deleted in cancer, or CTCF DNA binding can be altered by epigenetic changes. BORIS is aberrantly expressed frequently in cancer, leading some to propose a pro-tumourigenic role for BORIS. However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation. | [
"16140943",
"17962299",
"16140944",
"21811597",
"21465478",
"24657531",
"23390377",
"12191639"
] | yesno | [
{
"offsetInBeginSection": 61,
"offsetInEndSection": 829,
"text": "CTCF is ubiquitously expressed and plays diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing. CTCF has a single paralogue, the testes-specific CTCF-like gene (CTCFL)/BORIS. CTCF and BORIS can be deregulated in cancer. The tumour suppressor gene CTCF can be mutated or deleted in cancer, or CTCF DNA binding can be altered by epigenetic changes. BORIS is aberrantly expressed frequently in cancer, leading some to propose a pro-tumourigenic role for BORIS. However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24657531",
"endSection": "abstract"
},
{
"offsetInBeginSection": 768,
"offsetInEndSection": 1104,
"text": " The investigation of the molecular mechanisms engaged by CTCF to modulate tumor-related genes emphasizes the cell-type dependency of its tumor suppressor role. Indeed, the ability of CTCF to bind their promoters strictly depends by cell-type features as DNA methylation, BORIS-binding and post-translational modifications as PARYlation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21465478",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1032,
"offsetInEndSection": 1368,
"text": "Moreover, reduction of CTCF in normally BORIS-negative human fibroblasts resulted in derepression of BORIS promoters. These results provide a mechanistic basis for understanding cancer-related associations between haploinsufficiency of CTCF and BORIS derepression, and between the lack of functional p53 and aberrant activation of BORIS",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17962299",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 47,
"text": "CTCF and BORIS in genome regulation and cancer.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24657531",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 104,
"text": "The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12191639",
"endSection": "title"
},
{
"offsetInBeginSection": 2164,
"offsetInEndSection": 2444,
"text": "Collectively, these data indicate that reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter mediates epigenetic regulation of this CT gene in lung cancer cells, and suggest that induction of BORIS may be a novel strategy to augment immunogenicity of pulmonary carcinomas.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16140944",
"endSection": "abstract"
},
{
"offsetInBeginSection": 428,
"offsetInEndSection": 564,
"text": "BORIS is the only known paralog of CTCF, a gene intimately involved in genomic imprinting, chromatin insulation, and nuclear regulation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23390377",
"endSection": "abstract"
},
{
"offsetInBeginSection": 824,
"offsetInEndSection": 1039,
"text": "However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24657531",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2361,
"offsetInEndSection": 2523,
"text": "We suggest that BORIS is likely tethering epigenetic machinery to a novel class of CTCF/BORIS 11ZF target sequences that mediate induction of cancer-testis genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16140943",
"endSection": "abstract"
},
{
"offsetInBeginSection": 471,
"offsetInEndSection": 623,
"text": "Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a \"cancer-testis\" antigen.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21811597",
"endSection": "abstract"
}
] |
56c06ef5ef6e39474100001e | What is the application of the ASSET algorithm in C.elegans? | ASSET (Algorithm for the Segmentation and the Standardization of C. elegans Time-lapse recordings) is a robust algorithm for the automated segmentation and standardization of early Caenorhabditis elegans embryos. It gathers quantitative information with subcellular precision in the early Caenorhabditis elegans embryo, which is an attractive model to investigate evolutionarily conserved cellular mechanisms. ASSET automatically detects the eggshell and the cell cortex from DIC time-lapse recordings of live one-cell-stage embryos and can also track subcellular structures using fluorescent time-lapse microscopy. Importantly, ASSET standardizes the data into an absolute coordinate system to allow robust quantitative comparisons between embryos. | [
"21089077"
] | summary | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 117,
"text": "ASSET: a robust algorithm for the automated segmentation and standardization of early Caenorhabditis elegans embryos.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 1085,
"text": "The early Caenorhabditis elegans embryo is an attractive model to investigate evolutionarily conserved cellular mechanisms. However, there is a paucity of automated methods to gather quantitative information with subcellular precision in this system. We developed ASSET (Algorithm for the Segmentation and the Standardization of C. elegans Time-lapse recordings) to fill this need. ASSET automatically detects the eggshell and the cell cortex from DIC time-lapse recordings of live one-cell-stage embryos and can also track subcellular structures using fluorescent time-lapse microscopy. Importantly, ASSET standardizes the data into an absolute coordinate system to allow robust quantitative comparisons between embryos. We illustrate how ASSET can efficiently gather quantitative data on the motion of centrosomes and precisely track cortical invaginations, revealing hitherto unnoticed differences between wild-type and saps-1(RNAi) embryos. In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1079,
"offsetInEndSection": 1219,
"text": "In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077",
"endSection": "abstract"
},
{
"offsetInBeginSection": 251,
"offsetInEndSection": 722,
"text": "We developed ASSET (Algorithm for the Segmentation and the Standardization of C. elegans Time-lapse recordings) to fill this need. ASSET automatically detects the eggshell and the cell cortex from DIC time-lapse recordings of live one-cell-stage embryos and can also track subcellular structures using fluorescent time-lapse microscopy. Importantly, ASSET standardizes the data into an absolute coordinate system to allow robust quantitative comparisons between embryos. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077",
"endSection": "abstract"
},
{
"offsetInBeginSection": 945,
"offsetInEndSection": 1085,
"text": "In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077",
"endSection": "abstract"
}
] |
5709e947cf1c32585100001d | Are Sidekick proteins members of the immunoglobulin superfamily? | Yes, sidekick are cell adhesion molecules of the immunoglobulin superfamily. | [
"15703275",
"18216854"
] | yesno | [
{
"offsetInBeginSection": 523,
"offsetInEndSection": 708,
"text": "Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18216854",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 183,
"text": "Sidekick-1, a cell adhesion molecule of the immunoglobulin superfamily, is up-regulated in glomerular podocytes in the collapsing glomerulopathy of HIV-associated nephropathy (HIVAN).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15703275",
"endSection": "abstract"
}
] |
553a9aa3f321868558000004 | What are the pyknons? | Using an unsupervised pattern-discovery method, the human intergenic and intronic regions were processed and all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance were catalogued. Among the millions of discovered patterns, a subset of 127,998 patterns was found, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes. The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics. Pyknons might represent a biologically important link between coding and non-coding DNA. | [
"19452047",
"19229130",
"16636294",
"16751093"
] | summary | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 471,
"text": "Using an unsupervised pattern-discovery method, we processed the human intergenic and intronic regions and catalogued all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance. Among the millions of discovered patterns, we found a subset of 127,998 patterns, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16636294",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 231,
"text": "In a recent paper in PNAS, Rigoutsos et al. (2006) describe a nonrandom pattern of repeated elements, called pyknons, which are found more frequently in the 3' untranslated regions of genes than in other regions of the human genome",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16751093",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 211,
"text": "Discovery of pyknons, the most frequent, variable-length DNA sequence motifs in the human genomes, suggests extensive sequence-based connectivity between non-coding and protein-coding components of human genomes",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19229130",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 138,
"text": "Short blocks from the noncoding parts of the human genome have instances within nearly all known genes and relate to biological processes.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16636294",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 417,
"text": "Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes. They are interesting because they portend an unforeseen connection between coding and non-coding DNA. Pyknons have only been discovered in the human genome, so it is unknown whether pyknons have wider biological relevance or are simply a phenomenon of the human genome",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1231,
"offsetInEndSection": 1335,
"text": "these data reveal that pyknons represent a biologically important link between coding and non-coding DNA",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 148,
"text": "Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 147,
"text": "Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047",
"endSection": "abstract"
},
{
"offsetInBeginSection": 473,
"offsetInEndSection": 595,
"text": "The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16636294",
"endSection": "abstract"
}
] |
517a8bab8ed59a060a000040 | Which deiodinases are best known to be present in brain? | All the 3 deiodinases (Type 1, Type 2 and Type 3 deiodinase) are present in the "brain" but Type 1 deiodinase is only found in neurohypophysis that cannot be actually considered true "brain tissue". | [
"22294745",
"16728541",
"8663170",
"7768329",
"10426574",
"22719854",
"12072404",
"8444882",
"15062548",
"1417847"
] | list | [
{
"offsetInBeginSection": 181,
"offsetInEndSection": 307,
"text": "In brain, the presence of type III iodothyronine deiodinase (D3) seems to be important to maintain homeostasis of T(3) levels.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12072404",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1502,
"offsetInEndSection": 1750,
"text": "We were able to detect a protein fragment corresponding to the expected molecular mass (30 kDa) for type III deiodinase by means of Western blot analysis. RT-PCR as well as Northern blot analysis confirmed the presence of D3 mRNA in the cerebellum.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12072404",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 345,
"offsetInEndSection": 583,
"text": "The presence of 5D (type-III) together with our previous report of 5'-deiodinase (type-I in euthyroidism and type-II in hypothyroidism) shows that the isozymes of deiodinases in the neurohypophysis are quite similar to those in the brain.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1417847",
"endSection": "sections.0"
}
] |
5149a61ed24251bc05000044 | What are the computational methods for the prediction of beta-barrel transmembrane proteins? | Computational tools have been developed for beta-barrel transmembrane protein discrimination, topology prediction and prediction of their structural features.
Initial methods developed for the prediction of the transmembrane beta strands were based on hydrophobicity analysis, using sliding windows along the sequence, in order to capture the alternating patterns of hydrophobic-hydrophilic residues of the transmembrane strands, or using generalized secondary structure prediction methods. Other approaches included the construction of special empirical rules using amino-acid propensities and prior knowledge of the structural nature of the proteins, and the development of Neural Network-based predictors to predict the location of alpha-carbon atoms with respect to the membrane. During the last few years, other more refined methods, appeared, including: Neural Networks, Hidden Markov Models, Support Vector Machines, k-Nearest Neighbors, Radial Basis Functions, Bayesian Networks, Genetic Algorithms, Mahalanobis Discriminant Functions, Cellular Automata, N-to-1 Extreme Learning Machines. Hidden Markov Model-based methods are among the most successful in topology prediction, being able to capture the unique architecture of beta-barrel transmembrane proteins. Consensus methods, as well as pipelines of several related tools (e.g. subcellular localization prediciton, alpha-helical transmembrane protein prediction, signal-peptide/lipoprotein prediction) have also used for discriminating beta-barrel transmembrane proteins. Recently, a number of methods for predicting more detailed structural features (e.g. surface accessibility, residue contacts, even detailed atomic 3D models) tailored to beta-barrel transmembrane proteins have been developed, based on knowledge-based potential functions, graph theoretic models, physical models and multi-tape S-attribute grammars. Methods/tools falling in the aforementioned classes are (listed in alphabetical order): BBF (beta-barrel finder), BETAWARE, BOCTOPUS, BOMP, BTMX (Beta barrel TransMembrane eXposure), HHomp, HMM-B2TMR, OMBBpred, PROFtmb, PRED-TMBB, TMB-Hunt, TBBPred, TMBETAPRED-RBF, TMBHMM, TransFold, TMBpro, TMBKNN, Wimley | [
"15647112",
"16844989",
"23530628",
"15980447",
"15162482",
"19153681",
"22148174",
"17597890",
"19429691",
"21328706",
"17520325",
"23297037",
"22540951",
"18989393",
"18006547",
"12192075",
"21935968",
"21426944",
"12169530",
"12070338",
"18218108",
"21967762",
"15141026",
"18467177",
"16858668",
"19421989",
"22247276",
"22987359",
"15070403",
"17597895",
"15769290",
"12798041",
"21064129",
"15215418",
"15215419",
"22031179",
"19470175",
"21531175",
"19622743",
"16225682",
"16674095",
"18312695",
"10698111",
"18355838",
"16597327",
"17088282",
"20488436",
"17958348",
"11274469"
] | list | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 105,
"text": "BETAWARE: a machine-learning tool to detect and predict transmembrane beta-barrel proteins in prokaryotes",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23297037",
"endSection": "title"
},
{
"offsetInBeginSection": 684,
"offsetInEndSection": 1063,
"text": "Recently, we developed two top-performing methods based on machine-learning approaches to tackle both the detection of TMBBs in sets of proteins and the prediction of their topology. Here, we present our BETAWARE program that includes both approaches and can run as a standalone program on a linux-based computer to easily address in-home massive protein annotation or filtering.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23297037",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 618,
"text": "We introduce a graph-theoretic model for predicting the supersecondary structure of transmembrane β-barrel proteins--a particular class of proteins that performs diverse important functions but it is difficult to determine their structure with experimental methods. This ab initio model resolves the protein folding problem based on pseudo-energy minimization with the aid of a simple probabilistic filter. It also allows for determining structures whose barrel follows a given permutation on the arrangement of β-strands, and allows for rapidly discriminating the transmembrane β-barrels from other kinds of proteins.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22987359",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 73,
"text": "BOCTOPUS: improved topology prediction of transmembrane β barrel proteins",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22247276",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 94,
"text": "Improving the detection of transmembrane β-barrel chains with N-to-1 extreme learning machines",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21967762",
"endSection": "title"
},
{
"offsetInBeginSection": 728,
"offsetInEndSection": 833,
"text": "we introduce a new machine learning approach for TMBB detection based on N-to-1 Extreme Learning Machines",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21967762",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 153,
"text": "TMBHMM: a frequency profile based HMM for predicting the topology of transmembrane beta barrel proteins and the exposure status of transmembrane residues",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21426944",
"endSection": "title"
},
{
"offsetInBeginSection": 332,
"offsetInEndSection": 838,
"text": "We present here TMBHMM, a computational method based on a hidden Markov model for predicting the structural topology of putative TMBs from sequence. In addition to predicting transmembrane strands, TMBHMM also predicts the exposure status (i.e., exposed to the membrane or hidden in the protein structure) of the residues in the transmembrane region, which is a novel feature of the TMBHMM method. Furthermore, TMBHMM can also predict the membrane residues that are not part of beta barrel forming strands.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21426944",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 93,
"text": "Prediction of the exposure status of transmembrane beta barrel residues from protein sequence",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21328706",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 244,
"text": "We present BTMX (Beta barrel TransMembrane eXposure), a computational method to predict the exposure status (i.e. exposed to the bilayer or hidden in the protein structure) of transmembrane residues in transmembrane beta barrel proteins (TMBs).",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21328706",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 140,
"text": "Combined prediction of transmembrane topology and signal peptide of beta-barrel proteins: using a hidden Markov model and genetic algorithms",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20488436",
"endSection": "title"
},
{
"offsetInBeginSection": 774,
"offsetInEndSection": 1043,
"text": "We present here, an HMM that combine a transmembrane barrel submodel and an SP submodel for both topology and SP predictions. A new genetic algorithm (GA) is presented here to training the model, at the same time the Posterior-Viterbi algorithm is adopted for decoding.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20488436",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 168,
"offsetInEndSection": 332,
"text": "In this work, we propose a method based on radial basis networks for predicting the number of beta-strands in OMPs and identifying their membrane spanning segments.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19421989",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 624,
"offsetInEndSection": 805,
"text": "We have developed a web server, TMBETAPRED-RBF for predicting the transmembrane beta-strands from amino acid sequence and it is available at http://rbf.bioinfo.tw/~sachen/tmrbf.html",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19421989",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 607,
"text": "We have developed a novel approach for dissecting transmembrane beta-barrel proteins (TMBs) in genomic sequences. The features include (i) the identification of TMBs using the preference of residue pairs in globular, transmembrane helical (TMH) and TMBs, (ii) elimination of globular/TMH proteins that show sequence identity of more than 70% for the coverage of 80% residues with known structures, (iii) elimination of globular/TMH proteins that have sequence identity of more than 60% with known sequences in SWISS-PROT, and (iv) exclusion of TMH proteins using SOSUI, a prediction system for TMH proteins.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17958348",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 113,
"text": "TMBpro: secondary structure, beta-contact and tertiary structure prediction of transmembrane beta-barrel proteins",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18006547",
"endSection": "title"
},
{
"offsetInBeginSection": 732,
"offsetInEndSection": 934,
"text": "We develop a suite (TMBpro) of specialized predictors for predicting secondary structure (TMBpro-SS), beta-contacts (TMBpro-CON) and tertiary structure (TMBpro-3D) of transmembrane beta-barrel proteins.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18006547",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 100,
"offsetInEndSection": 199,
"text": "This paper presents a k-nearest neighbor (K-NN) method for discriminating TMB and non-TMB proteins.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18467177",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 533,
"offsetInEndSection": 1022,
"text": "In this paper, based on the concept of pseudo amino acid composition (PseAA) that can incorporate sequence-order information of a protein sequence so as to remarkably enhance the power of discrete models (Chou, K. C., Proteins: Structure, Function, and Genetics, 2001, 43: 246-255), cellular automata and Lempel-Ziv complexity are introduced to predict the TM regions of integral membrane proteins including both alpha-helical and beta-barrel membrane proteins, validated by jackknife test",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17520325",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 486,
"offsetInEndSection": 737,
"text": "we present BOCTOPUS; an improved method for the topology prediction of TMBs by employing a combination of support vector machines (SVMs) and Hidden Markov Models (HMMs). The SVMs and HMMs account for local and global residue preferences, respectively.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22247276",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 90,
"text": "PRED-TMBB: a web server for predicting the topology of beta-barrel outer membrane proteins",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15215419",
"endSection": "title"
},
{
"offsetInBeginSection": 346,
"offsetInEndSection": 684,
"text": "We present here a web server (PRED-TMBB, http://bioinformatics.biol.uoa.gr/PRED-TMBB) which is capable of predicting the transmembrane strands and the topology of beta-barrel outer membrane proteins of Gram-negative bacteria. The method is based on a Hidden Markov Model, trained according to the Conditional Maximum Likelihood criterion.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15215419",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 92,
"text": "Prediction of transmembrane regions of beta-barrel proteins using ANN- and SVM-based methods",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15162482",
"endSection": "title"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 325,
"text": "his article describes a method developed for predicting transmembrane beta-barrel regions in membrane proteins using machine learning techniques: artificial neural network (ANN) and support vector machine (SVM). The ANN used in this study is a feed-forward neural network with a standard back-propagation training algorithm.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15162482",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 527,
"offsetInEndSection": 845,
"text": "We have also developed an SVM-based method using a primary sequence as input and achieved an accuracy of 77.4%. The SVM model was modified by adding 36 physicochemical parameters to the amino acid sequence information. Finally, ANN- and SVM-based methods were combined to utilize the full potential of both techniques.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15162482",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1190,
"offsetInEndSection": 1291,
"text": "we have developed a Web server, TBBPred, for predicting transmembrane beta-barrel regions in proteins",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15162482",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 50,
"text": "Predicting transmembrane beta-barrels in proteomes",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15141026",
"endSection": "title"
},
{
"offsetInBeginSection": 241,
"offsetInEndSection": 386,
"text": "Here we introduced the design, statistics and results of a novel profile-based hidden Markov model for the prediction and discrimination of TMBs.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15141026",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1381,
"offsetInEndSection": 1453,
"text": "All proteome predictions and the PROFtmb prediction method are available",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15141026",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 135,
"text": "The beta-barrel finder (BBF) program, allowing identification of outer membrane beta-barrel proteins encoded within prokaryotic genomes",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12192075",
"endSection": "title"
},
{
"offsetInBeginSection": 251,
"offsetInEndSection": 795,
"text": "We here report computational analyses of six outer membrane proteins of known 3D structures with respect to (1) secondary structure, (2) hydropathy, and (3) amphipathicity. Using these characteristics, as well as the presence of an N-terminal targeting sequence, a program was developed allowing prediction of integral membrane beta-barrel proteins encoded within any completely sequenced prokaryotic genome. This program, termed the beta-barrel finder (BBF) program, was used to analyze the proteins encoded within the Escherichia coli genome.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12192075",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 92,
"text": "A sequence-profile-based HMM for predicting and discriminating beta barrel membrane proteins",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12169530",
"endSection": "title"
},
{
"offsetInBeginSection": 1003,
"offsetInEndSection": 1485,
"text": "We develop a HMM model, which can predict the topology of beta barrel membrane proteins using, as input, evolutionary information. The model is cyclic with 6 types of states: two for the beta strand transmembrane core, one for the beta strand cap on either side of the membrane, one for the inner loop, one for the outer loop and one for the globular domain state in the middle of each loop. The development of a specific input for HMM based on multiple sequence alignment is novel.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12169530",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 110,
"text": "Prediction of the transmembrane regions of beta-barrel membrane proteins with a neural network-based predictor",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11274469",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 330,
"text": "A method based on neural networks is trained and tested on a nonredundant set of beta-barrel membrane proteins known at atomic resolution with a jackknife procedure. The method predicts the topography of transmembrane beta strands with residue accuracy as high as 78% when evolutionary information is used as input to the network.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11274469",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 570,
"offsetInEndSection": 682,
"text": "A web server based on the proposed method is available at http://yanbioinformatics.cs.usu.edu:8080/TMBKNNsubmit.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18467177",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 94,
"text": "Predicting three-dimensional structures of transmembrane domains of β-barrel membrane proteins",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22148174",
"endSection": "title"
},
{
"offsetInBeginSection": 391,
"offsetInEndSection": 887,
"text": "We have developed a computational method for predicting structures of the transmembrane (TM) domains of β-barrel membrane proteins. Based on physical principles, our method can predict structures of the TM domain of β-barrel membrane proteins of novel topology, including those from eukaryotic mitochondria. Our method is based on a model of physical interactions, a discrete conformational state space, an empirical potential function, as well as a model to account for interstrand loop entropy.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22148174",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 25,
"offsetInEndSection": 93,
"text": "exposure status classification of transmembrane beta barrel residues",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21531175",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 436,
"text": "Several computational methods exist for the identification of transmembrane beta barrel proteins (TMBs) from sequence. Some of these methods also provide the transmembrane (TM) boundaries of the putative TMBs. The aim of this study is to (1) derive the propensities of the TM residues to be exposed to the lipid bilayer and (2) to predict the exposure status (i.e. exposed to the bilayer or hidden in protein structure) of TMB residues.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21531175",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 123,
"text": "The modified Mahalanobis Discriminant for predicting outer membrane proteins by using Chou's pseudo amino acid composition.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18355838",
"endSection": "title"
},
{
"offsetInBeginSection": 224,
"offsetInEndSection": 508,
"text": "In this study, a method that combines increment of diversity with modified Mahalanobis Discriminant, called IDQD, is presented to predict 208 OMPs, 206 transmembrane helical proteins (TMHPs) and 673 globular proteins (GPs) by using Chou's pseudo amino acid compositions as parameters.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18355838",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 88,
"text": "Predicting transmembrane beta-barrels and interstrand residue interactions from sequence",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16858668",
"endSection": "title"
},
{
"offsetInBeginSection": 460,
"offsetInEndSection": 928,
"text": "A novel method using pairwise interstrand residue statistical potentials derived from globular (nonouter membrane) proteins is introduced to predict the supersecondary structure of transmembrane beta-barrel proteins. The algorithm transFold employs a generalized hidden Markov model (i.e., multitape S-attribute grammar) to describe potential beta-barrel supersecondary structures and then computes by dynamic programming the minimum free energy beta-barrel structure.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16858668",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 84,
"text": "Predicting the solvent accessibility of transmembrane residues from protein sequence",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16674095",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 282,
"text": "In this study, we propose a novel method to predict the solvent accessible surface areas of transmembrane residues. For both transmembrane alpha-helix and beta-barrel residues, the correlation coefficients between the predicted and observed accessible surface areas are around 0.65.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16674095",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 120,
"text": "BOMP: a program to predict integral beta-barrel outer membrane proteins encoded within genomes of Gram-negative bacteria",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15215418",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 623,
"text": "This work describes the development of a program that predicts whether or not a polypeptide sequence from a Gram-negative bacterium is an integral beta-barrel outer membrane protein. The program, called the beta-barrel Outer Membrane protein Predictor (BOMP), is based on two separate components to recognize integral beta-barrel proteins. The first component is a C-terminal pattern typical of many integral beta-barrel proteins. The second component calculates an integral beta-barrel score of the sequence based on the extent to which the sequence contains stretches of amino acids typical of transmembrane beta-strands.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15215418",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 88,
"text": "A HMM-based method to predict the transmembrane regions of beta-barrel membrane proteins",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12798041",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 218,
"text": "A novel method is developed to model and predict the transmembrane regions of beta-barrel membrane proteins. It is based on a Hidden Markov model (HMM) with architecture obeying those proteins' construction principles.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12798041",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 271,
"offsetInEndSection": 649,
"text": "First, an algorithm that calculates the mean hydrophobicity of one side of putative beta-strands predicted the positions of 16 transmembrane segments, a structure common to known porins. Second, outer loops typical of porins were assigned using an artificial neural network trained to predict the topology of bacterial outer-membrane proteins with a predominance of beta-strands",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12070338",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 97,
"text": "Prediction of the membrane-spanning beta-strands of the major outer membrane protein of Chlamydia",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12070338",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 179,
"text": "Topology prediction of Brucella abortus Omp2b and Omp2a porins after critical assessment of transmembrane beta strands prediction by several secondary structure prediction methods",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10698111",
"endSection": "title"
},
{
"offsetInBeginSection": 162,
"offsetInEndSection": 671,
"text": "Four porins of known structure were selected as test-cases and their secondary structure delineated. The specificity and sensitivity of 11 methods were separately evaluated. Our critical assessment shows that some secondary structure prediction methods (PHD, Dsc, Sopma) originally designed to predict globular protein structure are useful on porin topology prediction. The overall best prediction is obtained by combining these three \"generalist\" methods with a transmembrane beta strand prediction technique",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10698111",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 119,
"text": "A knowledge-based potential highlights unique features of membrane α-helical and β-barrel protein insertion and folding",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22031179",
"endSection": "title"
},
{
"offsetInBeginSection": 323,
"offsetInEndSection": 796,
"text": "In previous work, a depth-dependent insertion potential, E(z) , was derived for α-helical inner membrane proteins. We have generated an equivalent potential for TM β-barrel proteins. The similarities and differences between these two potentials provide insight into unique aspects of the folding and insertion of β-barrel membrane proteins. This potential can predict orientation within the membrane and identify functional residues involved in intermolecular interactions.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22031179",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 146,
"text": "Improved identification of outer membrane beta barrel proteins using primary sequence, predicted secondary structure, and evolutionary information",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21064129",
"endSection": "title"
},
{
"offsetInBeginSection": 759,
"offsetInEndSection": 1035,
"text": "We present an accurate sequence-based predictor of OMBBs, called OMBBpred, which utilizes a Support Vector Machine classifier and a custom-designed set of 34 novel numerical descriptors derived from predicted secondary structures, hydrophobicity, and evolutionary information.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21064129",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 140,
"text": "Predicting weakly stable regions, oligomerization state, and protein-protein interfaces in transmembrane domains of outer membrane proteins.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19622743",
"endSection": "title"
},
{
"offsetInBeginSection": 884,
"offsetInEndSection": 1461,
"text": "We have also discovered that out-clamps, in-plugs, and oligomerization are 3 general mechanisms for stabilizing weakly stable TM regions. In addition, we have found that extended and contiguous weakly stable regions often signal the existence of an oligomer and that strands located in the interfaces of protein-protein interactions are considerably less stable. Based on these observations, we can predict oligomerization states and can identify the interfaces of protein-protein interactions for beta-barrel membrane proteins by using either structure or sequence information",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19622743",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 688,
"offsetInEndSection": 870,
"text": "Recently, we developed two top-performing methods based on machine-learning approaches to tackle both the detection of TMBBs in sets of proteins and the prediction of their topology.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23297037",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 265,
"text": "We introduce a graph-theoretic model for predicting the supersecondary structure of transmembrane β-barrel proteins--a particular class of proteins that performs diverse important functions but it is difficult to determine their structure with experimental methods.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22987359",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 508,
"offsetInEndSection": 609,
"text": "Several computational methods have been developed to discriminate TMBBs from other types of proteins.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21967762",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 563,
"offsetInEndSection": 711,
"text": "To conquer this limitation, we developed a new computational model that can be used for predicting the ASA of both TM α-helix and β-barrel residues.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21935968",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 117,
"text": "Transmembrane beta barrel (TMB) proteins are found in the outer membranes of bacteria, mitochondria and chloroplasts.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21426944",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 765,
"offsetInEndSection": 899,
"text": "RESULTS: We present here, an HMM that combine a transmembrane barrel submodel and an SP submodel for both topology and SP predictions.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20488436",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 167,
"text": "Prediction of membrane spanning segments in beta-barrel outer membrane proteins (OMP) and their topology is an important problem in structural and functional genomics.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19421989",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 331,
"offsetInEndSection": 531,
"text": "In the simplest of these, the target \"model\" is another protein sequence, while the more elaborate methods group together the entire set of t ansmembrane helical or transmembrane beta-barrel proteins.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19153681",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1169,
"offsetInEndSection": 1348,
"text": "Based on this study, we have developed a Web server, TBBPred, for predicting transmembrane beta-barrel regions in proteins (available at http://www.imtech.res.in/raghava/tbbpred).",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15162482",
"endSection": "sections.0"
}
] |
56b8a525156496395c000002 | Describe what is the usage of the Theatre software tool for genomic analysis. | Theatre is a web-based computing system designed for the comparative analysis of genomic sequences, especially with respect to motifs likely to be involved in the regulation of gene expression. Theatre is an interface to commonly used sequence analysis tools and biological sequence databases to determine or predict the positions of coding regions, repetitive sequences and transcription factor binding sites in families of DNA sequences. The information is displayed in a manner that can be easily understood and can reveal patterns that might not otherwise have been noticed. In addition to web-based output, Theatre can produce publication quality colour hardcopies showing predicted features in aligned genomic sequences. | [
"12824356"
] | summary | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 726,
"text": "Theatre is a web-based computing system designed for the comparative analysis of genomic sequences, especially with respect to motifs likely to be involved in the regulation of gene expression. Theatre is an interface to commonly used sequence analysis tools and biological sequence databases to determine or predict the positions of coding regions, repetitive sequences and transcription factor binding sites in families of DNA sequences. The information is displayed in a manner that can be easily understood and can reveal patterns that might not otherwise have been noticed. In addition to web-based output, Theatre can produce publication quality colour hardcopies showing predicted features in aligned genomic sequences.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12824356",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 97,
"text": "Theatre: A software tool for detailed comparative analysis and visualization of genomic sequence.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12824356",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 440,
"text": "Theatre is a web-based computing system designed for the comparative analysis of genomic sequences, especially with respect to motifs likely to be involved in the regulation of gene expression. Theatre is an interface to commonly used sequence analysis tools and biological sequence databases to determine or predict the positions of coding regions, repetitive sequences and transcription factor binding sites in families of DNA sequences. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12824356",
"endSection": "abstract"
}
] |
56f3eebd2ac5ed1459000016 | How are CRM (cis-regulatory modules) defined? | Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules. | [
"25268582",
"15757364",
"21152003",
"14534164",
"17711474",
"15883375",
"25442502",
"19820186",
"15215390",
"22877946",
"23409927",
"15677727",
"16980320",
"22492356",
"19660565"
] | summary | [
{
"offsetInBeginSection": 137,
"offsetInEndSection": 281,
"text": "Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15215390",
"endSection": "abstract"
},
{
"offsetInBeginSection": 133,
"offsetInEndSection": 303,
"text": "In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15883375",
"endSection": "abstract"
},
{
"offsetInBeginSection": 474,
"offsetInEndSection": 604,
"text": "This conserved sequence has therefore been proposed to act as a long-range, cis-acting regulator of limb-specific Shh expression. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15677727",
"endSection": "abstract"
},
{
"offsetInBeginSection": 975,
"offsetInEndSection": 1187,
"text": "The conserved upstream sequence can activate gene expression from basal promoters in the brain vesicle, although it requires additional cis-regulatory sequences to fully activate the CNS-specific gene expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17711474",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 136,
"text": "The genomic instructions used to regulate development are encoded within a set of functional DNA elements called cis-regulatory modules ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19660565",
"endSection": "abstract"
},
{
"offsetInBeginSection": 282,
"offsetInEndSection": 404,
"text": "Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25268582",
"endSection": "abstract"
},
{
"offsetInBeginSection": 471,
"offsetInEndSection": 714,
"text": "However, studies on the cis-regulatory sequences mediating the synergistic effects of these transcription factors are complicated by the limited knowledge of notochord genes and cis-regulatory modules (CRMs) that are directly targeted by both.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19820186",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 316,
"text": "The identification of transcription factor binding sites (TFBSs) and cis-regulatory modules (CRMs) is a crucial step in studying gene expression, but the computational method attempting to distinguish CRMs from NCNRs still remains a challenging problem due to the limited knowledge of specific interactions involved.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23409927",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 234,
"text": "In eukaryotes, transcriptional regulation is usually mediated by interactions of multiple transcription factors (TFs) with their respective specific cis-regulatory elements (CREs) in the so-called cis-regulatory modules (CRMs) in DNA.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25442502",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 201,
"text": "The transcriptional regulation of a metazoan gene depends on the cooperative action of multiple transcription factors that bind to cis-regulatory modules (CRMs) located in the neighborhood of the gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14534164",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann-Mangold organizer.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22492356",
"endSection": "title"
},
{
"offsetInBeginSection": 631,
"offsetInEndSection": 756,
"text": "We also identified potential cis-regulatory modules (CRMs) defined as clusters of conserved TFBSs in the entire mouse genome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16980320",
"endSection": "abstract"
}
] |
54cb9c94f693c3b16b000005 | Which is the main regulatory molecule of SERCA2A function in the cardiac muscle? | SERCA2a activity is regulated by phosphorylation of another SR protein, Phospholamban (PLN). Phospholamban (PLB) inhibits the activity of SERCA2a, the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum, by decreasing the apparent affinity of the enzyme for Ca(2+). | [
"23710633",
"25451386",
"19112098",
"18971376",
"19948724",
"10555147",
"21266500",
"18415121",
"18508637",
"11371203",
"15598648"
] | factoid | [
{
"offsetInBeginSection": 406,
"offsetInEndSection": 705,
"text": "SR Ca-transport is mediated by the SR Ca-ATPase (SERCA2a) and its regulatory phosphoprotein, phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA2a and phosphorylation by protein kinase A (PKA) or calcium-calmodulin-dependent protein kinases (CAMKII) relieves these inhibitory effects.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25451386",
"endSection": "abstract"
},
{
"offsetInBeginSection": 874,
"offsetInEndSection": 976,
"text": "SERCA2a activity can be regulated at multiple levels of a signaling cascade comprised of phospholamban",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23710633",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 193,
"text": "Phospholamban (PLN), the reversible inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), is a key regulator of myocyte Ca(2+) cycling with a significant role in heart failure.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21266500",
"endSection": "abstract"
},
{
"offsetInBeginSection": 97,
"offsetInEndSection": 271,
"text": "The sarco(endo)plasmic reticulum (SR) Ca(2+) transport ATPase (SERCA2a) and its inhibitor phospholamban (PLN) control the uptake of Ca(2+) by SR membranes during relaxation. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18971376",
"endSection": "abstract"
},
{
"offsetInBeginSection": 687,
"offsetInEndSection": 762,
"text": "phospholamban (PLN), a muscle-specific SR Ca(2+)-ATPase (SERCA2a) inhibitor",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15598648",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 156,
"text": "Phospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, and functions as an endogenous inhibitor of Ca-ATPase transport activity.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11371203",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 168,
"text": "Phospholamban (PLB) inhibits the activity of SERCA2a, the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum, by decreasing the apparent affinity of the enzyme for Ca(2+).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19948724",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 214,
"text": "Phospholamban has been suggested to be a key regulator of cardiac sarcoplasmic reticulum (SR) Ca cycling and contractility and a potential therapeutic target in restoring the depressed Ca cycling in failing hearts.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19112098",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1269,
"offsetInEndSection": 1304,
"text": "phospholamban regulation of SERCA2a",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19112098",
"endSection": "abstract"
},
{
"offsetInBeginSection": 181,
"offsetInEndSection": 530,
"text": "SERCA2a activity is regulated by phosphorylation of another SR protein: Phospholamban (PLN). Dephosphorylated PLN inhibits SERCA2a. Phosphorylation of PLN by either cAMP or cGMP-dependent protein kinase at Ser16 or the Ca2+-calmodulin-dependent protein kinase (CaMKII), at Thr17, relieves this inhibition, increasing SR Ca2+ uptake and SR Ca2+ load.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18508637",
"endSection": "abstract"
},
{
"offsetInBeginSection": 358,
"offsetInEndSection": 532,
"text": "The ablation of a muscle-specific sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) inhibitor, phospholamban, rescued the spectrum of phenotypes that resemble human heart failure.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10555147",
"endSection": "abstract"
},
{
"offsetInBeginSection": 286,
"offsetInEndSection": 495,
"text": "The sarco(endo)plasmic reticulum Ca(2+) transport adenosine triphosphatase (SERCA2a) and its regulator phospholamban (PLN) have a central role in modulating Ca(2+) homeostasis and, therefore, cardiac function.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18415121",
"endSection": "abstract"
}
] |
5519113b622b19434500000f | Which gene is responsible for the development of the Mowat-Wilson syndrome? | Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. | [
"15908750",
"21336163",
"24282181",
"19842203",
"17932455",
"24092421",
"17203459",
"23523603",
"16688751",
"24029077",
"17103451",
"23427518",
"23466526",
"11891681",
"15006694",
"14681759",
"20125191",
"17478475"
] | factoid | [
{
"offsetInBeginSection": 219,
"offsetInEndSection": 275,
"text": "The cause of MWS is a de novo mutation in the ZEB2 gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23427518",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 171,
"text": "zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 160,
"text": "Intrahepatic biliary anomalies in a patient with Mowat-Wilson syndrome uncover a role for the zinc finger homeobox gene zfhx1b in vertebrate biliary development",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163",
"endSection": "title"
},
{
"offsetInBeginSection": 458,
"offsetInEndSection": 565,
"text": "We used the zebrafish model system to determine whether zfhx1b has a role in vertebrate biliary development",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 133,
"text": "Comprehensive ZEB2 gene analysis for Mowat-Wilson syndrome in a North American cohort: a suggested approach to molecular diagnostics.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 94,
"text": "A case of Mowat-Wilson syndrome caused by a truncating mutation within exon 8 of the ZEB2 gene",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23427518",
"endSection": "title"
},
{
"offsetInBeginSection": 456,
"offsetInEndSection": 602,
"text": "All typical cases result from haploinsufficiency of the ZEB2 (also known as ZFHX1B or SIP-1) gene, with over 100 distinct mutations now described.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203",
"endSection": "abstract"
},
{
"offsetInBeginSection": 603,
"offsetInEndSection": 774,
"text": "Approximately 80% of patients have a nonsense or frameshift mutation detectable by sequencing, with the rest having gross deletions necessitating a dosage sensitive assay.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1039,
"offsetInEndSection": 1127,
"text": "Six patients had deletions in the ZEB2 gene, including two novel partial gene deletions.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1128,
"offsetInEndSection": 1373,
"text": "This report, the first such analysis in North American patients, adds to the growing list of both novel pathogenic mutations associated with MWS, as well as other variants in the ZEB2 gene. In addition, we suggest an economical testing strategy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Nonsense mutations of the ZFHX1B gene in two Japanese girls with Mowat-Wilson syndrome",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17932455",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 153,
"text": "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17932455",
"endSection": "abstract"
},
{
"offsetInBeginSection": 790,
"offsetInEndSection": 915,
"text": "According to the gene analysis using white blood cells, they had nonsense mutations in ZFHX1B, R695X and Q433X, respectively.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17932455",
"endSection": "abstract"
},
{
"offsetInBeginSection": 916,
"offsetInEndSection": 1074,
"text": "In conclusion, molecular genetic analysis of ZFHX1B is important for a definite diagnosis of MWS which has a wide phenotypic spectrum of congenital anomalies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17932455",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 98,
"text": "A missense mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16688751",
"endSection": "title"
},
{
"offsetInBeginSection": 332,
"offsetInEndSection": 638,
"text": "Mutations leading to haploinsufficiency of the ZFHX1B gene have been described as the underlying cause of this condition. We report on the clinical findings in a 2(1/2)-year-old boy with some aspects out of the MWS-spectrum in addition to unusual anomalies and a novel missense mutation in the ZFHX1B gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16688751",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 118,
"text": "Genitourinary anomalies in Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B).",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15908750",
"endSection": "title"
},
{
"offsetInBeginSection": 422,
"offsetInEndSection": 500,
"text": "It is caused by mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15908750",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 172,
"text": "Pleiotropic and diverse expression of ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the \"Mowat-Wilson\" syndrome",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15006694",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "ZFHX1B encodes Smad-interacting protein 1, a transcriptional corepressor involved in the transforming growth factors beta (TGFbeta) signaling pathway",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15006694",
"endSection": "abstract"
},
{
"offsetInBeginSection": 151,
"offsetInEndSection": 287,
"text": "ZFHX1B mutations cause a complex developmental phenotype characterized by severe mental retardation (MR) and multiple congenital defects",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15006694",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 119,
"text": "Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome)",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14681759",
"endSection": "title"
},
{
"offsetInBeginSection": 188,
"offsetInEndSection": 440,
"text": "Mutation analysis of the zinc finger homeo box 1 B (ZFHX1 B) gene revealed a de novo 7 bp deletion (TGGCCCC) at nucleotide 1773 (1773 delTGGCCCC) resulting in a frameshift and leading to a termination codon at amino acid residue 604 (604 X) in exon 8 C",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14681759",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 204,
"text": "\"Mowat-Wilson\" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11891681",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 390,
"text": "Recently mutations in the gene ZFHX1B (SIP1) were shown in patients with \"syndromic Hirschsprung disease\" with mental retardation (MR) and multiple congenital anomalies (MCA), but it was unclear if Hirschsprung disease is an obligate symptom of these mutations and if the distinct facial phenotype delineated by Mowat et al. [1998: J Med Genet 35: 617-623] is specific for ZFHX1B mutations.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11891681",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 161,
"text": "Intrahepatic biliary anomalies in a patient with Mowat-Wilson syndrome uncover a role for the zinc finger homeobox gene zfhx1b in vertebrate biliary development.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163",
"endSection": "title"
},
{
"offsetInBeginSection": 117,
"offsetInEndSection": 294,
"text": "Haploinsufficiency of a gene termed ZFHX1B (also known as SIP1) on chromosome 2 is responsible for this condition, and clinical genetic testing for MWS recently became available",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17103451",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 333,
"text": "Mowat-Wilson syndrome is a recently delineated autosomal dominant developmental anomaly, whereby heterozygous mutations in the ZFHX1B gene cause mental retardation, delayed motor development, epilepsy and a wide spectrum of clinically heterogeneous features, suggestive of neurocristopathies at the cephalic, cardiac and vagal levels",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17478475",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 159,
"text": "zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 56,
"text": "ZFHX1B mutations in patients with Mowat-Wilson syndrome.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17203459",
"endSection": "title"
},
{
"offsetInBeginSection": 923,
"offsetInEndSection": 1119,
"text": "A similar issue of differential diagnosis was raised by a large 4.3 Mb 2q22.3q23.1 deletion encompassing ZEB2, the gene responsible for the Mowat-Wilson syndrome, whose signs may overlap with RSTS",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20125191",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24282181",
"endSection": "abstract"
},
{
"offsetInBeginSection": 207,
"offsetInEndSection": 377,
"text": "At molecular level, MWS is characterized by many different described mutations in the zinc finger E-box protein 2 (ZEB2) gene, ultimately leading to loss of gene function",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24092421",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 232,
"text": "Individuals with Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic facial features, a variety of congenital anomalies such as Hirschsprung disease, and intellectual disabilities caused by mutation or deletion of ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24029077",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 182,
"text": "Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene rarely diagnosed prenatally and with little fetal description reported",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23523603",
"endSection": "abstract"
},
{
"offsetInBeginSection": 290,
"offsetInEndSection": 354,
"text": "MWS is caused by de novo heterozygous mutations in the ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23466526",
"endSection": "abstract"
}
] |
531d6bfc267d7dd053000007 | How is active neurotoxin of Clostridium botulinum detected? | Active neurotoxin of Clostridium botulinum can be detected by:
mouse lethality assay
by mass spectrometry
bioassay
differentiated cell models
peptide cleavage assay
FDC (functional dual coating) microtitre plate immuno-biochemical assay
endopeptidase activity monitored via UV-Visible spectroscopy | [
"23925142",
"22223483",
"18571757",
"7989542",
"23518650",
"16318699",
"23181535",
"23239357",
"16614251"
] | list | [
{
"offsetInBeginSection": 513,
"offsetInEndSection": 577,
"text": "The neurotoxin detection is based on the mouse lethality assay. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16614251",
"endSection": "abstract"
},
{
"offsetInBeginSection": 753,
"offsetInEndSection": 841,
"text": "which could be shown by bioassay to produce biologically active type B toxin in culture.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7989542",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 148,
"text": "Human induced pluripotent stem cells (hiPSC) hold great promise for providing various differentiated cell models for in vitro toxigenicity testing. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22223483",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1398,
"offsetInEndSection": 1535,
"text": "A direct comparison of BoNT detection using primary rat spinal cord cells and hiPSC-derived neurons showed equal or increased sensitivity",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22223483",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1043,
"offsetInEndSection": 1218,
"text": "BoNT/A intoxication studies demonstrate that the hiPSC-derived neurons reproducibly and quantitatively detect biologically active BoNT/A with high sensitivity (EC(50) ∼0.3 U).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22223483",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1655,
"offsetInEndSection": 1847,
"text": " these data suggest that neurons derived from hiPSCs provide an ideal and highly sensitive platform for BoNT potency determination, neutralizing antibody detection and for mechanistic studies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22223483",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 79,
"text": "Detection of botulinum neurotoxin-A activity in food by peptide cleavage assay.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18571757",
"endSection": "title"
},
{
"offsetInBeginSection": 354,
"offsetInEndSection": 535,
"text": "his study reports the successful use of an enzymatic assay employing an internally quenched fluorogenic peptide as a fast, simple and inexpensive alternative to the mouse bioassay. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18571757",
"endSection": "abstract"
},
{
"offsetInBeginSection": 512,
"offsetInEndSection": 537,
"text": "BoNT endopeptidase assays",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23181535",
"endSection": "abstract"
},
{
"offsetInBeginSection": 708,
"offsetInEndSection": 797,
"text": "in vivo mouse bioassay has for years been the 'gold standard' assay used for this purpose",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23239357",
"endSection": "abstract"
},
{
"offsetInBeginSection": 903,
"offsetInEndSection": 1073,
"text": "Cell-based assays are currently the only in vitro alternative that detect fully functional BoNTs in a single assay and have been utilized for years for research purposes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23239357",
"endSection": "abstract"
},
{
"offsetInBeginSection": 422,
"offsetInEndSection": 514,
"text": "mouse bioassay (MBA) is traditionally used to confirm the presence of toxin in serum or food",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23518650",
"endSection": "abstract"
},
{
"offsetInBeginSection": 625,
"offsetInEndSection": 705,
"text": "A novel FDC (functional dual coating) microtitre plate immuno-biochemical assay,",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23518650",
"endSection": "abstract"
},
{
"offsetInBeginSection": 374,
"offsetInEndSection": 762,
"text": "This report demonstrates a novel assay that utilises the endopeptidase activity of the toxin to detect Botulinum neurotoxin in a pharmaceutical sample. The cleaving of SNAP-25 is monitored via UV-Visible spectroscopy with a limit of detection of 373 fg/mL and has been further developed into a high throughput method using a microplate reader detecting down to 600 fg/mL of active toxin. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23925142",
"endSection": "abstract"
}
] |
56d19a363975bb303a000017 | Which factor interacts with Treslin/TICRR throughout the cell cycle of human cells? | MDM two binding protein (MTBP) is a factor that interacts with Treslin/TICRR throughout the cell cycle. MTBP depletion by means of small interfering RNA inhibits DNA replication by preventing assembly of the CMG (Cdc45-MCM-GINS) holohelicase during origin firing. Although MTBP has been implicated in the function of the p53 tumor suppressor, it is required for DNA replication irrespective of a cell's p53 status. MTBP is proposed to act with Treslin/TICRR to integrate signals from cell cycle and DNA damage response pathways to control the initiation of DNA replication in human cells. | [
"23704573"
] | factoid | [
{
"offsetInBeginSection": 289,
"offsetInEndSection": 917,
"text": "We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR throughout the cell cycle. We show that MTBP depletion by means of small interfering RNA inhibits DNA replication by preventing assembly of the CMG (Cdc45-MCM-GINS) holohelicase during origin firing. Although MTBP has been implicated in the function of the p53 tumor suppressor, we found MTBP is required for DNA replication irrespective of a cell's p53 status. We propose that MTBP acts with Treslin/TICRR to integrate signals from cell cycle and DNA damage response pathways to control the initiation of DNA replication in human cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23704573",
"endSection": "abstract"
},
{
"offsetInBeginSection": 289,
"offsetInEndSection": 405,
"text": "We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR throughout the cell cycle",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23704573",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 407,
"text": "Treslin/TICRR (TopBP1-interacting, replication stimulating protein/TopBP1-interacting, checkpoint, and replication regulator), the human ortholog of the yeast Sld3 protein, is an essential DNA replication factor that is regulated by cyclin-dependent kinases and the DNA damage checkpoint. We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR throughout the cell cycle.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23704573",
"endSection": "abstract"
}
] |
56ecffd62ac5ed1459000003 | What is oprozomib? | Oprozomib is a second-generation, highly-selective, orally administered proteasome inhibitor with promising activity against multiple myeloma.
Oprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. Oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice. Consequently, oprozomib seems to be able to effectively shift the bone microenvironment from a catabolic to an anabolic state and, similar to bortezomib, may decrease skeletal complications of MM.
Oprozomib effectively decreases multiple myeloma cell viability.
Oprozomib potently inhibit cell survival and induce apoptosis in HNSCC cell lines via upregulation of pro-apoptotic Bik. Upregulation of Mcl-1 by these agents served to dampen their efficacies. Oprozomib also induced autophagy, mediated, in part, by activation of the UPR pathway involving upregulation of ATF4 transcription factor. Autophagy induction served a prosurvival role. Oral administration of ONX 0912 inhibited the growth of HNSCC xenograft tumors in a dose-dependent manner.
Oprozomib inhibited NF-κB expression. | [
"24915039",
"24471924",
"22763387",
"24712303",
"24135407",
"22929803",
"24103732",
"24239172",
"22995770",
"25005844",
"25935605"
] | summary | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 159,
"text": "Carfilzomib and ONX 0912 inhibit cell survival and tumor growth of head and neck cancer and their activities are enhanced by suppression of Mcl-1 or autophagy.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22929803",
"endSection": "title"
},
{
"offsetInBeginSection": 162,
"offsetInEndSection": 221,
"text": "ONX 0912 (oprozomib) is an orally bioavailable derivative. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22929803",
"endSection": "abstract"
},
{
"offsetInBeginSection": 865,
"offsetInEndSection": 1356,
"text": "Carfilzomib and ONX 0912 potently induced apoptosis in HNSCC cell lines via upregulation of pro-apoptotic Bik. Upregulation of Mcl-1 by these agents served to dampen their efficacies. Carfilzomib and ONX 0912 also induced autophagy, mediated, in part, by activation of the UPR pathway involving upregulation of ATF4 transcription factor. Autophagy induction served a prosurvival role. Oral administration of ONX 0912 inhibited the growth of HNSCC xenograft tumors in a dose-dependent manner.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22929803",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1369,
"offsetInEndSection": 1689,
"text": "These results show that carfilzomib and ONX 0912 are potently active against HNSCC cells, and the activities of these agents can be enhanced via suppression of Mcl-1 or inhibition of autophagy. Oral ONX 0912 exhibits in vivo activity against HNSCC tumors and may represent a useful therapeutic agent for this malignancy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22929803",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 155,
"text": "The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770",
"endSection": "title"
},
{
"offsetInBeginSection": 383,
"offsetInEndSection": 1276,
"text": "We recently reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors. Both compounds promote upregulation of proapoptotic BIK and antiapoptotic MCL1, which serves to mediate and attenuate, respectively, the killing activities of these proteasome inhibitors. Both compounds also induce complete autophagic flux that is partially dependent on activation of the unfolded protein response (UPR) and upregulation of ATF4. Carfilzomib- and oprozomib-induced autophagy acts to promote HNSCC cell survival. Our study indicates that the therapeutic benefit of these promising proteasome inhibitors may be improved by inhibiting MCL1 expression or autophagy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770",
"endSection": "abstract"
},
{
"offsetInBeginSection": 366,
"offsetInEndSection": 543,
"text": "Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387",
"endSection": "abstract"
},
{
"offsetInBeginSection": 797,
"offsetInEndSection": 1547,
"text": "At clinically relevant concentrations, carfilzomib and oprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. Accordingly, carfilzomib and oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice. Finally, in mouse models of disseminated MM, the epoxyketone-based PIs decreased murine 5TGM1 and human RPMI-8226 tumor burden and prevented bone loss. These data demonstrate that, in addition to anti-myeloma properties, carfilzomib and oprozomib effectively shift the bone microenvironment from a catabolic to an anabolic state and, similar to bortezomib, may decrease skeletal complications of MM.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387",
"endSection": "abstract"
},
{
"offsetInBeginSection": 968,
"offsetInEndSection": 1234,
"text": "Finally, we found that DC incubation with the drug(s) enhanced IκB expression and that oprozomib inhibited NF-κB expression. We concluded that based on its activity and oral bioavailability, oprozomib merits further investigation in an animal GvHD prevention model. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24103732",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 168,
"text": "Carfilzomib and oprozomib synergize with histone deacetylase inhibitors in head and neck squamous cell carcinoma models of acquired resistance to proteasome inhibitors.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039",
"endSection": "title"
},
{
"offsetInBeginSection": 123,
"offsetInEndSection": 254,
"text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039",
"endSection": "abstract"
},
{
"offsetInBeginSection": 725,
"offsetInEndSection": 1071,
"text": "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24471924",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1119,
"offsetInEndSection": 1200,
"text": "Carfilzomib- and oprozomib-induced autophagy acts to promote HNSCC cell survival.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770",
"endSection": "abstract"
},
{
"offsetInBeginSection": 796,
"offsetInEndSection": 882,
"text": "Further, new orally administered second-generation PI oprozomib is being investigated.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24712303",
"endSection": "abstract"
},
{
"offsetInBeginSection": 253,
"offsetInEndSection": 384,
"text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1142,
"offsetInEndSection": 1295,
"text": "Accordingly, carfilzomib and oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387",
"endSection": "abstract"
},
{
"offsetInBeginSection": 540,
"offsetInEndSection": 716,
"text": "Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1085,
"offsetInEndSection": 1209,
"text": "Finally, we found that DC incubation with the drug(s) enhanced IκB expression and that oprozomib inhibited NF-κB expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24103732",
"endSection": "abstract"
},
{
"offsetInBeginSection": 693,
"offsetInEndSection": 787,
"text": "Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 154,
"text": "The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 173,
"text": "The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387",
"endSection": "title"
},
{
"offsetInBeginSection": 715,
"offsetInEndSection": 800,
"text": "Further, new orally administered second-generation PI oprozomib is being investigated",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24712303",
"endSection": "abstract"
},
{
"offsetInBeginSection": 725,
"offsetInEndSection": 1070,
"text": "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24471924",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 174,
"text": "The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387",
"endSection": "title"
},
{
"offsetInBeginSection": 383,
"offsetInEndSection": 698,
"text": "We recently reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770",
"endSection": "abstract"
},
{
"offsetInBeginSection": 994,
"offsetInEndSection": 1148,
"text": "Accordingly, carfilzomib and oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387",
"endSection": "abstract"
},
{
"offsetInBeginSection": 797,
"offsetInEndSection": 994,
"text": "At clinically relevant concentrations, carfilzomib and oprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387",
"endSection": "abstract"
},
{
"offsetInBeginSection": 603,
"offsetInEndSection": 698,
"text": "Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770",
"endSection": "abstract"
},
{
"offsetInBeginSection": 123,
"offsetInEndSection": 255,
"text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1045,
"offsetInEndSection": 1127,
"text": "Carfilzomib- and oprozomib-induced autophagy acts to promote HNSCC cell survival. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770",
"endSection": "abstract"
},
{
"offsetInBeginSection": 124,
"offsetInEndSection": 428,
"text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. However, the mechanisms of acquired resistance to carfilzomib and oprozomib are incompletely understood, and effective strategies for overcoming this resistance are needed.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039",
"endSection": "abstract"
},
{
"offsetInBeginSection": 969,
"offsetInEndSection": 1234,
"text": "Finally, we found that DC incubation with the drug(s) enhanced IκB expression and that oprozomib inhibited NF-κB expression. We concluded that based on its activity and oral bioavailability, oprozomib merits further investigation in an animal GvHD prevention model.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24103732",
"endSection": "abstract"
},
{
"offsetInBeginSection": 798,
"offsetInEndSection": 1148,
"text": "At clinically relevant concentrations, carfilzomib and oprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. Accordingly, carfilzomib and oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387",
"endSection": "abstract"
},
{
"offsetInBeginSection": 384,
"offsetInEndSection": 698,
"text": "We recently reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770",
"endSection": "abstract"
},
{
"offsetInBeginSection": 354,
"offsetInEndSection": 707,
"text": "Next generation proteasome inhibitors include carfilzomib and oprozomib which are irreversible epoxyketone proteasome inhibitors; and ixazomib and delanzomib which are reversible boronic acid proteasome inhibitors. Two proteasome inhibitors, bortezomib and carfilzomib are FDA approved drugs and ixazomib and oprozomib are in late stage clinical trials.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25935605",
"endSection": "abstract"
}
] |
52b2f3b74003448f5500000c | Is there a relationship between junctin and ryanodine receptors? | Yes, junctin binds to ryanodine receptors within the junctional sarcoplasmic reticulum of calcium release units, and normally acts as an activator of RyR channels at low luminal [Ca(2+)], and as an inhibitor at high luminal [Ca(2+)]. | [
"19230141",
"22025663",
"24257462",
"19448693",
"11162129",
"19398037"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 180,
"text": "Junctin, a 26 kDa intra-sarcoplasmic reticulum (SR) protein, forms a quaternary complex with triadin, calsequestrin and the ryanodine receptor (RyR) at the junctional SR membrane. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22025663",
"endSection": "abstract"
},
{
"offsetInBeginSection": 769,
"offsetInEndSection": 919,
"text": "Junctin ablation appears to affect how RyRs 'sense' SR Ca(2+) load, resulting in decreased diastolic SR Ca(2+) leak despite an elevated [Ca(2+)](SR). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22025663",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1120,
"offsetInEndSection": 1804,
"text": "Single channel recordings of RyRs from WT and JCN-KO cardiac SR indicate that the absence of junctin produces a dual effect on the normally linear response of RyRs to luminal [Ca(2+)]: at low luminal [Ca(2+)] (<1 mmol l(-1)), junctin-devoid RyR channels are less responsive to luminal [Ca(2+)]; conversely, high luminal [Ca(2+)] turns them hypersensitive to this form of channel modulation. Thus, junctin produces complex effects on Ca(2+) sparks, transients, and leak, but the luminal [Ca(2+)]-dependent dual response of junctin-devoid RyRs demonstrates that junctin normally acts as an activator of RyR channels at low luminal [Ca(2+)], and as an inhibitor at high luminal [Ca(2+)].",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22025663",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 287,
"text": "Normal Ca(2+) signalling in skeletal muscle depends on the membrane associated proteins triadin and junctin and their ability to mediate functional interactions between the Ca(2+) binding protein calsequestrin and the type 1 ryanodine receptor in the lumen of the sarcoplasmic reticulum.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19398037",
"endSection": "abstract"
},
{
"offsetInBeginSection": 612,
"offsetInEndSection": 1212,
"text": "We show here that purified skeletal ryanodine receptors are similarly activated by purified triadin or purified junctin added to their luminal side, although a lack of competition indicated that the proteins act at independent sites. Surprisingly, triadin and junctin differed markedly in their ability to transmit information between skeletal calsequestrin and ryanodine receptors. Purified calsequestrin inhibited junctin/triadin-associated, or junctin-associated, ryanodine receptors and the calsequestrin re-associated channel complexes were further inhibited when luminal Ca(2+) fell from 1mM to",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19398037",
"endSection": "abstract"
},
{
"offsetInBeginSection": 604,
"offsetInEndSection": 797,
"text": "By fusing GCaMP6f to the N-terminus of triadin 1 or junctin, GCaMP6f-T/J was targeted to dyadic junctions, where it colocalized with t-tubules and RyRs after adenovirus-mediated gene transfer. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24257462",
"endSection": "abstract"
},
{
"offsetInBeginSection": 180,
"offsetInEndSection": 532,
"text": "The junctional face of the jSR, facing the transverse tubules, is occupied by a molecular complex composed of the transmembrane Ca2+ release channels (ryanodine receptors); the luminal protein calsequestrin (CSQ); the 2 membrane proteins, junctin (Jct), and triadin (Tr), which mediate CSQ-ryanodine receptor interactions; and several other components.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19448693",
"endSection": "abstract"
},
{
"offsetInBeginSection": 161,
"offsetInEndSection": 581,
"text": "Calsequestrin, the main calcium buffer in the sarcoplasmic reticulum, provides a pool of calcium for release through the ryanodine receptor and acts as a luminal calcium sensor for the channel via its interactions with triadin and junctin. We examined the influence of phosphorylation of calsequestrin on its ability to store calcium, to polymerise and to regulate ryanodine receptors by binding to triadin and junctin. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19230141",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 177,
"text": "Junctin is a 26 kDa membrane protein that binds to calsequestrin, triadin, and ryanodine receptors (RyRs) within the junctional sarcoplasmic reticulum of calcium release units. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11162129",
"endSection": "abstract"
}
] |
5149f494d24251bc0500004c | Which medication should be administered when managing patients with suspected acute opioid overdose? | Naloxone is opioid anagonist that should be administered for all patients with suspected acute opioid overdose. Intravenous naltrexone hydrochloride is usually administered, however, other formulations, including enteral methylnaltrexone, nebulized naloxone and subcutaneous naloxone, are under investigation and can be used under certain circumstances. | [
"9562190",
"8907145",
"11015242",
"11130352",
"1470965",
"21044832",
"17849242"
] | factoid | [
{
"offsetInBeginSection": 12,
"offsetInEndSection": 145,
"text": "Opioid overdose has a high mortality, but is often reversible with appropriate overdose management and naloxone (opioid antagonist). ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21044832",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1691,
"offsetInEndSection": 1782,
"text": "Training clinicians how to manage an opioid overdose and administer naloxone was effective.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21044832",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 2841,
"offsetInEndSection": 3085,
"text": "For patients who have ingested dextromethorphan and are sedated or comatose, naloxone, in the usual doses for treatment of opioid overdose, can be considered for prehospital administration, particularly if the patient has respiratory depression",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17849242",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 200,
"offsetInEndSection": 394,
"text": "Naloxone hydrochloride, an injectable opioid antagonist which reverses the respiratory depression, sedation and hypotension associated with opioids, has long been used to treat opioid overdose. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11130352",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 394,
"offsetInEndSection": 567,
"text": "Experts have suggested that, as part of a comprehensive overdose prevention strategy, naloxone should be provided to heroin users for peer administration after an overdose. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11130352",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 184,
"offsetInEndSection": 336,
"text": "Patients who received naloxone for known or presumed opioid overdose were formally evaluated one hour later for multiple potential predictor variables. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11015242",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 741,
"offsetInEndSection": 843,
"text": "Patients with presumed opioid overdose can be safely discharged one hour after naloxone administration",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11015242",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 11,
"offsetInEndSection": 202,
"text": "To determine whether naloxone administered i.v. to out-of-hospital patients with suspected opioid overdose would have a more rapid therapeutic onset than naloxone given subcutaneously (s.q.).",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9562190",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 540,
"offsetInEndSection": 677,
"text": "Subjects received either naloxone 0.4 mg i.v. (n = 74) or naloxone 0.8 mg s.q. (n = 122), for respiratory depression of <10 breaths/min. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9562190",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1143,
"offsetInEndSection": 1371,
"text": "There was no clinical difference in the time interval to respiratory rate > or =10 breaths/min between naloxone 0.8 mg s.q. and naloxone 0.4 mg i.v. for the out-of-hospital management of patients with suspected opioid overdose. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9562190",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 243,
"offsetInEndSection": 518,
"text": "To illustrate this problem, we report the case of a patient inappropriately treated with naloxone and the results of a retrospective review of the medical records of 15 consecutive patients with cancer treated with naloxone in the emergency department over a 5-month period. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8907145",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1150,
"offsetInEndSection": 1360,
"text": "Management of opioid overdose, whether illicit or iatrogenic, requires the prompt and skillful use of opioid overdose, whether illicit or iatrogenic, requires the prompt and skillful use of opioid antagonists. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1470965",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1431,
"offsetInEndSection": 1677,
"text": " The proportion of clinicians willing to use naloxone in an opioid overdose rose from 77% to 99% after training. Barriers to implementing training were clinician time and confidence, service resources, client willingness and naloxone formulation.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21044832",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 243,
"text": "Opioid overdose is rarely the primary cause of altered mental status in cancer patients receiving opioid therapy. The inappropriate administration of naloxone to reverse an abnormal mental status can cause severe withdrawal symptoms and pain. ",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8907145",
"endSection": "sections.0"
}
] |
56c33e5695c1e7cc5b000001 | In which nuclear compartments is heterochromatin located? | This compartment localizes into three main regions: the peripheral heterochromatin, perinucleolar heterochromatin, and pericentromeric heterochromatin. Silencing appears to be associated with histone H3 lysine 9 trimethylation (H3K9me3), DNA methylation and the localization of the silenced gene to a specific nuclear compartment enriched in these modification | [
"23834025",
"16254244",
"12432450",
"22251972",
"20026667",
"19889207",
"21283637",
"15564378"
] | list | [
{
"offsetInBeginSection": 260,
"offsetInEndSection": 410,
"text": "This compartment localizes into three main regions: the peripheral heterochromatin, perinucleolar heterochromatin, and pericentromeric heterochromatin",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23834025",
"endSection": "abstract"
},
{
"offsetInBeginSection": 686,
"offsetInEndSection": 967,
"text": "By separating cells according to transgene expression we show here that silencing appears to be associated with histone H3 lysine 9 trimethylation (H3K9me3), DNA methylation and the localization of the silenced gene to a specific nuclear compartment enriched in these modifications",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19889207",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 197,
"text": "The cell nucleus is divided into chromosome territories and the extrachromosomal domain. The latter includes several structural and functional compartments involved in RNA processing and transport.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12432450",
"endSection": "abstract"
},
{
"offsetInBeginSection": 798,
"offsetInEndSection": 1001,
"text": "We also describe a new apocentric nuclear compartment with a unique set of histone modifications that occurs as a zone of chromatin surrounding centromeric heterochromatin in differentiated lymphocytes. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15564378",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 218,
"text": "Little is known about the mechanisms of gene targeting within the nucleus and its effect on gene expression, but most studies have concluded that genes located near the nuclear periphery are silenced by heterochromatin",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22251972",
"endSection": "abstract"
},
{
"offsetInBeginSection": 894,
"offsetInEndSection": 1129,
"text": "After TSA and NaBt treatment, the HP1 proteins were repositioned more internally in the nucleus, being closely associated with interchromatin compartments, while centromeric heterochromatin was relocated closer to the nuclear periphery",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16254244",
"endSection": "abstract"
},
{
"offsetInBeginSection": 526,
"offsetInEndSection": 850,
"text": "Taking into account the different heterochromatic and euchromatic compartments of the genome, our data suggest that the relative abundance of Ty3/gypsy LTRrs along each chromosome arm is determined mainly by the different proportions of heterochromatin, particularly pericentric heterochromatin, relative to total arm length",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21283637",
"endSection": "abstract"
}
] |
53552ed7f1005d6b58000001 | Have mutations in the ZEB2 gene been found in any human syndrome? | Yes, the Mowat-Wilson syndrome | [
"17958891",
"19842203",
"17203459",
"23523603",
"23243526",
"24029077",
"24282181",
"18445050",
"23427518",
"23322667",
"16053902",
"22486326",
"19215041",
"16688751",
"23001561",
"22246645",
"20428734",
"23152852",
"16150342",
"17932455",
"20093881",
"21893004",
"17223398",
"15908750",
"18259761",
"23312518",
"20125191",
"18230842",
"12746390",
"23466526",
"14681759",
"16088920",
"15006694",
"20145308",
"16532472",
"19236961"
] | yesno | [
{
"offsetInBeginSection": 12,
"offsetInEndSection": 156,
"text": "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24282181",
"endSection": "abstract"
},
{
"offsetInBeginSection": 17,
"offsetInEndSection": 233,
"text": "Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic facial features, a variety of congenital anomalies such as Hirschsprung disease, and intellectual disabilities caused by mutation or deletion of ZEB2 gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24029077",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 111,
"text": "owat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23523603",
"endSection": "abstract"
},
{
"offsetInBeginSection": 290,
"offsetInEndSection": 354,
"text": "MWS is caused by de novo heterozygous mutations in the ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23466526",
"endSection": "abstract"
},
{
"offsetInBeginSection": 219,
"offsetInEndSection": 274,
"text": "The cause of MWS is a de novo mutation in the ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23427518",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 111,
"text": "owat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23322667",
"endSection": "abstract"
},
{
"offsetInBeginSection": 536,
"offsetInEndSection": 691,
"text": "MWS have a heterozygous loss-of-function mutation in the zinc finger E-box protein 2 (ZEB2) gene, also called SIP1 (Smad-interacting protein 1) and ZFHX1B,",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23243526",
"endSection": "abstract"
},
{
"offsetInBeginSection": 856,
"offsetInEndSection": 974,
"text": " human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23152852",
"endSection": "abstract"
},
{
"offsetInBeginSection": 153,
"offsetInEndSection": 215,
"text": "Mutations at the hZeb2 locus cause Mowat-Wilson syndrome (MWS)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23001561",
"endSection": "abstract"
},
{
"offsetInBeginSection": 32,
"offsetInEndSection": 76,
"text": "Mowat-Wilson syndrome and a mutation in ZEB2",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22486326",
"endSection": "title"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 93,
"text": "owat-Wilson syndrome (MWS) is caused by a heterozygous mutation or deletion of the ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22246645",
"endSection": "abstract"
},
{
"offsetInBeginSection": 332,
"offsetInEndSection": 397,
"text": "The syndrome is caused by mutations or deletions of the ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21893004",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 85,
"text": "owat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21893004",
"endSection": "abstract"
},
{
"offsetInBeginSection": 632,
"offsetInEndSection": 710,
"text": "single-copy ZEB2 gene deletion at 2q22.3 consistent with Mowat-Wilson syndrome",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20093881",
"endSection": "abstract"
},
{
"offsetInBeginSection": 206,
"offsetInEndSection": 305,
"text": "Mowat-Wilson syndrome, confirmed by molecular analysis as a heterozygous deletion of the ZEB2 gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20145308",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1006,
"offsetInEndSection": 1084,
"text": "deletion encompassing ZEB2, the gene responsible for the Mowat-Wilson syndrome",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20125191",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1038,
"offsetInEndSection": 1082,
"text": " Six patients had deletions in the ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203",
"endSection": "abstract"
},
{
"offsetInBeginSection": 14,
"offsetInEndSection": 58,
"text": "ZEB2 gene analysis for Mowat-Wilson syndrome",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203",
"endSection": "title"
},
{
"offsetInBeginSection": 1144,
"offsetInEndSection": 1257,
"text": "Mowat-Wilson syndrome (MWS) like appearance was noted. The disease is caused by mutation or deletion of ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19236961",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 127,
"text": "owat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19215041",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 185,
"text": "owat-Wilson syndrome (MWS) is an autosomal dominant developmental disorder with mental retardation and variable multiple congenital abnormalities due to mutations of the ZEB2 (ZFHX1B) ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18445050",
"endSection": "abstract"
},
{
"offsetInBeginSection": 931,
"offsetInEndSection": 1071,
"text": "MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17958891",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 153,
"text": "owat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17932455",
"endSection": "abstract"
},
{
"offsetInBeginSection": 704,
"offsetInEndSection": 778,
"text": "the ZFHX1B gene, which is known to be involved in the Mowat-Wilson syndrom",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17223398",
"endSection": "abstract"
},
{
"offsetInBeginSection": 357,
"offsetInEndSection": 435,
"text": "de novo heterozygous mutations or deletions of the ZFHX1B gene located at 2q22",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17203459",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 113,
"text": "owat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17203459",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 55,
"text": "FHX1B mutations in patients with Mowat-Wilson syndrome",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17203459",
"endSection": "title"
},
{
"offsetInBeginSection": 332,
"offsetInEndSection": 390,
"text": "Mutations leading to haploinsufficiency of the ZFHX1B gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16688751",
"endSection": "abstract"
},
{
"offsetInBeginSection": 11,
"offsetInEndSection": 98,
"text": "mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16688751",
"endSection": "title"
},
{
"offsetInBeginSection": 9,
"offsetInEndSection": 69,
"text": "ZFHX1B mutation associated with a mild Mowat-Wilson syndrome",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16532472",
"endSection": "title"
},
{
"offsetInBeginSection": 20,
"offsetInEndSection": 197,
"text": "Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16150342",
"endSection": "abstract"
},
{
"offsetInBeginSection": 310,
"offsetInEndSection": 441,
"text": "Heterozygous mutations or deletions involving the gene ZFHX1B (previously SIP1) [OMIM 605802] have recently been found to cause MWS",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16088920",
"endSection": "abstract"
},
{
"offsetInBeginSection": 567,
"offsetInEndSection": 680,
"text": " ZFHX1B deletions, splice site or truncating mutations were detected in all 28 patients classified as typical MWS",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16053902",
"endSection": "abstract"
},
{
"offsetInBeginSection": 27,
"offsetInEndSection": 117,
"text": "Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B)",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15908750",
"endSection": "title"
},
{
"offsetInBeginSection": 437,
"offsetInEndSection": 499,
"text": " mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15908750",
"endSection": "abstract"
},
{
"offsetInBeginSection": 38,
"offsetInEndSection": 172,
"text": "ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the \"Mowat-Wilson\" syndrome",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15006694",
"endSection": "title"
},
{
"offsetInBeginSection": 150,
"offsetInEndSection": 287,
"text": " ZFHX1B mutations cause a complex developmental phenotype characterized by severe mental retardation (MR) and multiple congenital defects",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15006694",
"endSection": "abstract"
},
{
"offsetInBeginSection": 11,
"offsetInEndSection": 118,
"text": "mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14681759",
"endSection": "title"
},
{
"offsetInBeginSection": 474,
"offsetInEndSection": 572,
"text": "syndrome is the result of heterozygous deletions or truncating mutations of the ZFHX1B (SIP1) gene",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12746390",
"endSection": "abstract"
},
{
"offsetInBeginSection": 686,
"offsetInEndSection": 737,
"text": "humans with Zfhx1b mutations (Mowat-Wilson syndrome",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23312518",
"endSection": "abstract"
},
{
"offsetInBeginSection": 511,
"offsetInEndSection": 665,
"text": "syndrome occurs as a result of heterozygous mutations or deletions in the zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20428734",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1,
"offsetInEndSection": 72,
"text": "owat-Wilson syndrome (MWS) is a recently delineated mental retardation;",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20428734",
"endSection": "abstract"
},
{
"offsetInBeginSection": 14,
"offsetInEndSection": 126,
"text": "Mowat-Wilson syndrome is a congenital syndrome caused by a defect of the transcriptional repressor ZFHX1B (SIP1)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18259761",
"endSection": "abstract"
},
{
"offsetInBeginSection": 443,
"offsetInEndSection": 537,
"text": "Mowat-Wilson syndrome patients, and all siblings had the same E87X nonsense mutation in ZFHX1B",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18230842",
"endSection": "abstract"
}
] |
5547a7e9f35db75526000006 | Which enzymes are involved in global genome nucleotide excision repair (GG-NER) in bacteria? | Nucleotide excision repair (NER) is universally used to recognize and remove many types of DNA damage. In eubacteria, the NER system typically consists of UvrA, UvrB, UvrC, the UvrD helicase, DNA polymerase I, and ligase. Damage recognition during bacterial NER depends upon UvrA, which binds to the damage and loads UvrB onto the DNA. Subsequently, UvrA, UvrB and UvrC form the excinuclease protein UvrABC endonuclease, a multi-enzymatic complex which carries out repair of damaged DNA in sequential manner. In some cases, Cho may be the effective nuclease for NER, rather than UvrC. UvrC nuclease and the short oligonucleotide that contains the DNA lesion are removed from the post-incision complex by UvrD, a superfamily 1A helicase. In gram-positive organisms, PcrA helicase can also displace UvrC and the excised oligonucleotide from a post-incision NER complex. | [
"20004108",
"19617358",
"19933360",
"24290807",
"23963890",
"23245695",
"21145481",
"19762288",
"22559785",
"25463394"
] | list | [
{
"offsetInBeginSection": 169,
"offsetInEndSection": 455,
"text": "we evaluated the in vivo role of NER in the repair of DNA adducts generated by psoralens (mono- or bi-functional) and UV-A light (PUVA) in E. coli. Cultures of wild-type E. coli K12 and mutants for uvrA, uvrB, uvrC or uvrAC genes were treated with PUVA and cell survival was determined.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20004108",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 221,
"text": "Nucleotide excision repair (NER) is universally used to recognize and remove many types of DNA damage. In eubacteria, the NER system typically consists of UvrA, UvrB, UvrC, the UvrD helicase, DNA polymerase I, and ligase.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19933360",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 207,
"text": "During nucleotide excision repair (NER) in bacteria the UvrC nuclease and the short oligonucleotide that contains the DNA lesion are removed from the post-incision complex by UvrD, a superfamily 1A helicase.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19762288",
"endSection": "abstract"
},
{
"offsetInBeginSection": 349,
"offsetInEndSection": 416,
"text": "UvrD interacts with UvrB, a component of the post-incision complex.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19762288",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1162,
"offsetInEndSection": 1400,
"text": "PcrA helicase from Bacillus stearothermophilus can also displace UvrC and the excised oligonucleotide from a post-incision NER complex, which supports the idea that PcrA performs a UvrD-like function during NER in gram-positive organisms.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19762288",
"endSection": "abstract"
},
{
"offsetInBeginSection": 957,
"offsetInEndSection": 1032,
"text": "Cho rather than UvrC seems to be an effective nuclease for the NER of DPCs.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19617358",
"endSection": "abstract"
},
{
"offsetInBeginSection": 312,
"offsetInEndSection": 478,
"text": "Nucleotide excision repair consists of excinuclease protein UvrABC endonuclease, multi-enzymatic complex which carries out repair of damaged DNA in sequential manner.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23963890",
"endSection": "abstract"
},
{
"offsetInBeginSection": 223,
"offsetInEndSection": 502,
"text": "Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) were submitted to increasing concentrations of cisplatin, and the results revealed that uvrA and uvrB mutants are sensitive to this agent, while uvrC and cho mutants remain as the wild type strain.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23245695",
"endSection": "abstract"
},
{
"offsetInBeginSection": 401,
"offsetInEndSection": 1194,
"text": "we used a genetic approach to investigate the roles of nucleotide excision repair (NER) pathway components in H. pylori mutation and recombination. RESULTS: Inactivation of any of the four uvr genes strongly increased the susceptibility of H. pylori to DNA damage by ultraviolet light. Inactivation of uvrA and uvrB significantly decreased mutation frequencies whereas only the uvrA deficient mutant exhibited a significant decrease of the recombination frequency after natural transformation. A uvrC mutant did not show significant changes in mutation or recombination rates; however, inactivation of uvrC promoted the incorporation of significantly longer fragments of donor DNA (2.2-fold increase) into the recipient chromosome. A deletion of uvrD induced a hyper-recombinational phenotype.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22559785",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 586,
"text": "Transcription-coupled DNA repair (TCR) is a subpathway of nucleotide excision repair (NER) that is triggered when RNA polymerase is stalled by DNA damage. Lesions targeted by TCR are repaired more quickly than lesions repaired by the transcription-independent \"global\" NER pathway, but the mechanism underlying this rate enhancement is not understood. Damage recognition during bacterial NER depends upon UvrA, which binds to the damage and loads UvrB onto the DNA. Bacterial TCR additionally requires the Mfd protein, a DNA translocase that removes the stalled transcription complexes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21145481",
"endSection": "abstract"
}
] |
52b2f1724003448f5500000b | Is JTV519 (K201) a potential drug for the prevention of arrhythmias? | Yes, JTV519 has antiarrhythmic properties. | [
"20581784",
"15584870",
"16825580",
"21291389",
"22001562",
"15073377",
"22563249",
"20080988",
"17644079",
"23144205",
"17994112",
"11090108",
"12890053",
"16672364",
"16185151"
] | yesno | [
{
"offsetInBeginSection": 330,
"offsetInEndSection": 636,
"text": "We compared the suppressive effect of K201 (JTV519), a multiple-channel blocker and cardiac ryanodine receptor-calcium release channel (RyR2) stabilizer, with that of diltiazem, a Ca(2+ )channel blocker, in 2 studies of isoproterenol-induced (n = 30) and ischemic-reperfusion-induced VAs (n = 38) in rats. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23144205",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1055,
"offsetInEndSection": 1584,
"text": "After administration of isoproterenol under Ca(2+) loading, fatal VA frequently occurred in the vehicle (9 of 10 animals, 90%) and diltiazem (8 of 10, 80%) groups, and K201 significantly suppressed the incidences of arrhythmia and mortality (2 of 10, 20%). In the reperfusion study, the incidence and the time until occurrence of reperfusion-induced VA and mortality were significantly suppressed in the K201 (2 of 15 animals, 13%) and diltiazem (1 of 9 animals, 11%) groups compared to the vehicle group (8 of 14 animals, 57%). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23144205",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1707,
"offsetInEndSection": 1860,
"text": "K201 markedly suppressed both the isoproterenol-induced and the reperfusion-induced VAs, whereas diltiazem did not suppress the isoproterenol-induced VA.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23144205",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1614,
"offsetInEndSection": 1876,
"text": "JTV519 (K201) is a newly developed 1,4-benzothiazepine drug with antiarrhythmic and cardioprotective properties. It appears to be very effective in not only preventing but also in reversing the characteristic myocardial changes and preventing lethal arrhythmias.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22563249",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 389,
"text": "The novel antiarrhythmic drug K201 (4-[3-{1-(4-benzyl)piperidinyl}propionyl]-7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine monohydrochloride) is currently in development for treatment of atrial fibrillation. K201 not only controls intracellular calcium release by the ryanodine receptors, but also possesses a ventricular action that might predispose to torsade de pointes arrhythmias. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22001562",
"endSection": "abstract"
},
{
"offsetInBeginSection": 969,
"offsetInEndSection": 1152,
"text": "The RyR is currently used as a therapeutic target in malignant hyperthermia where dantrolene is effective and to relieve ventricular arrhythmia, with the use of JTV519 and flecainide.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21291389",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1200,
"offsetInEndSection": 1372,
"text": "Finally, KN-3 and JTV519, two compounds that stabilize RyR2 in the closed state, prevent the induction of triggered activity and suppress the inducibility of sustained AF. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20581784",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1639,
"offsetInEndSection": 1718,
"text": "JTV-519 greatly reduced the frequency of ouabain-induced arrhythmogenic events.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20080988",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1914,
"offsetInEndSection": 1995,
"text": "Stabilization of RyR2 by JTV-519 effectively reduces these triggered arrhythmias.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20080988",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1473,
"offsetInEndSection": 1537,
"text": "These findings may reveal the anti-arrhythmic potential of K201.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17994112",
"endSection": "abstract"
},
{
"offsetInBeginSection": 225,
"offsetInEndSection": 340,
"text": "The preferential ryanodine receptor stabilizer (K201) possesses antiarrhythmic effects through calcium regulation. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17994112",
"endSection": "abstract"
},
{
"offsetInBeginSection": 11,
"offsetInEndSection": 153,
"text": "The drug K201 (JTV-519) increases inotropy and suppresses arrhythmias in failing hearts, but the effects of K201 on normal hearts is unknown. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17644079",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1510,
"offsetInEndSection": 1616,
"text": "K201 fails to prevent DADs in RyR2(R4496C+/-) myocytes and ventricular arrhythmias in RyR2(R4496C+/-) mice",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16825580",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1071,
"offsetInEndSection": 1198,
"text": "In vivo administration of K201 failed to prevent induction of polymorphic ventricular tachycardia (VT) in RyR2(R4496C+/-) mice.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16825580",
"endSection": "abstract"
},
{
"offsetInBeginSection": 893,
"offsetInEndSection": 1089,
"text": "The 1,4-benzothiazepine JTV519, which increases the binding affinity of calstabin-2 for RyR2, inhibited the diastolic SR Ca2+ leak, monophasic action potential alternans and triggered arrhythmias.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16672364",
"endSection": "abstract"
},
{
"offsetInBeginSection": 499,
"offsetInEndSection": 720,
"text": "In arrhythmias, the calstabin2 stabiliser JTV519 did not prevent arrhythmias in calstabin2-/- mice, but reduced the arrhythmias in calstabin2+/- mice, illustrating the antiarrhythmic potential of stabilising calstablin2. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16185151",
"endSection": "abstract"
},
{
"offsetInBeginSection": 412,
"offsetInEndSection": 652,
"text": "In three models of arrhythmias, the calstabin2 stabiliser JTV519 did not prevent arrhythmias in calstabin2(-/-) mice, but reduced the arrhythmias in calstabin2(+/-) mice, illustrating the antiarrhythmic potential of stabilising calstabin2. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15584870",
"endSection": "abstract"
},
{
"offsetInBeginSection": 456,
"offsetInEndSection": 645,
"text": "A derivative of 1,4-benzothiazepine (JTV519) increased the affinity of calstabin2 for RyR2, which stabilized the closed state of RyR2 and prevented the Ca2+ leak that triggers arrhythmias. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15073377",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1480,
"offsetInEndSection": 1732,
"text": "JTV-519 had significant protective effects on atrial fibrillation in the canine sterile pericarditis model, mainly by increasing effective refractory period, suggesting that it may have potential as a novel antiarrhythmic agent for atrial fibrillation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12890053",
"endSection": "abstract"
},
{
"offsetInBeginSection": 871,
"offsetInEndSection": 1002,
"text": "JTV-519 significantly decreased the mean number of sustained atrial fibrillation episodes (from 4.2 +/- 2.9 to 0 +/- 0, P < 0.01). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12890053",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1652,
"offsetInEndSection": 1851,
"text": "We conclude that JTV-519 can exert antiarrhythmic effects against AF by inhibiting repolarizing K(+) currents. The drug may be useful for the treatment of AF in patients with ischaemic heart disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11090108",
"endSection": "abstract"
}
] |
51718fbc8ed59a060a000010 | What is the mechanism of microRNA deregulation in carcinogenesis? | MicroRNAs (miRNAs) are endogenous non-protein coding single-stranded RNAs (19–25 nucleotides in length) generated from cleavage of larger non-coding RNAs by the ribonuclease III enzyme Dicer. They become part of the RNA-induced silencing complex and negatively regulate gene expression by binding to homologous 3'-UTR region of target protein-coding mRNAs as an imperfect match, causing translational repression or degradation. Approximately one-third of the protein-coding genes are susceptible to miRNA regulation. Accumulating evidence indicates that deregulated miRNA expression is associated with the onset and progression of a number of human cancers. Therefore, cancer-associated miRNAs (CA-miRNAs) could regulate target genes by acting either as "oncogenes" or "tumor suppressor miRNA (TS-miRNAs)". In line with this, numerous cancers (e.g. breast, lung, oesophageal, prostate, pancreatic, gastric and colon cancer) have been classified based on their unique miRNA expression profile. | [
"23087084",
"22293089",
"23209884",
"23509776",
"20221895",
"22303357",
"18700954",
"21860412",
"19912656",
"22408395",
"19440243",
"23071542",
"22912875",
"22898998",
"19721809",
"21799879",
"22583478",
"23074383",
"23064433",
"18040713",
"21559780",
"22303318",
"23293655",
"20842113",
"22417299",
"21931505",
"23276969",
"23016435",
"21971665",
"22126155",
"23431261",
"23158014",
"19521961",
"23250910",
"18927107",
"22392644",
"21903334",
"22666523",
"17700064",
"20716340",
"22056881",
"23251295",
"21811665",
"22312290",
"22194833",
"22384020",
"21102580",
"22469780",
"21712563",
"22938091",
"19712461",
"22616882",
"18442408",
"22666228",
"23175432",
"23024649",
"21962230",
"21029445",
"19664288",
"23391324",
"16854228",
"23407615",
"21461395",
"18036240",
"21418558",
"23125218",
"23554741",
"20925959",
"22548175",
"21284896",
"19638982",
"22968430"
] | summary | [
{
"offsetInBeginSection": 239,
"offsetInEndSection": 537,
"text": "MicroRNAs are a class of small non-coding RNAs that negatively regulate gene expression by interacting with the 3'UTR of protein-coding mRNA. MicroRNAs are implicated in nearly all major biological and cellular events, and recent findings further link microRNA deregulation to human carcinogenesis.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23276969",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 130,
"text": "MiR-657 promotes tumorigenesis in hepatocellular carcinoma by targeting transducin-like enhancer protein 1 through NF-κB pathways.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23175432",
"endSection": "title"
},
{
"offsetInBeginSection": 195,
"offsetInEndSection": 312,
"text": "MicroRNAs (miRNAs), which are small non-coding RNAs, are involved in diverse biological functions and carcinogenesis.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23125218",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 924,
"offsetInEndSection": 1063,
"text": "Moreover, we demonstrated that miR-106b downregulates APC expression by directly targeting the 3'-untranslated region of APC messenger RNA.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23087084",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 287,
"offsetInEndSection": 657,
"text": "Furthermore, miRNAs present a mechanism by which genes with diverse functions on multiple pathways can be simultaneously regulated at the post-transcriptional level. However, little is known about the cancer-related pathways through which cancer-associated miRNAs (CA-miRNAs) regulate these processes representing either positive or negative functions in carcinogenesis.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23064433",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 41,
"offsetInEndSection": 602,
"text": "MicroRNAs, known as small noncoding MiRNAs, 19 to 24 nt in length, are important gene regulators and recognized as key players in carcinogenesis. The mechanism lies in that the MiRNAs can conjugate with their targeted mRNA and then lead to the targeted mRNA degradation or repress their translation. Bioinformatic analysis indicates that each MiRNA can regulate hundreds of gene targets and could serve functionally as \"oncogenes\" or \"tumor suppressor genes\", and therefore regulate multiple cellular processes relevant to carcinogenesis and cancer progression.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23016435",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 106,
"text": "microRNAs (miRs) are endogenous small non-coding RNAs that are aberrantly expressed in various carcinomas.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21971665",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 89,
"offsetInEndSection": 253,
"text": "While deregulated miRNA expression levels have been detected in many tumors, whether miRNA functional impairment is also involved in carcinogenesis remains unknown.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22898998",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 263,
"text": "In the last years, microRNAs (miRNA) have emerged as new molecular players involved in carcinogenesis. Deregulation of miRNAs expression has been shown in different human cancer but the molecular mechanism underlying the alteration of miRNA expression is unknown.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19521961",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 269,
"offsetInEndSection": 730,
"text": "These are microRNAs (miRNAs), a class of noncoding RNAs, 20-23 nucleotides in length, that can up or downregulate gene expression of downstream gene targets (including transcription factors, oncogenes, and tumour suppressor genes) at the post-transcriptional level. Some members of this new class of genes seem to have the potential to act simultaneously either as oncogenes or as tumour suppressor genes depending on the molecular microenvironment of the cell.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21903334",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 144,
"offsetInEndSection": 240,
"text": "MicroRNAs can also be affected by chromosomal alterations and thus contribute to carcinogenesis.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22469780",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 48,
"text": "Regulation of hepatocarcinogenesis by microRNAs.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23276969",
"endSection": "title"
},
{
"offsetInBeginSection": 381,
"offsetInEndSection": 537,
"text": "MicroRNAs are implicated in nearly all major biological and cellular events, and recent findings further link microRNA deregulation to human carcinogenesis.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23276969",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 116,
"text": "miR-106b downregulates adenomatous polyposis coli and promotes cell proliferation in human hepatocellular carcinoma.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23087084",
"endSection": "title"
},
{
"offsetInBeginSection": 453,
"offsetInEndSection": 657,
"text": "However, little is known about the cancer-related pathways through which cancer-associated miRNAs (CA-miRNAs) regulate these processes representing either positive or negative functions in carcinogenesis.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23064433",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1406,
"offsetInEndSection": 1681,
"text": "Combined with previous cancer studies, the analysis of the relevance between functions of CA-miRNAs and cancer-related pathways exploring different internal carcinogenesis stimuli also revealed the potential of the top five pathways to regulate core carcinogenesis processes.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23064433",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 41,
"offsetInEndSection": 186,
"text": "MicroRNAs, known as small noncoding MiRNAs, 19 to 24 nt in length, are important gene regulators and recognized as key players in carcinogenesis.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23016435",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 141,
"text": "Androgen pathway stimulates microRNA-216a transcription to suppress the tumor suppressor in lung cancer-1 gene in early hepatocarcinogenesis.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22392644",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 177,
"text": "Deregulation of microRNAs (miRNAs) is common in advanced human hepatocellular carcinoma (HCC); however, the ones involved in early carcinogenesis have not yet been investigated.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22392644",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 116,
"text": "MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22056881",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 236,
"text": "MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22056881",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 96,
"text": "Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to tumorigenesis.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23175432",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 189,
"text": "UNLABELLED: Deregulation of microRNAs (miRNAs) is common in advanced human hepatocellular carcinoma (HCC); however, the ones involved in early carcinogenesis have not yet been investigated.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22392644",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 103,
"offsetInEndSection": 263,
"text": "Deregulation of miRNAs expression has been shown in different human cancer but the molecular mechanism underlying the alteration of miRNA expression is unknown.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19521961",
"endSection": "sections.0"
}
] |
56cdf3e55795f9a73e00003c | Which type of GTPases is required for amino acid-dependent activation of mTORC1? | Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome | [
"24698685",
"25263562",
"24081491",
"22424946",
"24337580",
"24095279",
"25567907",
"25567906",
"23863162",
"25936802",
"21981924"
] | factoid | [
{
"offsetInBeginSection": 108,
"offsetInEndSection": 204,
"text": "Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25936802",
"endSection": "abstract"
},
{
"offsetInBeginSection": 145,
"offsetInEndSection": 344,
"text": "Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25567906",
"endSection": "abstract"
},
{
"offsetInBeginSection": 237,
"offsetInEndSection": 661,
"text": "mTORC1 promotes growth in response to the availability of nutrients, such as amino acids, which drive mTORC1 to the lysosomal surface, its site of activation. How amino acid levels are communicated to mTORC1 is only recently coming to light by the discovery of a lysosome-based signaling system composed of Rags (Ras-related GTPases) and Ragulator v-ATPase, GATOR (GAP activity towards Rags), and folliculin (FLCN) complexes",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24698685",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 353,
"text": "The mechanistic target of rapamycin complex 1 (mTORC1) kinase is a major regulator of cell growth that responds to numerous environmental cues. A key input is amino acids, which act through the heterodimeric Rag GTPases (RagA or RagB bound to RagC or RagD) in order to promote the translocation of mTORC1 to the lysosomal surface, its site of activation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25263562",
"endSection": "abstract"
},
{
"offsetInBeginSection": 497,
"offsetInEndSection": 635,
"text": "The heterodimeric Rag GTPases localize mTORC1 to lysosomes by their amino-acid-dependent interaction with the lysosomal Ragulator complex.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23863162",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1070,
"offsetInEndSection": 1274,
"text": "These new findings define the lysosome as a site of action for FLCN and indicate a critical role for FLCN in the amino acid-dependent activation of mTOR via its direct interaction with the RagA/B GTPases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24081491",
"endSection": "abstract"
},
{
"offsetInBeginSection": 847,
"offsetInEndSection": 1061,
"text": "We show that LRS directly binds to Rag GTPase, the mediator of amino acid signaling to mTORC1, in an amino acid-dependent manner and functions as a GTPase-activating protein (GAP) for Rag GTPase to activate mTORC1.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22424946",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 262,
"text": "Activation of mammalian target of rapamycin complex 1 (mTORC1) by amino acids is mediated in part by the Rag GTPases, which bind the raptor subunit of mTORC1 in an amino acid-stimulated manner and promote mTORC1 interaction with Rheb-GTP, the immediate activator",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24337580",
"endSection": "abstract"
},
{
"offsetInBeginSection": 111,
"offsetInEndSection": 271,
"text": "The Rag GTPases interact with mTORC1 and signal amino acid sufficiency by promoting the translocation of mTORC1 to the lysosomal surface, its site of activation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24095279",
"endSection": "abstract"
},
{
"offsetInBeginSection": 138,
"offsetInEndSection": 364,
"text": "Amino acids stimulate mTORC1 activation at the lysosome in a manner thought to be dependent on the Rag small guanosine triphosphatases (GTPases), the Ragulator complex, and the vacuolar H(+)-adenosine triphosphatase (v-ATPase)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25567907",
"endSection": "abstract"
},
{
"offsetInBeginSection": 108,
"offsetInEndSection": 206,
"text": "Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25936802",
"endSection": "abstract"
},
{
"offsetInBeginSection": 145,
"offsetInEndSection": 346,
"text": "Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25567906",
"endSection": "abstract"
},
{
"offsetInBeginSection": 871,
"offsetInEndSection": 1075,
"text": "These new findings define the lysosome as a site of action for FLCN and indicate a critical role for FLCN in the amino acid-dependent activation of mTOR via its direct interaction with the RagA/B GTPases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24081491",
"endSection": "abstract"
},
{
"offsetInBeginSection": 566,
"offsetInEndSection": 801,
"text": "Interestingly, p62 colocalizes with Rags at the lysosomal compartment and is required for the interaction of mTOR with Rag GTPases in vivo and for translocation of the mTORC1 complex to the lysosome, a crucial step for mTOR activation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21981924",
"endSection": "abstract"
},
{
"offsetInBeginSection": 458,
"offsetInEndSection": 595,
"text": "Our results indicate that FLCN is specifically required for the amino acid-stimulated recruitment of mTORC1 to lysosomes by Rag GTPases. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24081491",
"endSection": "abstract"
},
{
"offsetInBeginSection": 493,
"offsetInEndSection": 852,
"text": "Mutation of LRS amino acid residues important for leucine binding renders the mTORC1 pathway insensitive to intracellular levels of amino acids. We show that LRS directly binds to Rag GTPase, the mediator of amino acid signaling to mTORC1, in an amino acid-dependent manner and functions as a GTPase-activating protein (GAP) for Rag GTPase to activate mTORC1.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22424946",
"endSection": "abstract"
}
] |
570921e4cf1c325851000017 | In which genomic regions are Alu enriched? | There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome. Alu elements are more clustered in genes which are involved in metabolism, transport, and signaling processes. In contrast, they are significantly fewer in genes coding for information pathway components as well as structural proteins.
This bias in Alu distribution is independent of the effect of Alu density of the flanking genomic region and is also not affected by the GC content of the gene and its upstream and downstream regions. | [
"2716062",
"12777511",
"6165649",
"23420552",
"12832639",
"11884141"
] | list | [
{
"offsetInBeginSection": 121,
"offsetInEndSection": 317,
"text": "There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639",
"endSection": "abstract"
},
{
"offsetInBeginSection": 427,
"offsetInEndSection": 664,
"text": "These elements are more clustered in genes which are involved in metabolism, transport, and signaling processes. In contrast, they are significantly fewer in genes coding for information pathway components as well as structural proteins.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639",
"endSection": "abstract"
},
{
"offsetInBeginSection": 665,
"offsetInEndSection": 865,
"text": "This bias in Alu distribution is independent of the effect of Alu density of the flanking genomic region and is also not affected by the GC content of the gene and its upstream and downstream regions.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639",
"endSection": "abstract"
},
{
"offsetInBeginSection": 866,
"offsetInEndSection": 1078,
"text": "The relative proportions of Alu subfamilies (Alu J, Alu S, and Alu Y) are not significantly different in genes with high Alu density belonging to the functional categories of transport, metabolism, and signaling.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1199,
"offsetInEndSection": 1332,
"text": "We suggest that Alu elements might be involved in regulatory mechanisms and are therefore differentially selected in primate genomes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639",
"endSection": "abstract"
},
{
"offsetInBeginSection": 449,
"offsetInEndSection": 666,
"text": "Sequence analysis demonstrated these \"young\" Alu insertions represented gene conversion events of pre-existing ancient Alu elements or independent parallel insertions of older Alu elements in the same genomic region. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11884141",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1049,
"offsetInEndSection": 1171,
"text": "This study suggests that the majority of Alu insertions in primate genomes are the products of unique evolutionary events.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11884141",
"endSection": "abstract"
},
{
"offsetInBeginSection": 577,
"offsetInEndSection": 745,
"text": "Our screening of the Alu insertion loci also resulted in the recovery of several \"young\" Alu elements that resided at orthologous positions in nonhuman primate genomes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12777511",
"endSection": "abstract"
}
] |
54df695b1388e8454a000004 | What is the synonym of the lubag disease? | Lubag disease is also known as X-linked dystonia-parkinsonism (XDP). This disease is characterized by dystonia and parkinsonism, and afflicts Filipino men, and rarely, women originating principally from the Panay Island. | [
"12465067",
"12471465",
"1672807",
"21047175",
"23614923",
"18609312",
"17579361",
"8041372",
"15390042",
"25004170",
"8351010",
"8341310",
"8338342",
"15465396",
"20694531",
"23184149",
"15596620",
"16242937"
] | factoid | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 183,
"text": "IMPORTANCE: Despite recessive inheritance, X-linked dystonia-parkinsonism (Lubag disease) has also been described in women presenting with a late-onset isolated parkinsonian syndrome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25004170",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 101,
"text": "Anesthesia for deep brain stimulation in a patient with X-linked dystonia-parkinsonism/Lubag disease.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23614923",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 92,
"text": "Lubag disease is a genetic X-linked dystonia-parkinsonism syndrome afflicting Filipino men. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23614923",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 166,
"text": "X-linked dystonia parkinsonism syndrome (XDP, lubag): disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23184149",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 145,
"text": "X-chromosomal dystonia parkinsonism syndrome (XDP, 'lubag') is associated with sequence changes within the TAF1/DYT3 multiple transcript system. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23184149",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 82,
"text": "The unique phenomenology of sex-linked dystonia parkinsonism (XDP, DYT3, \"Lubag\").",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21047175",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 179,
"text": "Sex-linked dystonia parkinsonism (XDP, DYT3, \"Lubag\") is an adult-onset, progressive, debilitating movement disorder first described in Filipino males from Panay Islands in 1975. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21047175",
"endSection": "abstract"
},
{
"offsetInBeginSection": 294,
"offsetInEndSection": 992,
"text": "We cover dopa-responsive dystonia, Wilson's disease, Parkin-, PINK1-, and DJ-1-associated parkinsonism (PARK2, 6, and 7), x-linked dystonia-parkinsonism/Lubag (DYT3), rapid-onset dystonia-parkinsonism (DYT12) and DYT16 dystonia, the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) including pantothenate kinase (PANK2)- and PLA2G6 (PARK14)-associated neurodegeneration, neuroferritinopathy, Kufor-Rakeb disease (PARK9) and the recently described SENDA syndrome; FBXO7-associated neurodegeneration (PARK15), autosomal-recessive spastic paraplegia with a thin corpus callosum (SPG11), and dystonia parkinsonism due to mutations in the SLC6A3 gene encoding the dopamine transporter.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20694531",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 119,
"text": "Neuropsychological profile of a Filipino gentleman with X-linked dystonia-parkinsonism: a case report of Lubag disease.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18609312",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 141,
"text": "X-Linked Dystonia-Parkinsonism (XDP or \"Lubag\") is a progressive neurodegenerative disorder unique to the Island of Panay in the Philippines.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18609312",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 115,
"text": "First case of X-linked dystonia-parkinsonism (\"Lubag\") to demonstrate a response to bilateral pallidal stimulation.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17579361",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 94,
"text": "\"Lubag\" or X-linked dystonia-parkinsonism (XDP) is a genetic syndrome afflicting Filipino men.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17579361",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 82,
"text": "First case report of X linked dystonia parkinsonism (XDP) or 'lubag' in Australia.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16242937",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "PURPOSE: To present the first genetically supported case of X linked dystonia parkinsonism (XDP) or 'lubag' reported in an Australian hospital. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16242937",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 87,
"text": "Phenotypic and molecular analyses of X-linked dystonia-parkinsonism (\"lubag\") in women.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15596620",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 141,
"text": "BACKGROUND: X-linked dystonia-parkinsonism (XDP) or \"lubag\" is an X-linked recessive disorder that afflicts Filipino men, and rarely, women. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15596620",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Smell testing is abnormal in 'lubag' or X-linked dystonia-parkinsonism: a pilot study.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15465396",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 303,
"text": "We administered a culturally corrected University of Pennsylvania Smell Identification Test (ccUPSIT) consisting of 25 odor items to 20 patients with 'Lubag' or X-linked dystonia-parkinsonism and 20 control subjects matched by sex, age, educational background, smoking history, and geographical origin. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15465396",
"endSection": "abstract"
},
{
"offsetInBeginSection": 321,
"offsetInEndSection": 458,
"text": "Three affected siblings were found to share an identical haplotype at the X-linked dystonia-parkinsonism locus (XDP; Lubag; OMIM*314250).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15390042",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1053,
"offsetInEndSection": 1216,
"text": "These neuropathological findings differed from those of Parkinson's disease or juvenile parkinsonism, but mimic to those of X-linked dystonia parkinsonism (Lubag).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12471465",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 59,
"text": "Phenomenology of \"Lubag\" or X-linked dystonia-parkinsonism.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12465067",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 211,
"text": "X-linked dystonia-parkinsonism (XDP), or Lubag syndrome, is known to cause progressive dystonia, with or without parkinsonism, among Filipino male adults with maternal roots from the Philippine island of Panay. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12465067",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 104,
"text": "Adductor laryngeal breathing dystonia in a patient with lubag (X-linked dystonia-Parkinsonism syndrome).",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8041372",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 154,
"text": "We report a patient with Lubag (X-linked dystonia-parkinsonism) who presented with severe respiratory stridor from adductor laryngeal breathing dystonia. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8041372",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 77,
"text": "Phenotypic expression of X-linked dystonia-parkinsonism (lubag) in two women.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8351010",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 159,
"text": "Lubag (X-linked dystonia-parkinsonism) has been considered a sex-linked recessive trait and has been mapped to the pericentromeric region of the X chromosome. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8351010",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 212,
"text": "Regional and global metabolic rates for glucose (rCMRGlc and GMR) were estimated using [18F]fluorodeoxyglucose and positron emission tomography in 3 patients with Filipino X-linked dystonia-parkinsonism (lubag). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8338342",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 57,
"text": "Neuropathology of lubag (x-linked dystonia parkinsonism).",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8341310",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 125,
"text": "Lubag is an x-linked recessive dystonia parkinsonism that affects Filipino men originating principally from the Panay Island.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8341310",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 132,
"text": "Genetic mapping of \"Lubag\" (X-linked dystonia-parkinsonism) in a Filipino kindred to the pericentromeric region of the X chromosome.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1672807",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 167,
"text": "\"Lubag\" is an X-linked disorder causing dystonia and parkinsonism that has only been described in families from the Philippines, principally from the island of Panay. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1672807",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 139,
"text": "X-Linked Dystonia-Parkinsonism (XDP or \"Lubag\") is a progressive neurodegenerative disorder unique to the Island of Panay in the Philippines",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18609312",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 90,
"text": "Lubag disease is a genetic X-linked dystonia-parkinsonism syndrome afflicting Filipino men",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23614923",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1053,
"offsetInEndSection": 1215,
"text": "These neuropathological findings differed from those of Parkinson's disease or juvenile parkinsonism, but mimic to those of X-linked dystonia parkinsonism (Lubag)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12471465",
"endSection": "abstract"
}
] |
56bcdf1ad36b5da378000009 | Dracorhodin perchlorate was tested for treatment of which cancers? | Dracorhodin perchlorate induce apoptosis in prostate cancer, gastric tumor, melanoma and premyelocytic leukemia. | [
"23869191",
"15215653",
"16864444",
"22711363",
"15684474",
"21505988"
] | list | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 99,
"text": "Dracorhodin perchlorate induced human breast cancer MCF-7 apoptosis through mitochondrial pathways.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191",
"endSection": "title"
},
{
"offsetInBeginSection": 123,
"offsetInEndSection": 317,
"text": "It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1550,
"offsetInEndSection": 1675,
"text": "CONCLUSION: Therefore DP was a candidate for anti-breast cancer, DP induced apoptosis of MCF-7 through mitochondrial pathway.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 196,
"text": "Dracorhodin perchlorate has been recently shown to induce apoptotic cell death in cancer cells. However, the molecular mechanisms underlying these effects are unknown in human gastric tumor cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22711363",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 111,
"text": "Dracorhodin perchlorate suppresses proliferation and induces apoptosis in human prostate cancer cell line PC-3.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21505988",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 130,
"text": "The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21505988",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 134,
"text": "Dracorhodin perchlorate, an anthocyanin red pigment, induces human premyelocytic leukemia HL-60 cell death through apoptotic pathway. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16864444",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 126,
"text": "Dracorhodin perchlorate, an anthocyanin red pigment, induces human melanoma A375-S2 cell death through the apoptotic pathway. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15684474",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 77,
"text": "Dracorhodin perchlorate inhibited proliferation of several tumor cell lines. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15215653",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 129,
"text": "The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21505988",
"endSection": "abstract"
},
{
"offsetInBeginSection": 123,
"offsetInEndSection": 318,
"text": "It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 307,
"text": " Dracorhodin perchlorate (DP) was a synthetic analogue of the antimicrobial anthocyanin red pigment dracorhodin. It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 266,
"text": " The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. After administration of 10-80 μmol/L dracorhodin perchlorate for 12-48 h, cell viability of PC-3 cells was measured by MTT colorimetry.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21505988",
"endSection": "abstract"
},
{
"offsetInBeginSection": 113,
"offsetInEndSection": 401,
"text": "It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated. This study would investigate whether DP was a candidate chemical of anti-human breast cancer.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 307,
"text": "Dracorhodin perchlorate (DP) was a synthetic analogue of the antimicrobial anthocyanin red pigment dracorhodin. It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 266,
"text": "The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. After administration of 10-80 μmol/L dracorhodin perchlorate for 12-48 h, cell viability of PC-3 cells was measured by MTT colorimetry.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21505988",
"endSection": "abstract"
}
] |
550331abe9bde69634000037 | What is the role of venous angioplasty in multiple sclerosis? | Chronic cerebrospinal venous insufficiency (CCSVI) may be an important factor in the pathogenesis of multiple sclerosis (MS). The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain, thereby alleviating some of the symptoms of MS. There have been reports to suggest that venous angioplasty in MS patients is a feasible and safe procedure and is associated with improved disease symptom severity, quality of life, and corrects blood pressure deviation, improves CSF dynamics. Open venous reconstruction of the internal jugular vein has also been tried with good results.
However, some authors have failed to document beneficial value of venous angioplasty in MS patients and systematic review has suggested that there is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS. | [
"22687168",
"21059535",
"23563645",
"21803799",
"21487978",
"21856578",
"22496109",
"22088659",
"22311713",
"23301864",
"21679067",
"20351673",
"22577160",
"23202144",
"20351675",
"22640501",
"23701076",
"23493652",
"23660636",
"23523158",
"21839654",
"23809937",
"23948669",
"23235683",
"22648477",
"21876515",
"22569567",
"23034121",
"22987234",
"20373339",
"23249660",
"22951366",
"24255092",
"23419569",
"21106999",
"23953830",
"24975855",
"23781006",
"19958985",
"23402260",
"21107001",
"21808631",
"22155803",
"23691321",
"23443168"
] | summary | [
{
"offsetInBeginSection": 1850,
"offsetInEndSection": 1977,
"text": "Balloon angioplasty corrects blood pressure deviation in multiple sclerosis patients undergoing internal jugular vein dilation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24255092",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 325,
"text": "PURPOSE: To investigate prevalence of extracranial abnormalities in azygos and internal jugular (IJ) veins using conventional venography and intravascular ultrasound (IVUS) in patients with multiple sclerosis (MS) being evaluated for chronic cerebrospinal venous insufficiency, a condition of vascular hemodynamic dysfunction",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23953830",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 132,
"text": "Feasibility and safety of endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23948669",
"endSection": "title"
},
{
"offsetInBeginSection": 2026,
"offsetInEndSection": 2099,
"text": "CONCLUSIONS: Endovascular treatment for CCSVI appears feasible and safe. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23948669",
"endSection": "abstract"
},
{
"offsetInBeginSection": 204,
"offsetInEndSection": 433,
"text": "This report presents the case of a 45-year-old man with known MS and suspected CCSVI who had undergone previous internal jugular angioplasty and stenting. The patient reported dramatic improvement of symptoms after intervention. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23809937",
"endSection": "abstract"
},
{
"offsetInBeginSection": 565,
"offsetInEndSection": 851,
"text": "Open venous reconstruction of the internal jugular vein was performed with a spiral graft from the saphenous vein. The patient's symptoms improved for several weeks until the venous reconstruction occluded. This case is the first reported open venous reconstruction for suspected CCSVI.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23809937",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 175,
"text": "Percutaneous transluminal angioplasty for treatment of chronic cerebrospinal venous insufficiency in people with multiple sclerosis: a summary of a Cochrane systematic review.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23781006",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 398,
"text": "BACKGROUND: It has been recently hypothesised that chronic cerebrospinal venous insufficiency (CCSVI) may be an important factor in the pathogenesis of multiple sclerosis (MS). The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain, thereby alleviating some of the symptoms of MS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23781006",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1081,
"offsetInEndSection": 1262,
"text": "CONCLUSIONS: There is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23781006",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1813,
"offsetInEndSection": 2019,
"text": "CONCLUSION: The results of the current study suggest that endovascular evaluation and management of chronic cerebrospinal venous insufficiency is safe, with low morbidity and no procedure-related mortality.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23701076",
"endSection": "abstract"
},
{
"offsetInBeginSection": 819,
"offsetInEndSection": 945,
"text": "There are clinical trials ongoing or planned to treat chronic cerebrospinal venous insufficiency (CCSVI) through angioplasty. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23691321",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 166,
"text": "Percutaneous transluminal angioplasty for chronic cerebrospinal venous insufficiency in multiple sclerosis: dichotomy between subjective and objective outcome scores.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23660636",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 234,
"text": "Some multiple sclerosis (MS) patients reported an improvement after percutaneous transluminal angioplasty (PTA) for chronic cerebrospinal venous insufficiency (CCSVI), despite the lack of correspondence with objective outcome scores. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23660636",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1141,
"offsetInEndSection": 1300,
"text": " Spontaneously performed approach to CCSVI does not improve clinical and MRI parameters, despite frequent subjective perception of quality of life improvement.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23660636",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 174,
"text": "Percutaneous angioplasty of internal jugular and azygous veins in patients with chronic cerebrospinal venous insufficiency and multiple sclerosis: early and mid-term results.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23563645",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 151,
"text": "Purpose: To assess the safety of endovascular treatment of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23563645",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1341,
"offsetInEndSection": 1831,
"text": ".Conclusion: Endovascular treatment of the IJV and azygous veins in patients with CCSVI and MS is a safe procedure with no post-procedural complications followed by significant improvement of IJV flow haemodynamic parameters and decrease in the EDSS score. Whether CCSVI percutaneous treatment might affect clinical improvement in patients suffering from MS is yet to be seen after completion of major multicentric clinical trials, still it seems like that this procedure is not negligible.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23563645",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1654,
"offsetInEndSection": 1810,
"text": " CONCLUSIONS: PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23523158",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 288,
"text": "BACKGROUND: It has been postulated that Multiple sclerosis (MS) stems from a narrowing in the veins that drain blood from the brain, known medically as chronic cerebrospinal venous insufficiency, or CCSVI. It has been proposed that balloon angioplasty should alleviate the symptoms of MS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23493652",
"endSection": "abstract"
},
{
"offsetInBeginSection": 517,
"offsetInEndSection": 688,
"text": " The revival of this concept has generated major interest in media and patient groups, mainly driven by the hope that endovascular treatment of 'CCSVI' could alleviate MS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23443168",
"endSection": "abstract"
},
{
"offsetInBeginSection": 822,
"offsetInEndSection": 1022,
"text": " The data obtained here do generally not support the 'CCSVI' concept. Moreover, there are no methodologically adequate studies to prove or disprove beneficial effects of endovascular treatment in MS. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23443168",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 230,
"text": "RATIONALE: It is estimated that some hundreds of Canadian patients with multiple sclerosis (MS) have journeyed abroad to avail themselves of 'liberation therapy' (venoplasty) following the initial report by Zamboni et al in 2009. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23419569",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1235,
"offsetInEndSection": 1400,
"text": "CONCLUSION: No objective improvement was found at one year in thirty MS subjects who had undergone venoplasty, although many reported a degree of subjective benefit.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23419569",
"endSection": "abstract"
},
{
"offsetInBeginSection": 128,
"offsetInEndSection": 274,
"text": "Zamboni et al. reported significant improvement in neurological outcomes in MS patients who underwent percutaneous transluminal angioplasty (PTA).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23301864",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1515,
"offsetInEndSection": 1733,
"text": "CONCLUSION: The study revealed that PTA in relapsing remitting MS patients was not associated with any neurological improvement. However, there was an increase in disease activity irrespective of the adherence to DMTs.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23301864",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 161,
"text": "Serious complication of percutaneous angioplasty with stent implantation in so called \"chronic cerebrospinal venous insufficiency\" in multiple sclerosis patient.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23249660",
"endSection": "title"
},
{
"offsetInBeginSection": 943,
"offsetInEndSection": 1082,
"text": "We strongly ask for restriction of PTA procedure in so called CCSVI, which concept was not proven to be relevant to MS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23249660",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 137,
"text": "Percutaneous transluminal angioplasty for treatment of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis patients.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23235683",
"endSection": "title"
},
{
"offsetInBeginSection": 682,
"offsetInEndSection": 903,
"text": "The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain thereby alleviating some of the symptoms of MS. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23235683",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2031,
"offsetInEndSection": 2222,
"text": "AUTHORS' CONCLUSIONS: There is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23235683",
"endSection": "abstract"
},
{
"offsetInBeginSection": 692,
"offsetInEndSection": 796,
"text": "Significant improvement of clinical disability in relapsing-remitting patients was (P < 0.001) achieved.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23202144",
"endSection": "abstract"
},
{
"offsetInBeginSection": 465,
"offsetInEndSection": 647,
"text": "Data from a few small case series suggest possible improvement of the clinical course and quality of life by performing percutaneous balloon angioplasty (PTA) of the stenotic veins. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23034121",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1275,
"offsetInEndSection": 1422,
"text": "CONCLUSION: In the case presented, PTA of the IJV confluence resulted in haemodynamic improvement despite the presence of IJV external compression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22987234",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1543,
"offsetInEndSection": 1685,
"text": "CONCLUSIONS: Endovascular treatment of CCSVI in patients with MS appears to be a safe procedure resulting in significant clinical improvement.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22951366",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1728,
"offsetInEndSection": 1905,
"text": "Endovascular treatment of concurrent CCSVI seems to be safe and repeatable and may reduce annual relapse rates and cumulative disability in patients with relapsing-remitting MS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22687168",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1355,
"offsetInEndSection": 1495,
"text": "Therefore, any potentially harmful interventional treatment such as transluminal angioplasty and/or stenting should be strongly discouraged.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22648477",
"endSection": "abstract"
},
{
"offsetInBeginSection": 898,
"offsetInEndSection": 1173,
"text": "The work of Dr. Zamboni, et al, who reported that treating the venous stenoses causing CCSVI with angioplasty resulting in significant improvement in the symptoms and quality of life of patients with MS (2) has led to further interest in this theory and potential treatment. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22640501",
"endSection": "abstract"
},
{
"offsetInBeginSection": 237,
"offsetInEndSection": 493,
"text": "Regardless of this continued uncertainty surrounding the safety and efficacy of this therapy, MS patients from Canada, and other jurisdictions, are traveling abroad to receive central venous angioplasty and, unfortunately, some also receive venous stents. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22577160",
"endSection": "abstract"
},
{
"offsetInBeginSection": 898,
"offsetInEndSection": 1150,
"text": "Finally, no proven (i.e., based on strict scientific methodology and on the rules of evidence-based medicine) therapeutic effect of the \"liberation\" procedure (unblocking the extracranial venous obstruction using angioplasty) has been shown up to date.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22569567",
"endSection": "abstract"
},
{
"offsetInBeginSection": 759,
"offsetInEndSection": 957,
"text": "The angiographic and hemodynamic improvement was associated with improvement in symptomatology, most particularly in cognitive and constitutional symptoms that may be related to cerebrovenous flow. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22496109",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1072,
"offsetInEndSection": 1287,
"text": " In conclusion, in this series, endovascular intervention to correct venous stenosis associated with multiple sclerosis was associated with improvement in symptoms possibly related to disturbed venous hemodynamics. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22496109",
"endSection": "abstract"
},
{
"offsetInBeginSection": 932,
"offsetInEndSection": 1385,
"text": "Some investigators have proceeded to unblinded nonrandomized angioplasty and stenting procedures in patients with CCSVI, with anecdotal reports of symptom improvement. Because of conflicting data on the presence of CCSVI and the absence of controlled trials of CCSVI intervention, the current standard of clinical care is neither to evaluate multiple sclerosis (MS) patients for CCSVI anomalies, nor to intervene with procedures to alter such anomalies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22311713",
"endSection": "abstract"
},
{
"offsetInBeginSection": 478,
"offsetInEndSection": 640,
"text": "Endovascular treatment (percutaneous transluminal angioplasty (PTA) with or without stenting) of CCSVI was reported to be feasible with a minor complication rate.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22155803",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1180,
"offsetInEndSection": 1363,
"text": "PTA seems to be an effective treatment for patients with CCVI and multiple sclerosis, However, randomized studies are warranted to establish the efficacy of this new treatment for MS.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22155803",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1577,
"offsetInEndSection": 1687,
"text": "CONCLUSIONS: Endovascular treatment of CCSVI is a safe procedure; there is a 1.6% risk of major complications.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22088659",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1589,
"offsetInEndSection": 1837,
"text": "CONCLUSIONS: The endovascular treatment in patients with MS and concomitant CCSVI did not have an influence on the patient's neurological condition; however, in the mid-term follow-up, an improvement in some quality-of-life parameters was observed.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21876515",
"endSection": "abstract"
},
{
"offsetInBeginSection": 338,
"offsetInEndSection": 678,
"text": "Although there is no methodologically rigorous evidence to support this hypothesis presently, a considerable number of MS patients have undergone endovascular CCSVI procedures. Such procedures include angioplasty or stent placement in jugular and azygous veins. The safety and efficacy of these procedures is unknown, but not without risk. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21856578",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1148,
"offsetInEndSection": 1352,
"text": "CONCLUSIONS: As the debate about CCSVI and its relationship to MS continues, the complications and risks associated with venous stenting and angioplasty in jugular and azygous veins are becoming clearer. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21856578",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1246,
"offsetInEndSection": 1358,
"text": "CONCLUSIONS: This study further confirms the safety of PTA treatment in patients with CCSVI associated with MS. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21839654",
"endSection": "abstract"
},
{
"offsetInBeginSection": 336,
"offsetInEndSection": 581,
"text": "This review aims to describe the proposed association between CCSVI and MS, summarize the current data, and discuss the role of endovascular therapy and the need for rigorous randomized clinical trials to evaluate this association and treatment.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21808631",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1451,
"offsetInEndSection": 1544,
"text": "CONCLUSION: Endovascular therapy appears to be a safe and reliable method for treating CCSVI.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21679067",
"endSection": "abstract"
},
{
"offsetInBeginSection": 800,
"offsetInEndSection": 999,
"text": "In particular, the potential shift in treatment concepts possibly leading to an interventional treatment approach including balloon angioplasty and venous stent placement is currently being debated. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21487978",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1494,
"offsetInEndSection": 1688,
"text": "In conclusion, the present conclusive data confuting the theory of CCSVI in MS should lead to reluctance with respect to the interventional treatment of possible venous anomalies in MS patients.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21487978",
"endSection": "abstract"
},
{
"offsetInBeginSection": 141,
"offsetInEndSection": 315,
"text": "Although balloon angioplasty and stenting seem to be safe procedures, there are currently no data on the treatment of a large group of patients with this vascular pathology. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21107001",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1315,
"offsetInEndSection": 1564,
"text": "CONCLUSIONS: The procedures appeared to be safe and well tolerated by the patients, regardless of the actual impact of the endovascular treatments for venous pathology on the clinical course of multiple sclerosis, which warrants long-term follow-up.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21107001",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1185,
"offsetInEndSection": 1408,
"text": "Two pilot studies demonstrated the safety and feasibility in Day Surgery of the endovascular treatment of CCSVI by means of balloon angioplasty (PTA). It determines a significant reduction of postoperative venous pressure. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21106999",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1486,
"offsetInEndSection": 1625,
"text": "However, PTA seems to positively influence clinical and QoL parameters of the associated MS and warrants further randomized control trials.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21106999",
"endSection": "abstract"
},
{
"offsetInBeginSection": 520,
"offsetInEndSection": 700,
"text": "Furthermore, they have obtained apparent clinical improvement or stabilization by endovascular ballooning of points of obstruction in the great veins in some, at least temporarily.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21059535",
"endSection": "abstract"
},
{
"offsetInBeginSection": 341,
"offsetInEndSection": 579,
"text": "A potential shift in the treatment paradigm of MS involving endovascular balloon angioplasty or venous stent placement has been proposed as well as conducted in small patient series. In some cases, it may have resulted in serious injury. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20373339",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1052,
"offsetInEndSection": 1264,
"text": " At present, invasive and potentially dangerous endovascular procedures as therapy for patients with MS should be discouraged until such studies have been completed, analyzed, and debated in the scientific arena.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20373339",
"endSection": "abstract"
},
{
"offsetInBeginSection": 730,
"offsetInEndSection": 1125,
"text": "She underwent percutaneous balloon angioplasty of the associated chronic cerebrospinal venous insufficiency (CCSVI), due to membranous obstruction of the proximal azygous vein, with severe stenosis of the left internal jugular vein. Treatment of the associated CCSVI made a parallel improvement in both clinical and neurophysiological parameters, allowing us to avoid high dose steroid therapy. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20351675",
"endSection": "abstract"
},
{
"offsetInBeginSection": 2113,
"offsetInEndSection": 2352,
"text": "CONCLUSIONS: PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19958985",
"endSection": "abstract"
},
{
"offsetInBeginSection": 799,
"offsetInEndSection": 996,
"text": "In particular, the potential shift in treatment concepts possibly leading to an interventional treatment approach including balloon angioplasty and venous stent placement is currently being debated",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21487978",
"endSection": "abstract"
}
] |
54f42f2764850a5854000005 | Are the Fanconi anemia genes a part of the same signalling pathway? | The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNA | [
"23333482",
"15611632",
"21557222",
"11157805",
"10088637",
"20407210",
"17387268"
] | yesno | [
{
"offsetInBeginSection": 217,
"offsetInEndSection": 285,
"text": "Mutations in at least 14 different genes have been shown to cause FA",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21557222",
"endSection": "abstract"
},
{
"offsetInBeginSection": 427,
"offsetInEndSection": 519,
"text": "The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNA",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21557222",
"endSection": "abstract"
},
{
"offsetInBeginSection": 428,
"offsetInEndSection": 630,
"text": " The current review describes the structure and function of the Fanconi anemia genes and describes the role of the encoded Fanconi anemia proteins in a cellular pathway controlling chromosome stability.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10088637",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 203,
"text": "Fanconi anemia (FA) is a rare human genetic disease caused by mutations in any one of 13 known genes that encode proteins functioning in one common signaling pathway, the FA pathway, or in unknown genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20407210",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 140,
"text": "Fanconi anemia (FA) is a rare inherited recessive disease caused by mutations in one of fifteen genes known to encode FA pathway components.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23333482",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 180,
"text": "Fanconi anemia (FA) proteins function in a DNA damage response pathway that appears to be part of the network including breast cancer susceptibility gene products, BRCA1 and BRCA2.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15611632",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 179,
"text": "Fanconi anemia (FA) proteins function in a DNA damage response pathway that appears to be part of the network including breast cancer susceptibility gene products, BRCA1 and BRCA2",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15611632",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 202,
"text": "Fanconi anemia (FA) is a rare human genetic disease caused by mutations in any one of 13 known genes that encode proteins functioning in one common signaling pathway, the FA pathway, or in unknown genes",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20407210",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 118,
"text": "The Fanconi anemia (FA) gene family comprises at least 12 genes interacting in a common pathway involved in DNA repair",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17387268",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1171,
"offsetInEndSection": 1396,
"text": "These findings show that the newly identified FANCE protein is an integral part of the FA pathway, and support the concept of a functional link between all known proteins encoded by the genes that are mutated in this disorder",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11157805",
"endSection": "abstract"
}
] |
56f160a52ac5ed1459000013 | Are there clinical trials using stem cells for the treatment of cardiac disease? | Yes, there exists clinical trials for cardiac stem cell based treatment. | [
"23746978",
"25858066",
"25984329",
"19804333",
"25169179",
"23773460",
"17198039",
"20560035",
"20680811",
"19907881",
"17888423",
"21526485",
"19022705",
"22405796",
"15030272",
"16969166",
"19857353",
"25205213",
"21749886",
"22943934",
"19627664",
"15692093",
"25145464",
"18543793",
"14647535",
"26259288"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 242,
"text": "Therapy with mesenchymal stem cells is one of the promising tools to improve outcomes after myocardial infarction. Adipose-derived stem cells (ASCs) are an ideal source of mesenchymal stem cells due to their abundance and ease of preparation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25205213",
"endSection": "abstract"
},
{
"offsetInBeginSection": 759,
"offsetInEndSection": 866,
"text": "Furthermore, several ongoing clinical trials using ASCs are producing promising results for heart diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25205213",
"endSection": "abstract"
},
{
"offsetInBeginSection": 297,
"offsetInEndSection": 485,
"text": "Among the cell types under investigation, adult mesenchymal stem cells are widely studied, and in early stage, clinical studies show promise for repair and regeneration of cardiac tissues.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25858066",
"endSection": "abstract"
},
{
"offsetInBeginSection": 816,
"offsetInEndSection": 1123,
"text": " Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25858066",
"endSection": "abstract"
},
{
"offsetInBeginSection": 772,
"offsetInEndSection": 867,
"text": "several ongoing clinical trials using ASCs are producing promising results for heart diseases. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25205213",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 73,
"text": "Clinical application of adult stem cells for therapy for cardiac disease.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23773460",
"endSection": "title"
},
{
"offsetInBeginSection": 99,
"offsetInEndSection": 712,
"text": "Stem cell-based therapies have the potential to fundamentally transform the treatment of ischemic cardiac injury and heart failure by achieving what would have been unthinkable only a few years ago-the Holy Grail of myocardial regeneration. Recent therapeutic approaches involve bone marrow (BM)-derived mononuclear cells and their subsets such as mesenchymal stem/stromal cells (MSCs), endothelial progenitor cells as well as adipose tissue-derived MSCs, cardiac tissue-derived stem cells, and cell combinations. Clinical trials employing these cells have demonstrated that cellular therapy is feasible and safe.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25145464",
"endSection": "abstract"
},
{
"offsetInBeginSection": 817,
"offsetInEndSection": 1122,
"text": "Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25858066",
"endSection": "abstract"
},
{
"offsetInBeginSection": 211,
"offsetInEndSection": 486,
"text": "se of stem and precursor cells as a therapeutic agent for chronically injured organs. Among the cell types under investigation, adult mesenchymal stem cells are widely studied, and in early stage, clinical studies show promise for repair and regeneration of cardiac tissues. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25858066",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 146,
"text": "Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25169179",
"endSection": "abstract"
},
{
"offsetInBeginSection": 715,
"offsetInEndSection": 828,
"text": "Small uncontrolled clinical trials have demonstrated cardiac stem cells as a treatment option for cardiomyopathy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17198039",
"endSection": "abstract"
},
{
"offsetInBeginSection": 366,
"offsetInEndSection": 600,
"text": "Stem cell populations are rapidly increasing, and we are still in the search of optimal cell types to use in clinical trials as bone marrow stem cells did not show significant improvement in cardiac function following transplantation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20560035",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1138,
"offsetInEndSection": 1329,
"text": "Several clinical trials using adult stem cell have shown improvements in cardiac function, however, the mechanism of their action is unclear and widespread tissue regeneration is not evident.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19022705",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1795,
"offsetInEndSection": 1933,
"text": "As we await results from larger and more prolonged clinical trials, the science of stem cell therapy in cardiac disease keeps progressing.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19804333",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 83,
"text": "Stem cell therapy for treatment of cardiac disease has shown therapeutic potential.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16969166",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1515,
"offsetInEndSection": 1617,
"text": "It should be noted that stem cell therapy is not limited to the treatment of ischemic cardiac disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14647535",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 145,
"text": "Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25169179",
"endSection": "abstract"
},
{
"offsetInBeginSection": 288,
"offsetInEndSection": 431,
"text": "This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25169179",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 126,
"text": "Cell transplantation to repair or regenerate injured myocardium is a new frontier in the treatment of cardiovascular disease. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17888423",
"endSection": "abstract"
},
{
"offsetInBeginSection": 54,
"offsetInEndSection": 411,
"text": "Current therapies only delay progression of the cardiac disease or replace the diseased heart with cardiac transplantation. Stem cells represent a recently discovered novel approach to the treatment of cardiac failure that may facilitate the replacement of diseased cardiac tissue and subsequently lead to improved cardiac function and cardiac regeneration.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19857353",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 290,
"text": " Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25169179",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 84,
"text": "Stem cell therapy for treatment of cardiac disease has shown therapeutic potential.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16969166",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 290,
"text": "Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25169179",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1426,
"offsetInEndSection": 1626,
"text": "It should be noted that stem cell therapy is not limited to the treatment of ischemic cardiac disease. Non-ischemic cardiomyopathy, peripheral vascular disease, and aging may be treated by stem cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14647535",
"endSection": "abstract"
},
{
"offsetInBeginSection": 641,
"offsetInEndSection": 794,
"text": " Recent clinical trials have achieved favorable initial endpoints with improvements in cardiac function and clinical symptoms following cellular therapy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25984329",
"endSection": "abstract"
},
{
"offsetInBeginSection": 476,
"offsetInEndSection": 716,
"text": "we consider how cardiac stem cell biology has led us into clinical trials, and we suggest that achieving true cardiac regeneration in patients may ultimately require resolution of critical controversies in experimental cardiac regeneration.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23746978",
"endSection": "abstract"
},
{
"offsetInBeginSection": 441,
"offsetInEndSection": 707,
"text": "Cell-based therapies and tissue engineering provide new promising platforms to develop upcoming therapeutic options. Initial clinical trials were able to generate promising results. A variety of different stem cell types have been used for the clinical application. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23773460",
"endSection": "abstract"
},
{
"offsetInBeginSection": 161,
"offsetInEndSection": 401,
"text": " Insights gained from clinical trials of adult stem cells, together with fundamental scientific advances in cardiac stem cell and regenerative biology, are beginning to yield potential new targets and strategies for regenerative therapies. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22405796",
"endSection": "abstract"
},
{
"offsetInBeginSection": 289,
"offsetInEndSection": 494,
"text": "Early animal trials have demonstrated the ability to improve cardiac function by transfer of HSCs into the myocardium, and early human studies have demonstrated the feasibility and safety of this approach.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21749886",
"endSection": "abstract"
}
] |
54d9f7894b1fd0d33c00000a | Is DNA methylation an epigenetic modification of chromatin related to gene expression? | Epigenetic changes such as DNA methylation alter gene expression at the level of transcription by upregulating, downregulating, or silencing genes completely. | [
"25512710",
"25514241",
"25534027",
"22359296",
"22078060",
"25437055",
"25531272",
"22922032",
"23604474",
"22992936"
] | yesno | [
{
"offsetInBeginSection": 21,
"offsetInEndSection": 164,
"text": "DNA methylation is a chemical modification of DNA involved in the regulation of gene expression by controlling the access to the DNA sequence. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25531272",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 163,
"text": "Epigenetic marks such as DNA methylation play important biological roles in gene expression regulation and cellular differentiation during development.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25534027",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 196,
"text": "DNA methylation patterns are characterized by highly conserved developmental programs, but allow for divergent gene expression resulting from stochastic epigenetic drift or divergent environments.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25437055",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "DNA methylation plays a critical role in the regulation of gene expression. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25514241",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 198,
"text": "Epigenetic changes such as DNA methylation and histone methylation and acetylation alter gene expression at the level of transcription by upregulating, downregulating, or silencing genes completely.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25512710",
"endSection": "abstract"
},
{
"offsetInBeginSection": 199,
"offsetInEndSection": 358,
"text": "Dysregulation of epigenetic events can be pathological, leading to cardiovascular disease, neurological disorders, metabolic disorders, and cancer development.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25512710",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 122,
"text": "DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22922032",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 138,
"text": "Epigenetic control, which includes DNA methylation and histone modifications, leads to chromatin remodeling and regulated gene expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23604474",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 240,
"text": "Epigenetic modifications on the DNA sequence (DNA methylation) or on chromatin-associated proteins (i.e., histones) comprise the \"cellular epigenome\"; together these modifications play an important role in the regulation of gene expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22992936",
"endSection": "abstract"
},
{
"offsetInBeginSection": 136,
"offsetInEndSection": 426,
"text": "Epigenetics is a process involved in gene regulation, mediated via DNA methylation, histone modification, chromatin remodeling, and functional noncoding RNAs, which influences the accessibility of the underlying DNA to transcriptional regulatory factors that activate or repress expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22359296",
"endSection": "abstract"
},
{
"offsetInBeginSection": 101,
"offsetInEndSection": 322,
"text": "Significant progress has been made in the basic understanding of how various epigenetic changes such as DNA methylation, histone modification, miRNA expression, and higher order chromatin structure affect gene expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22078060",
"endSection": "abstract"
}
] |
553bd2f0f321868558000008 | Is Growth factor independence 1b (GFI1B) important for hematopoiesis? | Yes. Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis. Gfi-1b(-/-) embryonic stem cells fail to contribute to red cells of adult chimeras. Gfi-1b(-/-) embryos exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce definitive enucleated erythrocytes. | [
"23308270",
"22699452",
"14530176",
"19773260",
"19958752",
"12351384",
"24800817",
"18224412",
"20124515",
"22668850",
"17707228",
"21606163",
"11825872",
"22960038",
"21732494",
"16397623",
"21170035",
"22885124",
"15507521",
"20143233",
"16177182",
"20861919",
"17095621",
"20826720",
"22399799"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 252,
"text": "Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038",
"endSection": "abstract"
},
{
"offsetInBeginSection": 872,
"offsetInEndSection": 974,
"text": "gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors,",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1151,
"offsetInEndSection": 1197,
"text": "gfi1b is required for definitive hematopoiesis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1052,
"offsetInEndSection": 1140,
"text": "LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 112,
"text": "GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22668850",
"endSection": "title"
},
{
"offsetInBeginSection": 856,
"offsetInEndSection": 1076,
"text": " Taken together, our findings demonstrate a critical and specific role of the GFI1 transcription factors in the first steps of the process leading to the generation of hematopoietic progenitors from hemogenic endothelium",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22668850",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 57,
"text": "A short Gfi-1B isoform controls erythroid differentiation",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22399799",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 105,
"text": "Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22399799",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1070,
"offsetInEndSection": 1162,
"text": "Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21606163",
"endSection": "abstract"
},
{
"offsetInBeginSection": 722,
"offsetInEndSection": 922,
"text": "This reversible modulation of endothelial-haematopoietic state is accomplished by targeting key haematopoietic transcription factors for downregulation, including Runx1, Gata1, Gfi1B, Ikaros, and PU.1",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21170035",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 47,
"text": "Gfi1 and Gfi1b: key regulators of hematopoiesis",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20861919",
"endSection": "title"
},
{
"offsetInBeginSection": 630,
"offsetInEndSection": 851,
"text": "we review how Gfi1 and its paralogue Gfi1b control the development of blood cells, discuss how changes in Gfi1 and Gfi1b function contribute to hematological disease and report on the molecular function of these proteins.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20861919",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 155,
"text": "Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 119,
"text": "Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "abstract"
},
{
"offsetInBeginSection": 121,
"offsetInEndSection": 312,
"text": "Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "abstract"
},
{
"offsetInBeginSection": 314,
"offsetInEndSection": 509,
"text": "We here show that, in humans, Gfi-1B controls the development of erythrocytes and megakaryocytes by regulating the proliferation and differentiation of bipotent erythro-megakaryocytic progenitors",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1509,
"offsetInEndSection": 1677,
"text": "To date, we have identified two common integration sites involving genes encoding transcription factors that play a critical role in hematopoiesis (Evi1 and Gfi1b loci)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19958752",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 304,
"text": "Transcription factors play essential roles in both normal and malignant hematopoiesis. This is the case for the growth factor independent 1b (GFI1B) transcription factor, which is required for erythroid and megakaryocytic differentiation and over-expressed in leukemic patients and cell lines",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19773260",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1022,
"offsetInEndSection": 1450,
"text": "We localized several conserved non-coding elements containing multiple erythroid specific transcription factor binding sites at the GFI1B locus. In GFI1B-expressing cells a subset of these conserved non-coding elements and the promoter adopt a close spatial conformation, localize with open chromatin sites, harbor chromatin modifications associated with gene activation and bind multiple transcription factors and co-repressors",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19773260",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1464,
"offsetInEndSection": 1552,
"text": "Our findings indicate that GFI1B regulatory elements behave as activators and repressors",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19773260",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 216,
"text": "To investigate the molecular effects of growth factor independence 1B (Gfi-1B), a transcription factor essential for the development of hematopoietic cells and differentiation of erythroid and megakaryocytic lineages",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18224412",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1760,
"offsetInEndSection": 1877,
"text": "Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18224412",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 142,
"text": "Gfi-1 and Gfi-1b are homologous transcriptional repressors involved in diverse developmental contexts, including hematopoiesis and oncogenesis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17707228",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17095621",
"endSection": "title"
},
{
"offsetInBeginSection": 546,
"offsetInEndSection": 958,
"text": "We found highly dynamic expression patterns of Gfi1b in erythroid cells, megakaryocytes, and their progenitor cells (MEPS) where Gfi1 is not detected. Vice versa, Gfi1b could not be found in granulocytes, activated macrophages, or their granulomonocytic precursors (GMPs) or in mature naive or activated lymphocytes where Gfi1 is expressed, suggesting a complementary regulation of both loci during hematopoiesis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17095621",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 49,
"text": "Gfi1 and Gfi1b act equivalently in haematopoiesis",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16397623",
"endSection": "title"
},
{
"offsetInBeginSection": 668,
"offsetInEndSection": 814,
"text": "our findings show that an intact SNAG domain is essential for all functions of Gfi1 and that Gfi1b can replace Gfi1 functionally in haematopoiesis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16397623",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 35,
"text": "Gfi-1 oncoproteins in hematopoiesis",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14530176",
"endSection": "title"
},
{
"offsetInBeginSection": 101,
"offsetInEndSection": 239,
"text": "Recent gene targeting experiments and mutational screening in humans have revealed an essential role for Gfi-1 and Gfi-1B in hematopoiesis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14530176",
"endSection": "abstract"
},
{
"offsetInBeginSection": 608,
"offsetInEndSection": 747,
"text": "Gfi-1B disruption is embryonic lethal due to a block of erythropoiesis. Gfi-1B is required for both erythroid and megakaryocyte development",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14530176",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 92,
"text": "Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12351384",
"endSection": "title"
},
{
"offsetInBeginSection": 62,
"offsetInEndSection": 222,
"text": " we identified that the expression of Gfi-1B (growth factor independence-1B) is highly restricted to hematopoietic stem cells, erythroblasts, and megakaryocytes",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12351384",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1470,
"offsetInEndSection": 1665,
"text": "These findings establish Gfi-1B as a novel erythroid regulator and reveal its specific involvement in the regulation of erythroid cell growth through modulating erythroid-specific gene expression",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12351384",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 111,
"text": "The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11825872",
"endSection": "title"
},
{
"offsetInBeginSection": 112,
"offsetInEndSection": 237,
"text": "we establish that Gfi-1b is required for the development of two related blood lineages, erythroid and megakaryocytic, in mice",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11825872",
"endSection": "abstract"
},
{
"offsetInBeginSection": 239,
"offsetInEndSection": 475,
"text": "Gfi-1b(-/-) embryonic stem cells fail to contribute to red cells of adult chimeras. Gfi-1b(-/-) embryos exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce definitive enucleated erythrocytes",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11825872",
"endSection": "abstract"
},
{
"offsetInBeginSection": 623,
"offsetInEndSection": 714,
"text": "Gfi-1b is an essential transcriptional regulator of erythroid and megakaryocyte development",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11825872",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 120,
"text": "Growth factor independence 1b (GFI1B) is a DNA binding repressor of transcription with vital functions in hematopoiesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24800817",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1060,
"offsetInEndSection": 1191,
"text": "Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 150,
"text": "Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17095621",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 48,
"text": "Gfi1 and Gfi1b: key regulators of hematopoiesis.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20861919",
"endSection": "title"
},
{
"offsetInBeginSection": 713,
"offsetInEndSection": 826,
"text": "We show that gfi1aa and gfi1b are expressed in the primitive and definitive sites of hematopoiesis in zebrafish.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038",
"endSection": "abstract"
},
{
"offsetInBeginSection": 119,
"offsetInEndSection": 312,
"text": "Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 139,
"text": "Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24800817",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 131,
"text": "Growth factor-independence 1b (Gfi1b) is a zinc finger transcription factor essential for erythroid and megakaryocytic development.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20143233",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 147,
"text": "Gfi1b (growth factor independence 1b) is a zinc finger transcription factor essential for development of the erythroid and megakaryocytic lineages.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23308270",
"endSection": "abstract"
},
{
"offsetInBeginSection": 683,
"offsetInEndSection": 1072,
"text": "In fact, we demonstrate that VPA treatment is able to induce the expression of growth factor-independent protein 1B (GFI1B) and of mixed-lineage leukemia translocated to chromosome 3 protein (MLLT3), which are crucial regulators of erythrocyte and megakaryocyte differentiation, and that the up-regulation of these genes is mediated by the histone hyperacetylation at their promoter sites.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22885124",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 120,
"text": "Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 150,
"text": "Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays an essential role in erythropoiesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16177182",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 125,
"text": "Evidence that growth factor independence 1b regulates dormancy and peripheral blood mobilization of hematopoietic stem cells.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20826720",
"endSection": "title"
},
{
"offsetInBeginSection": 263,
"offsetInEndSection": 455,
"text": "We report here that adult mice conditionally deficient for the transcription Growth factor independence 1b (Gfi1b) show a significant expansion of functional HSCs in the bone marrow and blood.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20826720",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 130,
"text": "Growth factor-independence 1b (Gfi1b) is a zinc finger transcription factor essential for erythroid and megakaryocytic development",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20143233",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 105,
"text": "Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays an essential role in erythropoiesis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16177182",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1760,
"offsetInEndSection": 1878,
"text": "Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18224412",
"endSection": "abstract"
},
{
"offsetInBeginSection": 263,
"offsetInEndSection": 454,
"text": "We report here that adult mice conditionally deficient for the transcription Growth factor independence 1b (Gfi1b) show a significant expansion of functional HSCs in the bone marrow and blood",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20826720",
"endSection": "abstract"
}
] |
56ed0ba22ac5ed1459000007 | Has Revlimid been approved by the US Food and Drug Administration? | Yes, Revlimid has been approved by the US Food and Drug Administration for treatment of multiple myeloma. | [
"25188481",
"17996589",
"25188483",
"23545923",
"17076650",
"17076653",
"20425391",
"17242661",
"18922829",
"22650376",
"17020458",
"20359632"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 461,
"text": "In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25188483",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 290,
"text": "In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25188481",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 289,
"text": "In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25188481",
"endSection": "abstract"
},
{
"offsetInBeginSection": 697,
"offsetInEndSection": 941,
"text": "Thalidomide, lenalidomide (Revlimid), and bortezomib (Velcade) are directed not only at MM cells but also at the BM milieu and have moved rapidly from the bench to the bedside and United States Food and Drug Administration approval to treat MM.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17996589",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 303,
"text": "Lenalidomide (CC-5013, Revlimid; Celgene Corporation, Summit, NJ), a thalidomide analogue, was granted approval by the U.S. Food and Drug Administration (FDA) on June 29, 2006, for use in combination with dexamethasone in patients with multiple myeloma (MM) who have received at least one prior therapy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18922829",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 280,
"text": "Lenalidomide, an IMiD drug (a novel type of immunomodulating drug) was recently approved by the US Food and Drug Administration for the treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS) and interstitial deletions of chromosome 5q [del(5q)]",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17242661",
"endSection": "abstract"
},
{
"offsetInBeginSection": 309,
"offsetInEndSection": 537,
"text": "Lenalidomide, a second-generation immunomodulatory drug (IMiD), is approved by the US Food and Drug Administration for treatment of transfusion-dependent anemia in lower-risk MDS patients with deletion 5q chromosomal abnormality",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20425391",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 290,
"text": "In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25188481",
"endSection": "abstract"
},
{
"offsetInBeginSection": 35,
"offsetInEndSection": 129,
"text": "lenalidomide (CC5103 or revlimid) are recently approved for the treatment of multiple myeloma.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22650376",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 462,
"text": " In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25188483",
"endSection": "abstract"
}
] |
51724fca8ed59a060a000013 | Which is the execution time (complexity) of the Smith-Waterman algorithm for the alignment of two sequences | The complexity of the Smith-Waterman dynamic programming algorithm is quadratic, that is, it runs in time proportional to the product of lengths of the sequences being aligned. | [
"16522182",
"14668231",
"12804086",
"11301301",
"9021270",
"1774068",
"20370891",
"21714130"
] | factoid | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 251,
"text": "The problem of finding an optimal structural alignment for a pair of superimposed proteins is often amenable to the Smith-Waterman dynamic programming algorithm, which runs in time proportional to the product of lengths of the sequences being aligned.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21714130",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 531,
"offsetInEndSection": 781,
"text": "While this result is not an asymptotic improvement over the original Smith-Waterman algorithm, its complexity is characterized in terms of some sparse features of the matrix and it yields the fastest software implementation to date for such searches.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12804086",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1269,
"offsetInEndSection": 1804,
"text": "If we use N, M and C to represent the size of an amino acid sequence, the size of a structure template, and the maximum cut size of long-range interactions, respectively, the algorithm finds an optimal structure-sequence alignment in O(21C NM) time, a polynomial function of N and M when C = O(log(N + M)). When running on structure-sequence alignment problems without long-range intersections, i.e. C = 0, the algorithm achieves the same asymptotic computational complexity of the Smith-Waterman sequence-sequence alignment algorithm.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9021270",
"endSection": "sections.0"
},
{
"offsetInBeginSection": 1277,
"offsetInEndSection": 1470,
"text": "The algorithm is based on fractional programming and its running time is O(n2log n). In practice, normalized local alignment is only 3-5 times slower than the standard Smith-Waterman algorithm.",
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11301301",
"endSection": "sections.0"
}
] |
56bcc455d36b5da378000003 | List mutations that are implicated in the Gray Platelet Syndrome. | GFI1B and NBEAL2 mutations are implicated in the Gray Platelet Syndrome. | [
"23861251",
"25258341",
"24325358",
"21765413",
"21765412",
"23100277"
] | list | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 64,
"text": "A dominant-negative GFI1B mutation in the gray platelet syndrome",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358",
"endSection": "title"
},
{
"offsetInBeginSection": 145,
"offsetInEndSection": 314,
"text": "We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358",
"endSection": "abstract"
},
{
"offsetInBeginSection": 155,
"offsetInEndSection": 280,
"text": "The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23100277",
"endSection": "abstract"
},
{
"offsetInBeginSection": 110,
"offsetInEndSection": 302,
"text": "Mutations in NBEAL2 underlie gray platelet syndrome (GPS), a rare inherited bleeding disorder characterized by a lack of α-granules within blood platelets and progressive bone marrow fibrosis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25258341",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 98,
"text": "NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet α-granules.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21765412",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21765413",
"endSection": "title"
},
{
"offsetInBeginSection": 301,
"offsetInEndSection": 493,
"text": "Mutations in NBEAL2 underlie gray platelet syndrome (GPS), a rare inherited bleeding disorder characterized by a lack of α-granules within blood platelets and progressive bone marrow fibrosis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25258341",
"endSection": "abstract"
},
{
"offsetInBeginSection": 278,
"offsetInEndSection": 402,
"text": "The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23100277",
"endSection": "abstract"
},
{
"offsetInBeginSection": 749,
"offsetInEndSection": 896,
"text": "Our studies show that GFI1B, in addition to being causally related to the gray platelet syndrome, is key to megakaryocyte and platelet development.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 65,
"text": "A dominant-negative GFI1B mutation in the gray platelet syndrome.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358",
"endSection": "title"
},
{
"offsetInBeginSection": 313,
"offsetInEndSection": 482,
"text": "We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358",
"endSection": "abstract"
},
{
"offsetInBeginSection": 136,
"offsetInEndSection": 283,
"text": "GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2(-/-) mouse. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23861251",
"endSection": "abstract"
},
{
"offsetInBeginSection": 136,
"offsetInEndSection": 370,
"text": "Here we show that mutations in NBEAL2 (neurobeachin-like 2), which encodes a BEACH/ARM/WD40 domain protein, cause GPS and that megakaryocytes and platelets from individuals with GPS express a unique combination of NBEAL2 transcripts. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21765412",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 280,
"text": " The gray platelet syndrome is a rare inherited bleeding disorder characterized by macrothrombocytopenia and deficiency of alpha (α)-granules in platelets. The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23100277",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 280,
"text": "The gray platelet syndrome is a rare inherited bleeding disorder characterized by macrothrombocytopenia and deficiency of alpha (α)-granules in platelets. The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23100277",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 315,
"text": "The gray platelet syndrome is a hereditary, usually autosomal recessive bleeding disorder caused by a deficiency of alpha granules in platelets. We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358",
"endSection": "abstract"
},
{
"offsetInBeginSection": 111,
"offsetInEndSection": 169,
"text": "Mutations in NBEAL2 underlie gray platelet syndrome (GPS),",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25258341",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 315,
"text": " The gray platelet syndrome is a hereditary, usually autosomal recessive bleeding disorder caused by a deficiency of alpha granules in platelets. We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358",
"endSection": "abstract"
}
] |
56f1547c2ac5ed1459000010 | Has single guide RNA been used on human cells? | Yes, sgRNA has been used in human cell lines. | [
"24336569",
"23873081",
"25122746",
"24870050",
"25048165",
"25759096",
"24136345",
"24770324",
"23907171",
"23940360",
"23999092"
] | yesno | [
{
"offsetInBeginSection": 597,
"offsetInEndSection": 719,
"text": "We used a library containing 73,000 sgRNAs to generate knockout collections and performed screens in two human cell lines.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24336569",
"endSection": "abstract"
},
{
"offsetInBeginSection": 353,
"offsetInEndSection": 583,
"text": "Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23907171",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 248,
"text": "The type II CRISPR/Cas system from Streptococcus pyogenes and its simplified derivative, the Cas9/single guide RNA (sgRNA) system, have emerged as potent new tools for targeted gene knockout in bacteria, yeast, fruit fly, zebrafish and human cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23999092",
"endSection": "abstract"
},
{
"offsetInBeginSection": 124,
"offsetInEndSection": 355,
"text": "Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23907171",
"endSection": "abstract"
},
{
"offsetInBeginSection": 381,
"offsetInEndSection": 629,
"text": "Using synthetic single RNA guides, Cas9 can be reprogrammed to create specific double-stranded DNA breaks in the genomes of a variety of organisms, ranging from human cells to bacteria, and thus constitutes a powerful tool for genetic engineering. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25048165",
"endSection": "abstract"
},
{
"offsetInBeginSection": 125,
"offsetInEndSection": 355,
"text": "Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23907171",
"endSection": "abstract"
}
] |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.