PMID
int64 275k
40M
| DateCompleted
stringdate 1965-11-14 00:00:00
2025-02-28 00:00:00
⌀ | DateRevised
stringdate 2000-12-18 00:00:00
2025-02-28 00:00:00
| ISSN
stringlengths 9
9
⌀ | JournalTitle
stringlengths 2
239
| ArticleTitle
stringlengths 1
1.99k
⌀ | Authors
stringlengths 3
61.6k
⌀ | Language
stringclasses 47
values | Grants
stringlengths 11
10.6k
⌀ | PublicationTypes
stringlengths 4
259
| Chemicals
stringlengths 3
1.33k
⌀ | CitationSubset
stringclasses 2
values | ArticleIds
stringlengths 6
44.3k
| Abstract
stringlengths 1
16.7k
⌀ | MeshTerms
stringlengths 3
1.18k
⌀ | Keywords
stringlengths 1
17.2k
⌀ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
22,706,282 | 2013-03-05 | 2016-11-25 | 1638-6183 | Biochimie | The suppressive effect of metabotropic glutamate receptor 5 (mGlu5) inhibition on hepatocarcinogenesis. | Wu Yong Le, Wang Nan Nan, Gu Li, Yang Hui Min, Xia Ning, Zhang Hong | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Pyridines, Receptor, Metabotropic Glutamate 5, Receptors, Metabotropic Glutamate, 6-methyl-2-(phenylethynyl)pyridine, Extracellular Signal-Regulated MAP Kinases | IM | 22706282, S0300-9084(12)00240-4, 10.1016/j.biochi.2012.06.006 | Metabotropic glutamate receptors (mGlus) are G-protein-coupled receptors playing an important role in the central nervous system (CNS). Recently, mGlus have been identified in peripheral tissues, and aberrant expression or inhibition of the receptors functions in the development of certain cancers. However, the correlation of mGlu activity with hepatocellular carcinoma (HCC) remains unknown. In this study, we analyzed the effects of inhibiting mGlu5 activity in hepatocarcinoma cell lines and a xenograft model. Inactivation of mGlu5 with 2-Methyl-6-(phenylethyl)-pyridine (MPEP), a specific antagonist of the receptor, caused inhibition of cell growth, migration, and invasion of HepG2 and Bel-7402 cells, assessed by MTT assay, ATP production, wound healing, and Boyden chamber assay, respectively. Moreover, inhibition of tumor growth and the potential metastasis of hepatocellular carcinoma were also found in nude mice. Furthermore, mGlu5-mediated extracellular signal-regulated kinase (ERK) phosphorylation has been found to be partially involved in cell growth and migration, as detected by stimulation of (S)-3,5-Dihydroxyphenylglycine (DHPG), an agonist of the receptor, and blockage of MPEP and U0126, an inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (MEK). These data indicate that inhibiting the activity of mGlu5 has the molecular potential to suppress oncogenic actions by blocking downstream effector molecules. The study suggests that mGlu5 activity may contribute to understanding the development of HCC. | Animals, Apoptosis, Carcinoma, Hepatocellular, Cell Movement, Cell Proliferation, Cell Transformation, Neoplastic, Extracellular Signal-Regulated MAP Kinases, Hep G2 Cells, Humans, Liver Neoplasms, Male, Mice, Neoplasm Invasiveness, Neoplasm Metastasis, Pyridines, Rats, Receptor, Metabotropic Glutamate 5, Receptors, Metabotropic Glutamate | null |
22,706,283 | 2012-12-05 | 2023-01-06 | 1532-298X | The Plant cell | Crystal structure of Arabidopsis cyclophilin38 reveals a previously uncharacterized immunophilin fold and a possible autoinhibitory mechanism. | Vasudevan Dileep, Fu Aigen, Luan Sheng, Swaminathan Kunchithapadam | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Arabidopsis Proteins, Light-Harvesting Protein Complexes, Photosystem II Protein Complex, photosystem II, chlorophyll-binding protein, CP-47, Cyclophilins, cyclophilin 38, Arabidopsis | IM | 22706283, tpc.111.093781, 10.1105/tpc.111.093781, PMC3406915, 10632780, 2059621, 15222740, 15047905, 11058892, 17898163, 14647374, 15377221, 7508125, 17029235, 11719511, 21262798, 9048379, 16355230, 15299926, 9757107, 1758883, 21087465, 27754618, 11826309, 15051864, 19717822, 2025413, 16511242, 17655280, 8254721, 1400439, 17909185, 16765949, 17476261, 12871165, 15028209, 18445132, 15356344, 9501079, 8621687, 16894144, 15701785, 8377180, 15386017, 10331874, 14871485 | Cyclophilin38 (CYP38) is one of the highly divergent cyclophilins from Arabidopsis thaliana. Here, we report the crystal structure of the At-CYP38 protein (residues 83 to 437 of 437 amino acids) at 2.39-Å resolution. The structure reveals two distinct domains: an N-terminal helical bundle and a C-terminal cyclophilin β-barrel, connected by an acidic loop. Two N-terminal β-strands become part of the C-terminal cyclophilin β-barrel, thereby making a previously undiscovered domain organization. This study shows that CYP38 does not possess peptidyl-prolyl cis/trans isomerase activity and identifies a possible interaction of CYP38 with the E-loop of chlorophyll protein47 (CP47), a component of photosystem II. The interaction of CYP38 with the E-loop of CP47 is mediated through its cyclophilin domain. The N-terminal helical domain is closely packed together with the putative C-terminal cyclophilin domain and establishes a strong intramolecular interaction, thereby preventing the access of the cyclophilin domain to other proteins. This was further verified by protein-protein interaction assays using the yeast two-hybrid system. Furthermore, the non-Leucine zipper N-terminal helical bundle contains several new elements for protein-protein interaction that may be of functional significance. Together, this study provides the structure of a plant cyclophilin and explains a possible mechanism for autoinhibition of its function through an intramolecular interaction. | Arabidopsis Proteins, Crystallography, X-Ray, Cyclophilins, Light-Harvesting Protein Complexes, Models, Molecular, Photosystem II Protein Complex, Protein Conformation, Protein Folding, Protein Structure, Tertiary, Two-Hybrid System Techniques | null |
22,706,284 | 2012-12-05 | 2021-10-21 | 1532-298X | The Plant cell | The recent evolution of a symbiotic ion channel in the legume family altered ion conductance and improved functionality in calcium signaling. | Venkateshwaran Muthusubramanian, Cosme Ana, Han Lu, Banba Mari, Satyshur Kenneth A, Schleiff Enrico, Parniske Martin, Imaizumi-Anraku Haruko, Ané Jean-Michel | eng | null | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S. | Ion Channels, Plant Proteins, Serine, Alanine, Potassium | IM | 22706284, tpc.112.098475, 10.1105/tpc.112.098475, PMC3406897, 20675572, 17242358, 17173544, 13931291, 20676101, 10516298, 17631529, 21652332, 14963334, 10742046, 18321183, 21223388, 2445972, 18852152, 20507440, 8646776, 15944687, 15980262, 17918620, 10913602, 19641028, 19447668, 16452143, 21209659, 15616514, 18978069, 7813423, 19033527, 10964570, 15695439, 21825141, 19106374, 19700563, 8811188, 12423016, 21296053, 15073217, 18055601, 9657381, 9681002, 19279232, 8781233, 20414199, 12368495, 11386364, 18606999, 12011352, 20059702, 17515599, 18208518, 21043574, 15653740, 15882655, 21223389, 12991237, 20880223, 15986921, 11078514 | Arbuscular mycorrhiza and the rhizobia-legume symbiosis are two major root endosymbioses that facilitate plant nutrition. In Lotus japonicus, two symbiotic cation channels, CASTOR and POLLUX, are indispensable for the induction of nuclear calcium spiking, one of the earliest plant responses to symbiotic partner recognition. During recent evolution, a single amino acid substitution in DOES NOT MAKE INFECTIONS1 (DMI1), the POLLUX putative ortholog in the closely related Medicago truncatula, rendered the channel solo sufficient for symbiosis; castor, pollux, and castor pollux double mutants of L. japonicus were rescued by DMI1 alone, while both Lj-CASTOR and Lj-POLLUX were required for rescuing a dmi1 mutant of M. truncatula. Experimental replacement of the critical serine by an alanine in the selectivity filter of Lj-POLLUX conferred a symbiotic performance indistinguishable from DMI1. Electrophysiological characterization of DMI1 and Lj-CASTOR (wild-type and mutants) by planar lipid bilayer experiments combined with calcium imaging in Human Embryonic Kidney-293 cells expressing DMI1 (the wild type and mutants) suggest that the serine-to-alanine substitution conferred reduced conductance with a long open state to DMI1 and improved its efficiency in mediating calcium oscillations. We propose that this single amino acid replacement in the selectivity filter made DMI1 solo sufficient for symbiosis, thus explaining the selective advantage of this allele at the mechanistic level. | Alanine, Amino Acid Substitution, Biological Evolution, Calcium Signaling, Cell Line, Electrophysiological Phenomena, Evolution, Molecular, Fabaceae, Genetic Complementation Test, Humans, Ion Channels, Lotus, Medicago truncatula, Molecular Sequence Data, Mutation, Mycorrhizae, Phylogeny, Plant Proteins, Potassium, Serine, Symbiosis | null |
22,706,285 | 2012-12-05 | 2022-04-08 | 1532-298X | The Plant cell | Redefining C and D in the petunia ABC. | Heijmans Klaas, Ament Kai, Rijpkema Anneke S, Zethof Jan, Wolters-Arts Mieke, Gerats Tom, Vandenbussche Michiel | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Homeodomain Proteins, MADS Domain Proteins, Plant Proteins, Transcription Factors, floral-binding protein 11, Petunia | IM | 22706285, tpc.112.097030, 10.1105/tpc.112.097030, PMC3406901, 21515819, 1346756, 21497757, 20176954, 8100547, 12840762, 8106081, 21810995, 15020484, 12782724, 18346192, 19900437, 16151374, 2535466, 9490741, 7580252, 10069079, 17757866, 12366805, 19717616, 16844905, 1356630, 8024787, 8104573, 15634696, 8093684, 14576291, 20956314, 12589434, 10406807, 9165748, 17589508, 8535139, 9611190, 16409381, 11992820, 11846609, 1715520, 18571972, 10783890, 14973163, 1973265, 16428599 | According to the ABC(DE) model for flower development, C-genes are required for stamen and carpel development and floral determinacy, and D-genes were proposed to play a unique role in ovule development. Both C- and D-genes belong to the AGAMOUS (AG) subfamily of MADS box transcription factors. We show that the petunia (Petunia hybrida) C-clade genes PETUNIA MADS BOX GENE3 and FLORAL BINDING PROTEIN6 (FBP6) largely overlap in function, both in floral organ identity specification and floral determinacy, unlike the pronounced subfunctionalization observed in Arabidopsis thaliana and snapdragon (Antirrhinum majus). Some specialization has also evolved, since FBP6 plays a unique role in the development of the style and stigma. Furthermore, we show that the D-genes FBP7 and FBP11 are not essential to confer ovule identity. Instead, this function is redundantly shared among all AG members. In turn, the D-genes also participate in floral determinacy. Gain-of-function analyses suggest the presence of a posttranscriptional C-repression mechanism in petunia, most likely not existing in Arabidopsis. Finally, we show that expression maintenance of the paleoAPETALA3-type B-gene TOMATO MADS BOX GENE6 depends on the activity of C-genes. Taken together, this demonstrates considerable variation in the molecular control of floral development between eudicot species. | Flowers, Gene Expression Regulation, Plant, Genes, Plant, Homeodomain Proteins, MADS Domain Proteins, Molecular Sequence Data, Mutation, Ovule, Petunia, Plant Proteins, Plants, Genetically Modified, Transcription Factors | null |
22,706,286 | 2012-12-05 | 2024-03-18 | 1532-298X | The Plant cell | Nicotianamine functions in the Phloem-based transport of iron to sink organs, in pollen development and pollen tube growth in Arabidopsis. | Schuler Mara, Rellán-Álvarez Rubén, Fink-Straube Claudia, Abadía Javier, Bauer Petra | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Citrates, nicotianamine, Azetidinecarboxylic Acid, Iron, Zinc | IM | 22706286, tpc.112.099077, 10.1105/tpc.112.099077, PMC3406910, 16667646, 9618566, 11479325, 17351051, 21619056, 12172022, 15315637, 15255869, 22218421, 18957258, 19073647, 18498676, 12228472, 20625001, 16815956, 19304929, 22374395, 15255870, 19702755, 11092880, 12782722, 20128878, 10748254, 10069850, 18421700, 10491178, 16479550, 16362328, 18977764, 21915334, 12084823, 20080803, 22374397, 11983700, 21447758, 19377460, 20007440, 18083798, 21742986, 15350397, 19188276, 16297069, 17516080, 9952442, 19083175, 11201743, 15310833, 18826427, 12177457, 21693516, 20419136, 15531708, 17600712, 12569395, 15753101, 21592396 | The metal chelator nicotianamine promotes the bioavailability of Fe and reduces cellular Fe toxicity. For breeding Fe-efficient crops, we need to explore the fundamental impact of nicotianamine on plant development and physiology. The quadruple nas4x-2 mutant of Arabidopsis thaliana cannot synthesize any nicotianamine, shows strong leaf chlorosis, and is sterile. To date, these phenotypes have not been fully explained. Here, we show that sink organs of this mutant were Fe deficient, while aged leaves were Fe sufficient. Upper organs were also Zn deficient. We demonstrate that transport of Fe to aged leaves relied on citrate, which partially complemented the loss of nicotianamine. In the absence of nicotianamine, Fe accumulated in the phloem. Our results show that rather than enabling the long-distance movement of Fe in the phloem (as is the case for Zn), nicotianamine facilitates the transport of Fe from the phloem to sink organs. We delimit nicotianamine function in plant reproductive biology and demonstrate that nicotianamine acts in pollen development in anthers and pollen tube passage in the carpels. Since Fe and Zn both enhance pollen germination, a lack of either metal may contribute to the reproductive defect. Our study sheds light on the physiological functions of nicotianamine. | Arabidopsis, Azetidinecarboxylic Acid, Biological Transport, Citrates, Flowers, Gene Expression Regulation, Plant, Iron, Mutation, Phloem, Plant Development, Plant Leaves, Plant Roots, Pollen, Pollen Tube, Zinc | null |
22,706,287 | 2012-12-05 | 2021-10-21 | 1532-298X | The Plant cell | Identification of a photosystem II phosphatase involved in light acclimation in Arabidopsis. | Samol Iga, Shapiguzov Alexey, Ingelsson Björn, Fucile Geoffrey, Crèvecoeur Michèle, Vener Alexander V, Rochaix Jean-David, Goldschmidt-Clermont Michel | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Arabidopsis Proteins, Light-Harvesting Protein Complexes, Photosystem II Protein Complex, Recombinant Proteins, Thylakoid Membrane Proteins, Protein Kinases, light-harvesting complex II kinase, STN8 protein, Arabidopsis, Phosphoprotein Phosphatases, Protein Phosphatase 2C, photosystem II phosphatase, Arabidopsis | IM | 22706287, tpc.112.095703, 10.1105/tpc.112.095703, PMC3406908, 18156295, 18431481, 10198115, 16237446, 9374540, 8224208, 17184728, 19965965, 20028840, 12626117, 19440515, 18774768, 18398051, 20532038, 17186119, 12624266, 16040609, 20176943, 10891285, 21183394, 18709440, 24307030, 18331354, 11005828, 18983262, 1310622, 10555977, 16428265, 21976483, 12437884, 17470368, 21605541, 11850400, 19113838, 18047474, 20217232, 16755288, 11447103, 21915352, 11875433, 21768351, 16081312, 17071959, 20230505, 9064687, 11038603, 20126264, 10357809, 6245872, 15620363, 15729347, 19021904, 17517783, 19575582, 8663006, 17961594, 21108925, 9554956, 12372603, 18328775, 15530359, 12970473, 11113141 | Reversible protein phosphorylation plays a major role in the acclimation of the photosynthetic apparatus to changes in light. Two paralogous kinases phosphorylate subsets of thylakoid membrane proteins. STATE TRANSITION7 (STN7) phosphorylates LHCII, the light-harvesting antenna of photosystem II (PSII), to balance the activity of the two photosystems through state transitions. STN8, which is mainly involved in phosphorylation of PSII core subunits, influences folding of the thylakoid membranes and repair of PSII after photodamage. The rapid reversibility of these acclimatory responses requires the action of protein phosphatases. In a reverse genetic screen, we identified the chloroplast PP2C phosphatase, PHOTOSYSTEM II CORE PHOSPHATASE (PBCP), which is required for efficient dephosphorylation of PSII proteins. Its targets, identified by immunoblotting and mass spectrometry, largely coincide with those of the kinase STN8. The recombinant phosphatase is active in vitro on a synthetic substrate or on isolated thylakoids. Thylakoid folding is affected in the absence of PBCP, while its overexpression alters the kinetics of state transitions. PBCP and STN8 form an antagonistic kinase and phosphatase pair whose substrate specificity and physiological functions are distinct from those of STN7 and the counteracting phosphatase PROTEIN PHOSPHATASE1/THYLAKOID-ASSOCIATED PHOSPHATASE38, but their activities may overlap to some degree. | Acclimatization, Arabidopsis, Arabidopsis Proteins, Chloroplasts, Gene Expression Regulation, Plant, Light, Light-Harvesting Protein Complexes, Molecular Sequence Data, Mutation, Phosphoprotein Phosphatases, Phosphorylation, Photosystem II Protein Complex, Protein Kinases, Protein Phosphatase 2C, Recombinant Proteins, Thylakoid Membrane Proteins | null |
22,706,290 | 2012-11-27 | 2022-02-23 | 1756-591X | Metallomics : integrated biometal science | Efflux function, tissue-specific expression and intracellular trafficking of the Zn transporter ZnT10 indicate roles in adult Zn homeostasis. | Bosomworth Helen J, Thornton Jared K, Coneyworth Lisa J, Ford Dianne, Valentine Ruth A | eng | BB/F019637/1 (Biotechnology and Biological Sciences Research Council, United Kingdom); BBD01669X/2 (Biotechnology and Biological Sciences Research Council, United Kingdom) | Journal Article, Research Support, Non-U.S. Gov't | Cation Transport Proteins, RNA, Messenger, SLC30A8 protein, human, Zinc Transporter 8, Zinc | IM | 22706290, 10.1039/c2mt20088k | Zn is essential to the structure and function of numerous proteins and enzymes so requires tight homeostatic control at both the systemic and cellular level. Two families of Zn transporters - ZIP (SLC39) and ZnT (SLC30) - contribute to Zn homeostasis. There are at least 10 members of the human ZnT family, and the expression profile and regulation of each varies depending on tissue type. Little is known about the role and expression pattern of ZnT10; however in silico data predict restricted expression to foetal tissue. We show a differential expression profile for ZnT10 in adult human tissue by RT-qPCR and detect highest levels of expression in small intestine, liver and brain tissues. We present data revealing the functional activity of ZnT10 to be in the efflux direction. Using a plasmid construct to express ZnT10 with an N-terminal FLAG-epitope tag, we reveal subcellular localisation in a neuroblastoma cell line (SH-SY5Y) to be at the Golgi apparatus under standard conditions of culture, with trafficking to the plasma membrane observed at higher extracellular Zn concentrations. We demonstrate down-regulation by Zn of ZnT10 mRNA levels in cultured intestinal and neuroblastoma cell lines and demonstrate reduced transcription from the ZnT10 promoter at an elevated extracellular Zn concentration. These features of ZnT10 localisation, regulation and function, together with the discovery that ZnT10 is expressed a high levels in brain tissue, indicate that ZnT10 has a role in regulating Zn homeostasis in the brain so may have relevance to the development of neurodegenerative disease. | Brain, Caco-2 Cells, Cation Transport Proteins, Cell Line, Gene Expression, Gene Expression Regulation, Humans, Intestine, Small, Liver, Promoter Regions, Genetic, Protein Transport, RNA, Messenger, Zinc, Zinc Transporter 8 | null |
22,706,288 | 2012-12-05 | 2022-04-08 | 1532-298X | The Plant cell | Ethylene signaling negatively regulates freezing tolerance by repressing expression of CBF and type-A ARR genes in Arabidopsis. | Shi Yiting, Tian Shouwei, Hou Lingyan, Huang Xiaozhen, Zhang Xiaoyan, Guo Hongwei, Yang Shuhua | eng | null | Journal Article, Research Support, Non-U.S. Gov't | ARR15 protein, Arabidopsis, ARR5 protein, Arabidopsis, ARR7 protein, Arabidopsis, Amino Acids, Cyclic, Arabidopsis Proteins, CBF1 protein, Arabidopsis, Cytokinins, DNA-Binding Proteins, DREB1A protein, Arabidopsis, EIL1 protein, Arabidopsis, EIN2 protein, Arabidopsis, EIN3 protein, Arabidopsis, EIN4 protein, Arabidopsis, ETR1 protein, Arabidopsis, Ethylenes, Nuclear Proteins, Receptors, Cell Surface, Trans-Activators, Transcription Factors, 1-aminocyclopropane-1-carboxylic acid, ethylene, aminoethoxyvinylglycine, Glycine | IM | 22706288, tpc.112.098640, 10.1105/tpc.112.098640, PMC3406918, 17855156, 12172015, 2152173, 15012220, 17376166, 14675532, 20663954, 12821658, 7569898, 9215635, 11031228, 21832142, 8431946, 20647342, 16163802, 8938401, 9023378, 15634197, 12672693, 19270186, 18065689, 9576967, 11457973, 16669782, 15469500, 9881163, 7770519, 19948955, 12606727, 18980656, 11169177, 9539813, 11115887, 16400150, 19717619, 20444230, 15044023, 20699401, 18463635, 1834244, 9851977, 9707532, 11089677, 15165189, 14555690, 22108404, 17189334, 9695954, 16702557, 11115899, 16662222, 16798847, 8211181, 9525853, 8148648, 12566591, 15282545, 18466304, 9707537, 7768447, 20463025, 20135196, 17015446, 19621034, 17416732, 14973166, 14675533, 10381874, 17533512, 10648789, 12941880, 19592132 | The phytohormone ethylene regulates multiple aspects of plant growth and development and responses to environmental stress. However, the exact role of ethylene in freezing stress remains unclear. Here, we report that ethylene negatively regulates plant responses to freezing stress in Arabidopsis thaliana. Freezing tolerance was decreased in ethylene overproducer1 and by the application of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid but increased by the addition of the ethylene biosynthesis inhibitor aminoethoxyvinyl glycine or the perception antagonist Ag+. Furthermore, ethylene-insensitive mutants, including etr1-1, ein4-1, ein2-5, ein3-1, and ein3 eil1, displayed enhanced freezing tolerance. By contrast, the constitutive ethylene response mutant ctr1-1 and EIN3-overexpressing plants exhibited reduced freezing tolerance. Genetic and biochemical analyses revealed that EIN3 negatively regulates the expression of CBFs and type-A Arabidopsis response regulator5 (ARR5), ARR7, and ARR15 by binding to specific elements in their promoters. Overexpression of these ARR genes enhanced the freezing tolerance of plants. Thus, our study demonstrates that ethylene negatively regulates cold signaling at least partially through the direct transcriptional control of cold-regulated CBFs and type-A ARR genes by EIN3. Our study also provides evidence that type-A ARRs function as key nodes to integrate ethylene and cytokinin signaling in regulation of plant responses to environmental stress. | Amino Acids, Cyclic, Arabidopsis, Arabidopsis Proteins, Cytokinins, DNA-Binding Proteins, Ethylenes, Freezing, Gene Expression Regulation, Plant, Glycine, Mutation, Nuclear Proteins, Receptors, Cell Surface, Signal Transduction, Stress, Physiological, Trans-Activators, Transcription Factors | null |
22,706,291 | 2012-10-31 | 2020-09-30 | 1944-7884 | Journal of acquired immune deficiency syndromes (1999) | Tolerability of mefloquine intermittent preventive treatment for malaria in HIV-infected pregnant women in Benin. | Denoeud-Ndam Lise, Clément Marie-Caroline, Briand Valérie, Akakpo Jocelyn, Agossou Videhouenou K, Atadokpédé Félix, Dossou-Gbété Lucien, Komongui Didier G, Afangnihoun Aldric, Girard Pierre-Marie, Zannou Djimon-Marcel, Cot Michel | eng | null | Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't | Antimalarials, Mefloquine | IM | 22706291, 10.1097/QAI.0b013e3182615a58 | To investigate the tolerability of mefloquine intermittent preventive treatment (MQ IPTp) for malaria in HIV-infected pregnant women compared with HIV-negative women. | Adult, Antimalarials, Benin, Chemoprevention, Cohort Studies, Drug-Related Side Effects and Adverse Reactions, Female, HIV Infections, Humans, Malaria, Mefloquine, Pregnancy, Pregnancy Complications, Infectious, Prospective Studies | null |
22,706,292 | 2012-10-31 | 2020-09-30 | 1944-7884 | Journal of acquired immune deficiency syndromes (1999) | Initiation of c-ART in HIV-1 infected patients is associated with a decrease of the metabolic activity of the thymus evaluated using FDG-PET/computed tomography. | Lelièvre Jean-Daniel, Melica Giovanna, Itti Emmanuel, Lacabaratz Christine, Rozlan Sandra, Wiedemann Aurélie, Cheynier Rémi, Meignan Michel, Thiebaut Rodolphe, Levy Yves | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Anti-Retroviral Agents | IM | 22706292, 10.1097/QAI.0b013e3182615b62 | The role of the thymus in the depletion or restoration of T-cell pool in HIV infection is still debatable. Studies are hampered by the lack of valuable tools to investigate thymic activity. | Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, HIV Infections, HIV-1, Humans, Multimodal Imaging, Positron-Emission Tomography, Prospective Studies, T-Lymphocytes, Thymus Gland, Tomography, X-Ray Computed | null |
22,706,294 | 2012-10-31 | 2020-09-30 | 1944-7884 | Journal of acquired immune deficiency syndromes (1999) | Cervical human papillomavirus infection and shedding of human immunodeficiency virus in cervicovaginal fluids: a cross-sectional study. | Fornabaio Chiara, Carvalho Anna C C, Lillo Flavia, Fiore José R, Bergamaschi Viviana, Bigoni Sara, Puzzi Petra R, Cristini Graziella, Comelli Mario, Parisi Maria R, Matteelli Alberto | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Anti-Retroviral Agents | IM | 22706294, 10.1097/QAI.0b013e31826327a0 | We evaluated the association between human papillomavirus cervical infection and HIV shedding in cervicovaginal lavage fluid (CVL), studying 89 HIV-infected women recruited at the Department of Infectious Diseases of Brescia (Italy). HIV shedding in CVL was found in a similar proportion of women with (30%; 21/70) and without (31.6%; 6/19) cervical human papillomavirus infection. A statistically significant correlation was found between HIV viral load in serum and CVL among the 27 women with detectable HIV in CVL (r = 0.4; P = 0.04). However, women on highly active antiretroviral therapy were more likely to have detectable HIV-RNA in CVL despite negative viremia (80% vs. 8%; P < 0.005). | Adult, Anti-Retroviral Agents, Blood, Body Fluids, Cervix Uteri, Cross-Sectional Studies, Female, HIV, HIV Infections, Humans, Italy, Middle Aged, Papillomavirus Infections, Vagina, Viral Load, Virus Shedding, Young Adult | null |
22,706,295 | 2012-10-02 | 2021-10-21 | 2210-2612 | International journal of surgery case reports | Unusual case of persistent unilateral pleural effusion secondary to pancreaticopleural fistula. | El-Beialy Hesham, Fernandez Ivo | eng | null | Journal Article | null | null | 22706295, S2210-2612(12)00093-4, 10.1016/j.ijscr.2012.04.018, PMC3398481, 9543587, 21686851, 15767731, 9007433, 9855072 | Pancreaticopleural fistula is rare. It occurs as a complication in acute and chronic pancreatitis. Here we report a case of persistent unilateral pleural effusion secondary to pancreaticopleural fistula. | null | null |
22,706,296 | 2012-10-02 | 2021-10-21 | 2210-2612 | International journal of surgery case reports | Primary biliary tract melanoma: Report of a case and review of the literature. | Smith Nathaniel E, Taube Janis M, Warczynski Tam M, Collier Kevin D, Pawlik Timothy M | eng | null | Journal Article | null | null | 22706296, S2210-2612(12)00102-2, 10.1016/j.ijscr.2012.05.008, PMC3397286, 8771146, 20570171, 14118639, 1929788, 10705398, 8832870, 19168849, 16137472, 13009650, 3793088, 14753603, 11253118, 9921971, 14732666, 1705727, 3347868, 9346549 | Primary melanoma of the bile duct is extremely rare with only nine cases of primary melanoma of the bile duct reported in the literature. | null | null |
22,706,297 | 2012-10-02 | 2021-10-21 | 2210-2612 | International journal of surgery case reports | Appendiceal intussusception to the cecum caused by mucocele of the appendix: Laparoscopic approach. | Laalim Said Ait, Toughai Imane, Benjelloun El Bachir, Majdoub Karim Hassani Ibn, Mazaz Khalid | eng | null | Journal Article | null | null | 22706297, S2210-2612(12)00097-1, 10.1016/j.ijscr.2012.04.019, PMC3397288, 9716778, 6734362, 15954839, 17090846, 22741125, 19249733, 17180673, 15156378, 18435897, 4718184, 22066077, 14972272, 8946609, 15768456, 12740466, 14598408 | Appendiceal intussusception is a very rare disease that is found in only 0.01% of patients who have undergone an appendectomy. Clinical symptoms vary and some patients are asymptomatic. Laparoscopic surgery for appendiceal tumors is still controversial. We present a case of intussusception of the appendix with a mucinous cystadenoma treated by laparoscopic surgery. | null | null |
22,706,298 | 2012-10-02 | 2021-10-21 | 2210-2612 | International journal of surgery case reports | Listeria septicaemia following insertion of a dynamic hip screw: A case report and literature review. | Shahban Shafiq Arif, Manjula Natarajan, Siddiqui Shabih | eng | null | Journal Article | null | null | 22706298, S2210-2612(12)00107-1, 10.1016/j.ijscr.2012.05.012, PMC3397291, 8170424, 18727264, 21430356, 8767708, 14503789, 21836384, 1428333, 21681069, 21851486 | Listeria monocytogenes is a food borne bacterial pathogen which is rarely encountered in the United Kingdom. This rare and potentially life threatening infection has a high mortality rate and therefore requires early antimicrobial intervention. | null | null |
22,706,299 | 2013-08-12 | 2012-11-12 | 1096-3634 | Seminars in cell & developmental biology | Using protein microarrays to study phosphorylation-mediated signal transduction. | Zhang Hong, Pelech Steven | eng | null | Journal Article, Review | Antibodies, Phosphoproteins | IM | 22706299, S1084-9521(12)00110-3, 10.1016/j.semcdb.2012.05.009 | Unraveling the complexity of cell regulatory systems and monitoring their operations under normal and pathological circumstances is one of the major outstanding biomedical challenges. The phosphoproteome has emerged as a rich source of biomarkers for tracking cell signaling and disease, and many of the kinases that phosphorylate proteins represent attractive targets for drug development. Over 100,000 phosphorylation sites distributed in most of the 23,000 proteins encoded by the human genome have already been identified in a non-targeted fashion by mass-spectrometry. Antibody microarrays permit ultra-sensitive, semi-quantitative measurements of the levels of hundreds of target proteins and their phosphorylation in parallel with specimens from cells and tissues. Conversely, reverse-phase protein microarrays (RPPMs) that are printed with crude cell/tissue lysates allow tracking of a target protein with a probing antibody in hundreds to thousands of cell and tissue samples simultaneously. While more than half a million commercial antibodies are available, the identification of highly specific and potent antibodies for use in microarrays remains a major impediment. Antibody cross-reactivity is an issue for both antibody microarrays and RPPMs. The low abundance of signal transduction proteins and their substoichiometric levels of phosphorylation are also problematic. Finally, non-denaturing conditions used with standard antibody microarrays permit protein complexes, which can produce false positives and false negatives. Changes in the level of an interacting protein may be misinterpreted as alterations in the amount of a target protein or its phosphorylation state. It is critical that leads from both types of microarrays are validated by complementary approaches such as immunoblotting and ELISA. More than a hundred reports have appeared in the scientific literature that have benefited from utilization of antibody and protein lysate microarrays. We have highlighted some of the pioneering works in this field and provided recent examples of their successful deployment as tools for broad-based, targeted proteomics research. | Animals, Antibodies, Humans, Phosphoproteins, Phosphorylation, Protein Array Analysis, Proteomics, Signal Transduction | null |
22,706,300 | 2012-09-11 | 2021-10-21 | 1558-8238 | The Journal of clinical investigation | What's in a name? | Weiss Mitchell J, Mason Philip J, Bessler Monica | eng | R01 CA105312 (NCI NIH HHS, United States); R01 CA106995 (NCI NIH HHS, United States); CA106995 (NCI NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Comment | GATA1 Transcription Factor, GATA1 protein, human | IM | 22706300, 63989, 10.1172/JCI63989, PMC3386834, 19513100, 9988267, 22045982, 19887574, 7568185, 19411634, 16783379, 22706301, 20194897, 20713514, 18515656, 18930124, 18641651, 8298126, 19878869, 18671700, 9241274, 15659348 | Mutations in numerous genes encoding ribosomal proteins (RPs) occur in 50%-70% of individuals with Diamond-Blackfan anemia (DBA), establishing the disease as a ribosomopathy. As described in this issue of JCI, Sankaran, Gazda, and colleagues used genome-wide exome sequencing to study DBA patients with no detectable mutations in RP genes. They identified two unrelated pedigrees in which the disease is associated with mutations in GATA1, which encodes an essential hematopoietic transcription factor with no known mechanistic links to ribosomes. These findings ignite an interesting and potentially emotional debate on how we define DBA and whether the term should be restricted to pure ribosomopathies. More generally, the work reflects the powerful knowledge and controversies arising from the deluge of data generated by new genetic technologies that are being used to analyze human diseases. | Anemia, Diamond-Blackfan, Exome, GATA1 Transcription Factor, Humans, Male | null |
22,706,301 | 2012-09-11 | 2022-03-16 | 1558-8238 | The Journal of clinical investigation | Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia. | Sankaran Vijay G, Ghazvinian Roxanne, Do Ron, Thiru Prathapan, Vergilio Jo-Anne, Beggs Alan H, Sieff Colin A, Orkin Stuart H, Nathan David G, Lander Eric S, Gazda Hanna T | eng | R01 HL107558 (NHLBI NIH HHS, United States); T32 HL007574 (NHLBI NIH HHS, United States); U54 HG003067 (NHGRI NIH HHS, United States); T32 HL007574-30 (NHLBI NIH HHS, United States); U54 HG003067-09 (NHGRI NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | GATA1 Transcription Factor, GATA1 protein, human | IM | 22706301, 63597, 10.1172/JCI63597, PMC3386831, 21715302, 10700180, 9988267, 22045982, 21478889, 19182786, 15817467, 20942659, 18671700, 12172547, 20981092, 15895080, 19061985, 18258751, 9192642, 16783379, 2725678, 20960466, 22262766, 20194897, 20116044 | Diamond-Blackfan anemia (DBA) is a hypoplastic anemia characterized by impaired production of red blood cells, with approximately half of all cases attributed to ribosomal protein gene mutations. We performed exome sequencing on two siblings who had no known pathogenic mutations for DBA and identified a mutation in the gene encoding the hematopoietic transcription factor GATA1. This mutation, which occurred at a splice site of the GATA1 gene, impaired production of the full-length form of the protein. We further identified an additional patient carrying a distinct mutation at the same splice site of the GATA1 gene. These findings provide insight into the pathogenesis of DBA, showing that the reduction in erythropoiesis associated with the disease can arise from causes other than defects in ribosomal protein genes. These results also illustrate the multifactorial role of GATA1 in human hematopoiesis. | Anemia, Diamond-Blackfan, Base Sequence, Case-Control Studies, DNA Mutational Analysis, Exome, GATA1 Transcription Factor, Genetic Association Studies, Hematopoiesis, Humans, Male, Real-Time Polymerase Chain Reaction, Sequence Deletion, Young Adult | null |
22,706,303 | 2012-09-11 | 2021-10-21 | 1558-8238 | The Journal of clinical investigation | Disrupted cortical function underlies behavior dysfunction due to social isolation. | Miyazaki Tomoyuki, Takase Kenkichi, Nakajima Waki, Tada Hirobumi, Ohya Daisuke, Sano Akane, Goto Takahisa, Hirase Hajime, Malinow Roberto, Takahashi Takuya | eng | R01 MH049159 (NIMH NIH HHS, United States); R01 MH091119 (NIMH NIH HHS, United States); R37 MH049159 (NIMH NIH HHS, United States); MH049159 (NIMH NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | Glucocorticoids, Receptors, AMPA, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Calcium-Calmodulin-Dependent Protein Kinase Type 2, glutamate receptor ionotropic, AMPA 1, Corticosterone, Norepinephrine | IM | 22706303, 63060, 10.1172/JCI63060, PMC3387818, 19543281, 16504942, 19217372, 11786607, 3526705, 19151710, 15746389, 8210177, 21808020, 15275800, 16783512, 20478875, 16582904, 19234457, 12471636, 18622402, 19455174, 16931756, 3783236, 10553028, 17237803, 12042880, 9530495, 12043845, 7341838, 10731148, 12195431, 11994750, 12031405, 10641758, 14556714, 11252776, 2820370, 10911891, 12049934, 16531997, 12052905, 12640181, 21289533, 20159451, 7917027, 12880790, 15217348, 16611726, 15132438, 16580733, 17290796, 12628184, 19469026, 18701074, 14687553, 17923095, 22197694, 8091215, 19826493, 22197698, 11036266, 21338886, 11502260, 12624270, 21746893, 18635659, 1910574 | Stressful events during early childhood can have a profound lifelong influence on emotional and cognitive behaviors. However, the mechanisms by which stress affects neonatal brain circuit formation are poorly understood. Here, we show that neonatal social isolation disrupts molecular, cellular, and circuit developmental processes, leading to behavioral dysfunction. Neonatal isolation prevented long-term potentiation and experience-dependent synaptic trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors normally occurring during circuit formation in the rodent barrel cortex. This inhibition of AMPA receptor trafficking was mediated by an increase of the stress glucocorticoid hormone and was associated with reduced calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling, resulting in attenuated whisker sensitivity at the cortex. These effects led to defects in whisker-dependent behavior in juvenile animals. These results indicate that neonatal social isolation alters neuronal plasticity mechanisms and perturbs the initial establishment of a normal cortical circuit, which potentially explains the long-lasting behavioral effects of neonatal stress. | Animals, Animals, Newborn, Behavior, Animal, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Corticosterone, Female, Glucocorticoids, Long-Term Potentiation, Male, Neuronal Plasticity, Norepinephrine, Phosphorylation, Protein Processing, Post-Translational, Protein Transport, Rats, Rats, Sprague-Dawley, Receptors, AMPA, Sensory Deprivation, Social Isolation, Somatosensory Cortex, Stress, Psychological, Synaptic Transmission, Touch Perception, Vibrissae, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid | null |
22,706,302 | 2012-09-11 | 2021-10-21 | 1558-8238 | The Journal of clinical investigation | Adenosine augmentation ameliorates psychotic and cognitive endophenotypes of schizophrenia. | Shen Hai-Ying, Singer Philipp, Lytle Nikki, Wei Catherine J, Lan Jing-Quan, Williams-Karnesky Rebecca L, Chen Jiang-Fan, Yee Benjamin K, Boison Detlev | eng | F30 NS070359 (NINDS NIH HHS, United States); R01 MH083973 (NIMH NIH HHS, United States); R01 NS061844 (NINDS NIH HHS, United States); R01MH083973 (NIMH NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural | Amphetamines, Antipsychotic Agents, Morpholines, Pyrimidines, Receptor, Adenosine A2A, ABT 702, Adenosine Kinase, Adenosine | IM | 22706302, 62378, 10.1172/JCI62378, PMC3386823, 21401494, 18005073, 16848689, 11459338, 16039728, 21315743, 16685255, 19682439, 17429216, 17024327, 11549226, 14736855, 9739141, 15888432, 17572452, 17289263, 21693634, 11343875, 12601500, 18634566, 19428218, 14663001, 15006500, 19245705, 16580767, 17332207, 19763139, 18568339, 18172552, 20182058, 18354001, 17015235, 22068054, 15930047, 9342776, 19484222, 15694232, 19785999, 11082453, 9141196, 20414589, 15238994, 10771351, 21701065, 12900046, 11404469, 15797469, 10849191, 19942481, 19639292, 21427729, 17460616, 10978882, 20686195, 7898676, 7688163 | An emerging theory of schizophrenia postulates that hypofunction of adenosine signaling may contribute to its pathophysiology. This study was designed to test the "adenosine hypothesis" of schizophrenia and to evaluate focal adenosine-based strategies for therapy. We found that augmentation of adenosine by pharmacologic inhibition of adenosine kinase (ADK), the key enzyme of adenosine clearance, exerted antipsychotic-like activity in mice. Further, overexpression of ADK in transgenic mice was associated with attentional impairments linked to schizophrenia. We observed that the striatal adenosine A2A receptor links adenosine tone and psychomotor response to amphetamine, an indicator of dopaminergic signaling. Finally, intrastriatal implants of engineered adenosine-releasing cells restored the locomotor response to amphetamine in mice overexpressing ADK, whereas the same grafts placed proximal to the hippocampus of transgenic mice reversed their working memory deficit. This functional double dissociation between striatal and hippocampal adenosine demonstrated in Adk transgenic mice highlights the independent contributions of these two interconnected brain regions in the pathophysiology of schizophrenia and thus provides the rationale for developing local adenosine augmentation therapies for the treatment of schizophrenia. | Adenosine, Adenosine Kinase, Amphetamines, Animals, Antipsychotic Agents, Basal Ganglia, Cell Transplantation, Cells, Cultured, Cognition Disorders, Cricetinae, Disease Models, Animal, Endophenotypes, Hippocampus, Mice, Mice, Inbred C57BL, Mice, Transgenic, Morpholines, Psychotic Disorders, Pyrimidines, Receptor, Adenosine A2A, Schizophrenia, Schizophrenic Psychology | null |
22,706,305 | 2012-09-11 | 2024-04-17 | 1558-8238 | The Journal of clinical investigation | Genetic variation in T-box binding element functionally affects SCN5A/SCN10A enhancer. | van den Boogaard Malou, Wong L Y Elaine, Tessadori Federico, Bakker Martijn L, Dreizehnter Lisa K, Wakker Vincent, Bezzina Connie R, 't Hoen Peter A C, Bakkers Jeroen, Barnett Phil, Christoffels Vincent M | eng | null | Journal Article, Research Support, Non-U.S. Gov't | NAV1.5 Voltage-Gated Sodium Channel, NAV1.8 Voltage-Gated Sodium Channel, SCN10A protein, human, SCN5A protein, human, Scn10a protein, mouse, Scn5a protein, mouse, Sodium Channels, T-Box Domain Proteins, T-box transcription factor 5, Tbx3 protein, mouse | IM | 22706305, 62613, 10.1172/JCI62613, PMC3386824, 20702085, 19498200, 20729851, 8988165, 18626064, 10812473, 20378774, 16075039, 19797194, 21076409, 21486936, 20062060, 18467625, 15898165, 21566215, 10077612, 11752295, 12016259, 8988164, 19131956, 9651244, 11689487, 2557196, 11572777, 19377496, 22419669, 22075998, 15131651, 19736561, 15498808, 11794197, 11972032, 11440973, 18178574, 17603472, 21347284, 21565834, 20062061, 20133910, 19741700, 17008524, 19096026, 18288184, 11748239, 11063699, 12520026, 21538160, 20421888, 15580613, 20622880, 17604724, 20627891, 22130515, 19033363, 21415370, 17473172, 12407185, 22138689, 16285859, 19647421, 17234970, 19369657, 19255801, 22087007, 21576278, 22080862, 15158141, 19212405, 22203979, 20435671, 18287630, 17971780, 19118284, 19653328, 20062063, 21454796 | The contraction pattern of the heart relies on the activation and conduction of the electrical impulse. Perturbations of cardiac conduction have been associated with congenital and acquired arrhythmias as well as cardiac arrest. The pattern of conduction depends on the regulation of heterogeneous gene expression by key transcription factors and transcriptional enhancers. Here, we assessed the genome-wide occupation of conduction system-regulating transcription factors TBX3, NKX2-5, and GATA4 and of enhancer-associated coactivator p300 in the mouse heart, uncovering cardiac enhancers throughout the genome. Many of the enhancers colocalized with ion channel genes repressed by TBX3, including the clustered sodium channel genes Scn5a, essential for cardiac function, and Scn10a. We identified 2 enhancers in the Scn5a/Scn10a locus, which were regulated by TBX3 and its family member and activator, TBX5, and are functionally conserved in humans. We also provided evidence that a SNP in the SCN10A enhancer associated with alterations in cardiac conduction patterns in humans disrupts TBX3/TBX5 binding and reduces the cardiac activity of the enhancer in vivo. Thus, the identification of key regulatory elements for cardiac conduction helps to explain how genetic variants in noncoding regulatory DNA sequences influence the regulation of cardiac conduction and the predisposition for cardiac arrhythmias. | Animals, Base Sequence, Binding Sites, Cell Line, Chromatin Immunoprecipitation, Consensus Sequence, Enhancer Elements, Genetic, Gene Expression Profiling, Gene Expression Regulation, Developmental, Genetic Loci, Genetic Variation, Heart Conduction System, Humans, Male, Mice, Mice, Transgenic, Myocardium, NAV1.5 Voltage-Gated Sodium Channel, NAV1.8 Voltage-Gated Sodium Channel, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Protein Binding, Sequence Analysis, DNA, Sodium Channels, T-Box Domain Proteins, Zebrafish | null |
22,706,304 | 2012-09-11 | 2021-10-21 | 1558-8238 | The Journal of clinical investigation | Chemosensitivity is controlled by p63 modification with ubiquitin-like protein ISG15. | Jeon Young Joo, Jo Mi Gyeong, Yoo Hee Min, Hong Se-Hoon, Park Jung-Mi, Ka Seung Hyeun, Oh Kyu Hee, Seol Jae Hong, Jung Yong Keun, Chung Chin Ha | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Antibiotics, Antineoplastic, Cytokines, Inhibitor of Apoptosis Proteins, Protein Isoforms, TP63 protein, human, Transcription Factors, Tumor Suppressor Proteins, Ubiquitins, ISG15 protein, human, Doxorubicin, CASP2 protein, human, Caspase 2, Cysteine Endopeptidases, Cisplatin, Camptothecin | IM | 22706304, 61762, 10.1172/JCI61762, PMC3386819, 16861923, 10791974, 15684817, 12446784, 14976209, 15908775, 16601749, 21335238, 20153823, 9573047, 21295273, 10416581, 21726810, 9733748, 16815975, 15988020, 15611636, 21427767, 16009940, 14599290, 15467455, 20951678, 21760596, 11854279, 12582176, 10227293, 10709110, 16352599, 16172118, 17188034, 17360634, 10453075, 15837625, 10801437, 12150997, 8654923, 12750249, 17581882, 14612504, 571963, 15485925, 18311128, 17036050, 19203584, 12193789, 10227294, 11891284, 19279217, 18806757, 17446929, 19609265, 17122775, 12107827, 11432830, 18413804, 8327486, 10945600, 15131269, 9506977, 12114540, 10805802, 18483491, 11279141, 12446779, 1373138, 15846104, 9018094, 11932750, 19074853, 12460989, 11157743, 19898465, 15917298, 16715076, 2440890, 16618808, 19652527, 15073321, 12086851, 19270716, 9774969, 9662378, 18566215, 9482881, 16714381, 16908849, 11462054, 11172034 | Identification of the cellular mechanisms that mediate cancer cell chemosensitivity is important for developing new cancer treatment strategies. Several chemotherapeutic drugs increase levels of the posttranslational modifier ISG15, which suggests that ISGylation could suppress oncogenesis. However, how ISGylation of specific target proteins controls tumorigenesis is unknown. Here, we identified proteins that are ISGylated in response to chemotherapy. Treatment of a human mammary epithelial cell line with doxorubicin resulted in ISGylation of the p53 family protein p63. An alternative splice variant of p63, ΔNp63α, suppressed the transactivity of other p53 family members, and its expression was abnormally elevated in various human epithelial tumors, suggestive of an oncogenic role for this variant. We showed that ISGylation played an essential role in the downregulation of ΔNp63α. Anticancer drugs, including doxorubicin, induced ΔNp63α ISGylation and caspase-2 activation, leading to cleavage of ISGylated ΔNp63α in the nucleus and subsequent release of its inhibitory domain to the cytoplasm. ISGylation ablated the ability of ΔNp63α to promote anchorage-independent cell growth and tumor formation in vivo as well to suppress the transactivities of proapoptotic p53 family members. These findings establish ISG15 as a tumor suppressor via its conjugation to ΔNp63α and provide a molecular rationale for therapeutic use of doxorubicin against ΔNp63α-mediated cancers. | Amino Acid Motifs, Animals, Antibiotics, Antineoplastic, Camptothecin, Caspase 2, Cell Line, Tumor, Cellular Senescence, Cisplatin, Cysteine Endopeptidases, Cytokines, Doxorubicin, Enzyme Activation, Humans, Inhibitor of Apoptosis Proteins, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasms, Protein Isoforms, Protein Processing, Post-Translational, Protein Structure, Tertiary, Proteolysis, Transcription Factors, Transcriptional Activation, Tumor Suppressor Proteins, Ubiquitins, Xenograft Model Antitumor Assays | null |
22,706,307 | 2012-09-11 | 2021-10-21 | 1558-8238 | The Journal of clinical investigation | Intravital 2-photon imaging of leukocyte trafficking in beating heart. | Li Wenjun, Nava Ruben G, Bribriesco Alejandro C, Zinselmeyer Bernd H, Spahn Jessica H, Gelman Andrew E, Krupnick Alexander S, Miller Mark J, Kreisel Daniel | eng | R01 AI077600 (NIAID NIH HHS, United States); R01 HL094601 (NHLBI NIH HHS, United States); AI077600 (NIAID NIH HHS, United States); 1R01HL094601 (NHLBI NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural | Recombinant Proteins, Green Fluorescent Proteins | IM | 22706307, 62970, 10.1172/JCI62970, PMC3386827, 20558756, 8946651, 11457896, 18843253, 12016203, 15811956, 10528208, 11756189, 2014549, 11045953, 6831665, 10435032, 8104198, 15611287, 19372476, 9843832, 2598440, 19268609, 11909820, 14962479, 21151136, 15187165, 20947763, 17116736, 18453558, 10527700, 17656447, 11376338, 10805752, 17673663, 19299693, 1357003, 8102030, 12415310, 17143330, 15504916, 20923880 | Two-photon intravital microscopy has substantially broadened our understanding of tissue- and organ-specific differences in the regulation of inflammatory responses. However, little is known about the dynamic regulation of leukocyte recruitment into inflamed heart tissue, largely due to technical difficulties inherent in imaging moving tissue. Here, we report a method for imaging beating murine hearts using intravital 2-photon microscopy. Using this method, we visualized neutrophil trafficking at baseline and during inflammation. Ischemia reperfusion injury induced by transplantation or transient coronary artery ligation led to recruitment of neutrophils to the heart, their extravasation from coronary veins, and infiltration of the myocardium where they formed large clusters. Grafting hearts containing mutant ICAM-1, a ligand important for neutrophil recruitment, reduced the crawling velocities of neutrophils within vessels, and markedly inhibited their extravasation. Similar impairment was seen with the inhibition of Mac-1, a receptor for ICAM-1. Blockade of LFA-1, another ICAM-1 receptor, prevented neutrophil adherence to endothelium and extravasation in heart grafts. As inflammatory responses in the heart are of great relevance to public health, this imaging approach holds promise for studying cardiac-specific mechanisms of leukocyte recruitment and identifying novel therapeutic targets for treating heart disease. | Animals, Cardiac Imaging Techniques, Coronary Vessels, Green Fluorescent Proteins, Heart Transplantation, Leukocyte Rolling, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Multiphoton, Myocardial Contraction, Myocardium, Neutrophil Infiltration, Quantum Dots, Recombinant Proteins, Time-Lapse Imaging | null |
22,706,306 | 2012-09-11 | 2022-03-09 | 1558-8238 | The Journal of clinical investigation | Fungal antioxidant pathways promote survival against neutrophils during infection. | Leal Sixto M, Vareechon Chairut, Cowden Susan, Cobb Brian A, Latgé Jean-Paul, Momany Michelle, Pearlman Eric | eng | P30 EY011373 (NEI NIH HHS, United States); R21 AI074846-02 (NIAID NIH HHS, United States); R01 EY018612 (NEI NIH HHS, United States); F31 EY019841 (NEI NIH HHS, United States); R21 AI074846 (NIAID NIH HHS, United States); T32 GM007250 (NIGMS NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | Antioxidants, CD18 Antigens, Fungal Proteins, Reactive Oxygen Species, Transcription Factors, Nitric Oxide, Thioredoxins, Peroxidase, Nitric Oxide Synthase Type II, Nos2 protein, mouse, Superoxide Dismutase, NADPH Oxidases | IM | 22706306, 63239, 10.1172/JCI63239, PMC3534057, 7917262, 12719478, 19342673, 20487287, 19026683, 17432932, 11325951, 15232472, 18608886, 3278004, 16304610, 16926355, 17601876, 16935335, 19840871, 21769097, 19296367, 18536919, 16799473, 20591493, 20461382, 17883327, 8690804, 12761140, 12521119, 20617171, 19512910, 20543597, 2165113, 14631389, 16710478, 21525931, 18645221, 12657718, 17850484, 15155643, 12517450, 17362452, 20840542, 21078850, 12761080, 17030582, 14614821, 17464852, 10421857, 21863237, 17631497, 7395957, 19811837, 19302044, 7719350, 11899431, 18199036, 18421291, 19032234, 17404093, 17921349, 20203215, 20467426, 8008340, 14557288, 21088683, 22224774, 9016870, 19594628, 16710324, 16575115, 18667168, 18648542, 8101543, 15039755, 17142767, 21828275, 20547942, 20971208, 18566426, 21257963, 10887140 | Filamentous fungi are a common cause of blindness and visual impairment worldwide. Using both murine model systems and in vitro human neutrophils, we found that NADPH oxidase produced by neutrophils was essential to control the growth of Aspergillus and Fusarium fungi in the cornea. We demonstrated that neutrophil oxidant production and antifungal activity are dependent on CD18, but not on the β-glucan receptor dectin-1. We used mutant A. fumigatus strains to show that the reactive oxygen species-sensing transcription factor Yap1, superoxide dismutases, and the Yap1-regulated thioredoxin antioxidant pathway are each required for protection against neutrophil-mediated oxidation of hyphae as well as optimal survival of fungal hyphae in vivo. We also demonstrated that thioredoxin inhibition using the anticancer drug PX-12 increased the sensitivity of fungal hyphae to both H2O2- and neutrophil-mediated killing in vitro. Additionally, topical application of PX-12 significantly enhanced neutrophil-mediated fungal killing in infected mouse corneas. Cumulatively, our data reveal critical host oxidative and fungal anti-oxidative mediators that regulate hyphal survival during infection. Further, these findings also indicate that targeting fungal anti-oxidative defenses via PX-12 may represent an efficacious strategy for treating fungal infections. | Animals, Antioxidants, Aspergillosis, Aspergillus flavus, Aspergillus fumigatus, CD18 Antigens, Cells, Cultured, Cornea, Enzyme Activation, Fungal Proteins, Fusariosis, Fusarium, Host-Pathogen Interactions, Humans, Keratitis, Mice, Mice, Inbred C57BL, Mice, Knockout, Microbial Viability, NADPH Oxidases, Neutrophil Infiltration, Neutrophils, Nitric Oxide, Nitric Oxide Synthase Type II, Oxidative Stress, Peroxidase, Reactive Oxygen Species, Superoxide Dismutase, Thioredoxins, Transcription Factors | null |
22,706,308 | 2012-09-11 | 2021-10-21 | 1558-8238 | The Journal of clinical investigation | NF-κB inhibition delays DNA damage-induced senescence and aging in mice. | Tilstra Jeremy S, Robinson Andria R, Wang Jin, Gregg Siobhán Q, Clauson Cheryl L, Reay Daniel P, Nasto Luigi A, St Croix Claudette M, Usas Arvydas, Vo Nam, Huard Johnny, Clemens Paula R, Stolz Donna B, Guttridge Denis C, Watkins Simon C, Garinis George A, Wang Yinsheng, Niedernhofer Laura J, Robbins Paul D | eng | P30 AG024827 (NIA NIH HHS, United States); ES016114 (NIEHS NIH HHS, United States); R21 AG033046 (NIA NIH HHS, United States); P30 CA047904 (NCI NIH HHS, United States); P30CA047904 (NCI NIH HHS, United States); F30 AG032816 (NIA NIH HHS, United States); AG033046 (NIA NIH HHS, United States); R21 AG033907 (NIA NIH HHS, United States); R01 AR051456 (NIAMS NIH HHS, United States); R01 ES016114 (NIEHS NIH HHS, United States); P20 CA103730 (NCI NIH HHS, United States); CA101864 (NCI NIH HHS, United States); R01 ES019873 (NIEHS NIH HHS, United States); CA103730 (NCI NIH HHS, United States); R01 CA101864 (NCI NIH HHS, United States); AG032816 (NIA NIH HHS, United States); AR051456 (NIAMS NIH HHS, United States); ES019873 (NIEHS NIH HHS, United States); AG024827 (NIA NIH HHS, United States); AG-NS-0303-05 (NIA NIH HHS, United States); AG033907 (NIA NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | Cdkn2a protein, mouse, Cyclin-Dependent Kinase Inhibitor p16, DNA-Binding Proteins, NBD peptide, mouse, Peptides, Rela protein, mouse, Transcription Factor RelA, I-kappa B Kinase, Endonucleases, Ercc1 protein, mouse | IM | 22706308, 45785, 10.1172/JCI45785, PMC3386805, 17116321, 15314504, 15716955, 16330259, 9343515, 21612988, 9143018, 12380689, 17072325, 20010931, 16447287, 12855956, 21321098, 18603018, 12882352, 19135883, 14698807, 15479644, 22048312, 22265401, 15265883, 19587680, 18541667, 18032778, 22215083, 18025231, 21187855, 15252035, 10318916, 3344216, 12164870, 22396894, 876356, 19135889, 17475882, 17072327, 1143025, 17183314, 4352451, 18000063, 19053174, 20973062, 4584835, 21953681, 18704162, 17690295, 18055696, 9853294, 21596054, 17522055, 17635154, 4696687, 17072322, 17086191, 16951143, 22953029, 8809053, 10409765, 8247224, 15734677, 11739381, 21323344, 21624467, 10075689, 21868666, 18574572, 10859214, 19797661, 15504972, 16724054, 17380205, 19303878, 14685699, 12610296, 14679201, 11899077, 18692159, 21886162, 16632109, 21118958, 16934229, 15164064, 18519641, 16439206, 18267068, 1915865, 18631391 | The accumulation of cellular damage, including DNA damage, is thought to contribute to aging-related degenerative changes, but how damage drives aging is unknown. XFE progeroid syndrome is a disease of accelerated aging caused by a defect in DNA repair. NF-κB, a transcription factor activated by cellular damage and stress, has increased activity with aging and aging-related chronic diseases. To determine whether NF-κB drives aging in response to the accumulation of spontaneous, endogenous DNA damage, we measured the activation of NF-κB in WT and progeroid model mice. As both WT and progeroid mice aged, NF-κB was activated stochastically in a variety of cell types. Genetic depletion of one allele of the p65 subunit of NF-κB or treatment with a pharmacological inhibitor of the NF-κB-activating kinase, IKK, delayed the age-related symptoms and pathologies of progeroid mice. Additionally, inhibition of NF-κB reduced oxidative DNA damage and stress and delayed cellular senescence. These results indicate that the mechanism by which DNA damage drives aging is due in part to NF-κB activation. IKK/NF-κB inhibitors are sufficient to attenuate this damage and could provide clinical benefit for degenerative changes associated with accelerated aging disorders and normal aging. | Aging, Animals, Cell Nucleus, Cells, Cultured, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, DNA Damage, DNA-Binding Proteins, Endonucleases, Gene Expression Regulation, Hepatocytes, I-kappa B Kinase, Mice, Mice, Transgenic, Oxidative Stress, Peptides, Phosphorylation, Progeria, Protein Binding, Signal Transduction, Transcription Factor RelA, Transcriptional Activation | null |
22,706,310 | 2013-01-03 | 2016-11-25 | 2042-650X | Food & function | Impact of crema on the aroma release and the in-mouth sensory perception of espresso coffee. | Barron D, Pineau N, Matthey-Doret W, Ali S, Sudre J, Germain J C, Kolodziejczyk E, Pollien P, Labbe D, Jarisch C, Dugas V, Hartmann C, Folmer B | eng | null | Journal Article | Coffee, Furans, Volatile Organic Compounds, 2-methylfuran | IM | 22706310, 10.1039/c2fo30046j | A set of six espresso coffees with different foam characteristics and similar above cup and in-mouth flavour sensory profiles was produced by combination of two varying parameters, the extraction pressure and the filtration of the coffee beverage. The coffees were subsequently evaluated in a comparative manner by a set of analytical (headspace, nose-space) and sensory (Temporal Dominance of Sensations) techniques. The presence of espresso crema in its standard quantity was demonstrated to be associated with the optimum release of pleasant high volatiles, both in the above cup headspace and in-mouth. On the other hand, the TDS study demonstrated that increasing amount of crema was associated with increasing roasted dominance along coffee consumption. Furthermore, a parallel was established between the roasted sensory dominance and the dominant release of 2-methylfuran in the nose-space. This was, however, an indirect link as 2-methylfuran was indeed a chemical marker of roasting but does not contribute to the roasted aroma. Lowering the standard amount of crema by filtration clearly decreased the release of pleasant high volatiles and the in-mouth roasted sensory dominance. On the other hand, increasing the usual crema volume by increasing the extraction pressure did not bring any added value concerning the above cup and in-mouth release of pleasant high volatiles. | Coffee, Food Technology, Furans, Mouth, Odorants, Taste, Taste Perception, Volatile Organic Compounds | null |
22,706,313 | 2012-11-05 | 2024-01-09 | 1546-1718 | Nature genetics | An efficient multi-locus mixed-model approach for genome-wide association studies in structured populations. | Segura Vincent, Vilhjálmsson Bjarni J, Platt Alexander, Korte Arthur, Seren Ümit, Long Quan, Nordborg Magnus | eng | P50 HG002790 (NHGRI NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | null | IM | 22706313, ng.2314, 10.1038/ng.2314, PMC3386481, NIHMS375806, 17676998, 20981092, 20018055, 20642809, 21407268, 21104890, 18654633, 20686565, 19060910, 22231484, 16862161, 8013918, 20208535, 20126254, 20336072, 20813880, 19763151, 17660554, 19060906, 21217756, 8224820, 20689309, 20208533, 12598158, 21085628, 10827107, 11719900, 11315092, 18385116, 19474203, 18252218, 15052271, 17238287, 16380716 | Population structure causes genome-wide linkage disequilibrium between unlinked loci, leading to statistical confounding in genome-wide association studies. Mixed models have been shown to handle the confounding effects of a diffuse background of large numbers of loci of small effect well, but they do not always account for loci of larger effect. Here we propose a multi-locus mixed model as a general method for mapping complex traits in structured populations. Simulations suggest that our method outperforms existing methods in terms of power as well as false discovery rate. We apply our method to human and Arabidopsis thaliana data, identifying new associations and evidence for allelic heterogeneity. We also show how a priori knowledge from an A. thaliana linkage mapping study can be integrated into our method using a Bayesian approach. Our implementation is computationally efficient, making the analysis of large data sets (n > 10,000) practicable. | Arabidopsis, Bayes Theorem, Chromosome Mapping, Genetic Loci, Genome, Human, Genome, Plant, Genome-Wide Association Study, Genotype, Humans, Linkage Disequilibrium, Models, Genetic, Molecular Dynamics Simulation, Polymorphism, Single Nucleotide, Population Groups, Quantitative Trait Loci | null |
22,706,312 | 2012-11-05 | 2024-06-10 | 1546-1718 | Nature genetics | Genome-wide efficient mixed-model analysis for association studies. | Zhou Xiang, Stephens Matthew | eng | R56 HG002585 (NHGRI NIH HHS, United States); HG02585 (NHGRI NIH HHS, United States); R01 HL092206 (NHLBI NIH HHS, United States); HL092206 (NHLBI NIH HHS, United States); R01 HG002585 (NHGRI NIH HHS, United States); 085475 (Wellcome Trust, United Kingdom) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | null | IM | 22706312, ng.2310, 10.1038/ng.2310, PMC3386377, NIHMS375372, 17660554, 21892150, 19543373, 20208533, 19057666, 11880950, 18791227, 20208535, 16380716, 20810919, 18949033, 20548291, 17554300, 18385116, 17384015, 20054062 | Linear mixed models have attracted considerable attention recently as a powerful and effective tool for accounting for population stratification and relatedness in genetic association tests. However, existing methods for exact computation of standard test statistics are computationally impractical for even moderate-sized genome-wide association studies. To address this issue, several approximate methods have been proposed. Here, we present an efficient exact method, which we refer to as genome-wide efficient mixed-model association (GEMMA), that makes approximations unnecessary in many contexts. This method is approximately n times faster than the widely used exact method known as efficient mixed-model association (EMMA), where n is the sample size, making exact genome-wide association analysis computationally practical for large numbers of individuals. | Computer Simulation, Genome, Human, Genome-Wide Association Study, Humans, Linear Models, Models, Genetic, Polymorphism, Single Nucleotide, Population Groups, Software | null |
22,706,314 | 2012-09-17 | 2022-01-29 | 1938-3673 | Journal of leukocyte biology | Slc11a1 (Nramp1) impairs growth of Salmonella enterica serovar typhimurium in macrophages via stimulation of lipocalin-2 expression. | Fritsche Gernot, Nairz Manfred, Libby Stephen J, Fang Ferric C, Weiss Günter | eng | TRP 188 (Austrian Science Fund FWF, Austria); R21 AI048622 (NIAID NIH HHS, United States); R01 AI077629 (NIAID NIH HHS, United States); R01 AI048622 (NIAID NIH HHS, United States); AI39557 (NIAID NIH HHS, United States); R01 AI039557 (NIAID NIH HHS, United States); AI77629 (NIAID NIH HHS, United States); R01 AI044486 (NIAID NIH HHS, United States); AI48622 (NIAID NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | Acute-Phase Proteins, Cation Transport Proteins, Lipocalin-2, Lipocalins, NF-kappa B, Oncogene Proteins, Reactive Nitrogen Species, Siderophores, natural resistance-associated macrophage protein 1, Lcn2 protein, mouse, Hydrogen Peroxide, Iron, Deferoxamine | IM | 22706314, jlb.1111554, 10.1189/jlb.1111554, PMC3395419, 12070036, 15744772, 20633248, 15642259, 19321419, 19700664, 20550936, 21601942, 11449359, 11058768, 15531878, 7959883, 11067873, 20121435, 19454351, 7650477, 12453412, 10024586, 11736990, 18991287, 19342674, 18086376, 9486992, 19500110, 8529105, 15322058, 10233755, 12750164, 11514223, 16446425, 18024118, 8635688, 10758409, 21274449, 17466014, 21256055, 12902503, 11903051, 20581821, 18194158, 19050270 | The expression of the cation transporter Nramp1 (Slc11a1) in late phagolysosomes confers resistance to infection with several intracellular pathogens, such as Salmonella enterica, in mice. The antimicrobial actions of Nramp1 are attributable, in part, to modulation of macrophage immune function and cellular iron metabolism--the latter affecting the availability of the essential nutrient iron for intraphagosomal bacteria. Here, we provide novel evidence that Nramp1 functionality increases the expression of the peptide Lcn2, which exerts its antimicrobial activity by scavenging iron-loaded bacterial siderophores and mediating iron efflux from macrophages. With the use of macrophage cell lines expressing functional or nonfunctional Nramp1, we found significantly elevated Lcn2 mRNA and protein levels in Nramp1-expressing cells. These resulted from Nramp1-mediated alterations in the production of ROS, which stimulated NF-κ B activity and subsequently, Lcn2 transcription. We observed that increased Lcn2 levels in primary Nramp1-positive macrophages resulted in a significant suppression of S. enterica serovar typhimurium growth. Stimulation of Lcn2 expression is a novel mechanism by which Nramp1 confers resistance against infection with the intracellular bacterium S. typhimurium. | Acute-Phase Proteins, Animals, Cation Transport Proteins, Cell Line, Deferoxamine, Hydrogen Peroxide, Immunity, Innate, Iron, Lipocalin-2, Lipocalins, Macrophages, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, NF-kappa B, Oncogene Proteins, Reactive Nitrogen Species, Salmonella Infections, Animal, Salmonella typhimurium, Siderophores | null |
22,706,315 | 2012-09-17 | 2021-10-21 | 1938-3673 | Journal of leukocyte biology | Eosinophil contamination of thioglycollate-elicited peritoneal macrophage cultures skews the functional readouts of in vitro assays. | Misharin Alexander V, Saber Rana, Perlman Harris | eng | AR054796 (NIAMS NIH HHS, United States); AR050250 (NIAMS NIH HHS, United States); P30 CA060553 (NCI NIH HHS, United States); R21 AI092490 (NIAID NIH HHS, United States); R01 AR050250 (NIAMS NIH HHS, United States); R01 AR054796 (NIAMS NIH HHS, United States); P01 HL108795 (NHLBI NIH HHS, United States); HL108795 (NHLBI NIH HHS, United States); CA060553 (NCI NIH HHS, United States); AI092490 (NIAID NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Validation Study | Thioglycolates | IM | 22706315, jlb.1111560, 10.1189/jlb.1111560, PMC3395415, 15383459, 14215638, 19016445, 6323464, 19347320, 20133793, 1378843, 19949323, 11207258, 9050940, 18370159, 13403399, 19710468, 15480321, 6366059, 3139757, 16226502, 7688028 | Thioglycollate-elicited peritoneal cells are a common source of macrophages for various in vitro assays, including stimulation with TLR ligands, cell signaling assays, phagocytosis, toxicology studies, and cytokine/chemokine production. The most common method for enrichment of cultured thioglycollate-elicited peritoneal cells is adherence. However, the presence of other cell types in freshly isolated and cultured thioglycollate-elicited peritoneal cells has not been examined. Here, we demonstrate that thioglycollate-elicited peritoneal cavity contains 55-60% nonmacrophage cells, and even after adherence, there are still 12-20% nonmacrophage cells remaining. Excluding macrophages, eosinophils are the major cell type in the freshly elicited cavity (30-40%). Eosinophils are also the major cell type contaminating in vitro cultures of thioglycollate-elicited peritoneal macrophages. Moreover, the contamination of macrophage cultures by eosinophils significantly diminishes activation of p38 MAPK and the serine threonine kinase Akt and production of proinflammatory cytokines in response to LPS stimulation. Taken together, these data suggest that thioglycollate-elicited peritoneal cells are far more heterogeneous than reported previously. Further, a failure to remove contaminating eosinophils may greatly affect the interpretation of results obtained with cultured thioglycollate-elicited macrophages. Thus, our data indicate that future studies intent on accurately assessing cultured macrophage phenotype and activation require depletion of all cocontaminating cells, especially eosinophils. | Animals, Cell Separation, Cells, Cultured, Eosinophils, Flow Cytometry, In Vitro Techniques, Macrophages, Peritoneal, Mice, Mice, Inbred C57BL, Thioglycolates | null |
22,706,316 | 2012-10-31 | 2022-03-11 | 1938-3673 | Journal of leukocyte biology | Insulin-containing lipogenic stimuli suppress mast cell degranulation potential and up-regulate lipid body biogenesis and eicosanoid secretion in a PPARγ-independent manner. | Greineisen William E, Shimoda Lori M N, Maaetoft-Udsen Kristina, Turner Helen | eng | P20 MD006084 (NIMHD NIH HHS, United States); P20 RR018727 (NCRR NIH HHS, United States); P20MD06084 (NIMHD NIH HHS, United States); P20RR018727 (NCRR NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S. | Eicosanoids, Insulin, Lipids, PPAR gamma | IM | 22706316, jlb.0811406, 10.1189/jlb.0811406, PMC3427608, 1913334, 188043, 2404155, 8761489, 7679699, 15459132, 11328886, 12876413, 7881676, 9294145, 17046573, 6436254, 15337753, 19669619, 16979555, 18771558, 19965608, 20303960, 19335553, 17395498, 10423409, 15970660, 12754288, 19699172, 19041421, 16945418, 16493068, 20583030, 18224286, 8346866, 1316915, 541350, 2329799, 18339853, 18518822, 18394132, 20018750, 11479724, 19633655, 19484665, 6349447, 15741656, 16155260, 3988795, 21430261, 16962104, 19118639, 7679429, 19561094, 20498670, 4448705, 6190761, 11035823, 10096882, 20004975, 21245029, 17135363, 19733624, 8753842, 19573621, 165899, 7613146, 6315820, 18505743, 15962110, 11274187 | Lipid bodies are most studied in adipocytes, where the lipogenic action of insulin initiates their formation. Here, we test the hypothesis that insulin may regulate lipid body content in mast cells and hence, modify their proinflammatory potential. Our data show that insulin causes lipid body accumulation in RBL2H3 and BMMCs. Lipid body accumulation in mast cells is associated with enhanced levels of leukotriene-synthesizing enzymes (LTC4S and 5-LO). Increased basal and antigen-stimulated release of LTC4 is observed in insulin-treated mast cells. Concomitantly, the insulin-containing lipogenic stimulus induces a phenotypic change in mast cells, where this enhancement in leukotriene levels is accompanied by a marked down-regulation in secretory granule content and release in response to stimulus. Mast cells exposed to insulin exhibit altered scatter and fluorescence properties, accumulating in a SSC(lo)FSC(hi) population that exhibits decreased BS staining and degranulation responses and is enriched in NR-positive lipid bodies and eicosanoid synthesis enzymes. Lipid body accumulation in mast cells is mechanistically distinct from the process in adipocytes; for example, it is independent of PPARγ up-regulation and does not involve significant accumulation of conjugated glycerides. Thus, chronic exposure to metabolic stimuli, such as insulin, may be a determinant of the proinflammatory potential of the mast cell. | Animals, Blotting, Western, Cell Degranulation, Eicosanoids, Flow Cytometry, Immunohistochemistry, Inclusion Bodies, Insulin, Lipids, Mast Cells, Mice, PPAR gamma, Real-Time Polymerase Chain Reaction, Up-Regulation | null |
22,706,317 | 2013-01-29 | 2022-03-16 | 1420-908X | Inflammation research : official journal of the European Histamine Research Society ... [et al.] | Pro-inflammatory cytokine interleukin-1β promotes the development of intestinal stem cells. | Wang Lei, Liu Ziyan, Li Yijing, Pappan Loretta, Galliher-Beckley Amy, Shi Jishu | eng | P20-RR017686 (NCRR NIH HHS, United States); R21 AI085416 (NIAID NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | Bmi1 protein, rat, Interleukin-1beta, Lgr5 protein, rat, Nanog Homeobox Protein, Nanog protein, rat, Proto-Oncogene Proteins c-myb, RNA, Messenger, Receptors, G-Protein-Coupled, Transcription Factors, beta Catenin, Polycomb Repressive Complex 1 | IM | 22706317, 10.1007/s00011-012-0501-3, 11808612, 19520911, 21677748, 15886888, 17617617, 19563763, 15309885, 103096, 18054544, 19197002, 8899101, 19128792, 21927002, 12756227, 19500347, 12040179, 18977329, 19185844, 22215058, 19701245, 19092804, 17122771, 19934041, 6273638, 12106600, 11241255, 18536716, 19185845, 19218090, 15790842, 22170051, 22330721, 20683682 | We investigated the effect of IL-1β on the development of intestinal epithelial stem cells. | Animals, Cell Line, Cell Proliferation, Interleukin-1beta, Intestines, Nanog Homeobox Protein, Polycomb Repressive Complex 1, Proto-Oncogene Proteins c-myb, RNA, Messenger, Rats, Receptors, G-Protein-Coupled, Stem Cells, Transcription Factors, beta Catenin | null |
22,706,318 | 2013-01-29 | 2021-10-21 | 1420-908X | Inflammation research : official journal of the European Histamine Research Society ... [et al.] | High glucose increases nitric oxide generation in lipopolysaccharide-activated macrophages by enhancing activity of protein kinase C-α/δ and NF-κB. | Hua Kuo-Feng, Wang Szu-Hsuan, Dong Wei-Chih, Lin Chai-Yi, Ho Chen-Lung, Wu Tzu-Hua | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Cytokines, Lipopolysaccharides, NF-kappa B, Nitric Oxide, Nitric Oxide Synthase Type II, Nos2 protein, mouse, Protein Kinase C-alpha, Protein Kinase C-delta, Mitogen-Activated Protein Kinases, Glucose | IM | 22706318, 10.1007/s00011-012-0503-1, 18180316, 16455783, 9452447, 12716761, 17426109, 9236411, 12606524, 10983873, 18650365, 11997234, 15377563, 17167474, 12410803, 9248714, 16899235, 16889991, 7808095, 12107724, 18824162, 10837498, 17956941, 15854663, 20839800, 17202326, 9916130, 18673007, 7531975, 14988266, 8315943, 10900231, 7506873, 9042381 | Although several mechanisms by which hyperglycemia modulate inflammation have been proposed, it remains unclear how hyperglycemia regulates inflammation induced by lipopolysaccharide (LPS). | Animals, Cell Line, Cytokines, Glucose, HEK293 Cells, Humans, Inflammation, Lipopolysaccharides, Macrophages, Mice, Mitogen-Activated Protein Kinases, NF-kappa B, Nitric Oxide, Nitric Oxide Synthase Type II, Protein Kinase C-alpha, Protein Kinase C-delta | null |
22,706,319 | 2013-01-29 | 2021-10-21 | 1420-908X | Inflammation research : official journal of the European Histamine Research Society ... [et al.] | Modulation of heat shock proteins during macrophage differentiation. | Fagone Paolo, Di Rosa Michelino, Palumbo Maria, De Gregorio Corinne, Nicoletti Ferdinando, Malaguarnera Lucia | eng | null | Journal Article | Heat-Shock Proteins, RNA, Messenger | IM | 22706319, 10.1007/s00011-012-0506-y, 9655479, 3862119, 19542450, 11399049, 17675458, 3346328, 12697304, 20410505, 17186576, 9880236, 19164900, 9003468, 11861608, 19593530, 11584270, 2442598, 8348742, 6684733, 2419474, 17167422 | To evaluate the heat shock protein (HSP) variation during the differentiation and polarization of human macrophages. | Cell Differentiation, Cells, Cultured, Gene Expression Profiling, Gene Expression Regulation, Heat-Shock Proteins, Humans, Macrophages, Monocytes, RNA, Messenger | null |
22,706,320 | 2013-01-29 | 2021-10-21 | 1420-908X | Inflammation research : official journal of the European Histamine Research Society ... [et al.] | Exhaled breath condensate pH in patients with cystic fibrosis. | Antus Balazs, Barta Imre, Csiszer Eszter, Kelemen Krisztina | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Nitric Oxide | IM | 22706320, 10.1007/s00011-012-0508-9, 18634869, 16055882, 16055875, 15618579, 10712309, 17079255, 19670404, 12016097, 11254823, 14680074, 16135737, 15189915, 9927373, 19703285, 17890073, 17880760, 21289593, 15223872, 22106016, 15817806, 20081096, 19233745, 15684290, 9988124, 20656939, 18249106, 18368450, 12665124, 12403872, 18312532, 15499663, 18042977, 15618578, 9551733 | Exhaled breath condensate (EBC) pH has been proposed as a useful, non-invasive marker of airway inflammation in pulmonary diseases. In this study we tested whether cystic fibrosis (CF) is associated with acidification of EBC, when pH is assessed by the CO(2) gas standardization method. | Adult, Breath Tests, Case-Control Studies, Cystic Fibrosis, Exhalation, Female, Humans, Hydrogen-Ion Concentration, Male, Nitric Oxide, Respiratory Function Tests, Sputum | null |
22,706,321 | 2012-09-11 | 2018-12-01 | 1534-6080 | Transplantation | Tertiary hyperparathyroidism in kidney transplant recipients: characteristics of patients selected for different treatment strategies. | Yang Rachel L, Freeman Kate, Reinke Caroline E, Fraker Douglas L, Karakousis Giorgos C, Kelz Rachel R, Doyle Alden M | eng | null | Journal Article | Naphthalenes, Creatinine, Calcium, Cinacalcet | IM | 22706321, 10.1097/TP.0b013e3182530699 | Several treatment options exist for kidney transplant patients with tertiary hyperparathyroidism. However, the decision to endorse observation (OBS), medical therapy, or parathyroidectomy (PTX) remains controversial. | Adult, Aged, Calcium, Cinacalcet, Cohort Studies, Creatinine, Female, Humans, Hyperparathyroidism, Kidney Transplantation, Male, Middle Aged, Naphthalenes, Parathyroidectomy, Retrospective Studies | null |
22,706,323 | 2012-11-27 | 2018-12-01 | 1618-2650 | Analytical and bioanalytical chemistry | Letter to the editor regarding "Lactose does not interfere with the analysis of sialic acids as their 1,2-diamino-4,5-methylenedioxybenzene derivatives". | Martín Maria J, Ramirez Maria, Vázquez Enrique, Rueda Ricardo | eng | null | Letter, Comment | Phenylenediamines, Sialic Acids, Lactose | IM | 22706323, 10.1007/s00216-012-6154-9 | null | Lactose, Phenylenediamines, Sialic Acids | null |
22,706,322 | 2012-09-11 | 2018-12-17 | 1534-6080 | Transplantation | Caspase inhibitor IDN6556 facilitates marginal mass islet engraftment in a porcine islet autotransplant model. | McCall Michael D, Maciver Allison M, Kin Tatsuya, Emamaullee Juliet, Pawlick Rena, Edgar Ryan, Shapiro A M James | eng | null | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | 3-(2-(2-tert-butylphenylaminooxalyl)aminopropionylamino)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid, Blood Glucose, Caspase Inhibitors, Insulin, Pentanoic Acids, Protease Inhibitors | IM | 22706322, 10.1097/TP.0b013e318257745d | Large numbers of islets are lost in the early phase after clinical islet transplantation, through apoptosis, necrosis, or innate inflammatory injury. We previously demonstrated the efficacy of a series of caspase inhibitors in mouse models on islet engraftment through reduction in early posttransplant apoptosis. We studied IDN6556, a caspase inhibitor with a first-pass effect, in a large animal (pig) intraportal marginal mass islet autotransplant model. | Animals, Blood Glucose, Caspase Inhibitors, Female, Insulin, Insulin Secretion, Islets of Langerhans Transplantation, Models, Animal, Pentanoic Acids, Protease Inhibitors, Swine, Swine, Miniature, Transplantation, Autologous | null |
22,706,325 | 2012-11-19 | 2016-05-12 | 1618-2650 | Analytical and bioanalytical chemistry | NMR metabolomics for assessment of exercise effects with mouse biofluids. | Le Moyec Laurence, Mille-Hamard Laurence, Triba Mohamed N, Breuneval Carole, Petot Hélène, Billat Véronique L | eng | null | Journal Article | null | IM | 22706325, 10.1007/s00216-012-6165-6 | Exercise modulates the metabolome in urine or blood as demonstrated previously for humans and animal models. Using nuclear magnetic resonance (NMR) metabolomics, the present study compares the metabolic consequences of an exhaustive exercise at peak velocity (Vp) and at critical velocity (Vc) on mice. Since small-volume samples (blood and urine) were collected, dilution was necessary to acquire NMR spectra. Consequently, specific processing methods were applied before statistical analysis. According to the type of exercise (control group, Vp group and Vc group), 26 male mice were divided into three groups. Mice were sacrificed 2 h after the end of exercise, and urine and blood samples were drawn from each mouse. Proton NMR spectra were acquired with urine and deproteinized blood. The NMR data were aligned with the icoshift method and normalised using the probabilistic quotient method. Finally, data were analysed with the orthogonal projection of latent-structure analysis. The spectra obtained with deproteinized blood can neither discriminate the control mice from exercised mice nor discriminate according to the duration of the exercise. With urine samples, a significant statistical model can be estimated when comparing the control mice to both groups, Vc and Vp. The best model is obtained according to the exercise duration with all mice. Taking into account the spectral regions having the highest correlations, the discriminant metabolites are allantoin, inosine and branched-chain amino acids. In conclusion, metabolomic profiles assessed with NMR are highly dependent on the exercise. These results show that urine samples are more informative than blood samples and that the duration of the exercise is a more important parameter to influence the metabolomic status than the exercise velocity. | Animals, Body Fluids, Magnetic Resonance Spectroscopy, Metabolomics, Mice, Physical Conditioning, Animal | null |
22,706,326 | 2012-11-19 | 2016-05-12 | 1618-2650 | Analytical and bioanalytical chemistry | Improved spatial resolution in the imaging of biological tissue using desorption electrospray ionization. | Campbell Dahlia I, Ferreira Christina R, Eberlin Livia S, Cooks R Graham | eng | null | Journal Article, Research Support, U.S. Gov't, Non-P.H.S. | null | IM | 22706326, 10.1007/s00216-012-6173-6 | Desorption electrospray ionization imaging allows biomarker discovery and disease diagnosis through chemical characterization of biological samples in their native environment. Optimization of experimental parameters including emitter capillary size, solvent composition, solvent flow rate, mass spectrometry scan-rate and step-size is shown here to improve the resolution available in the study of biological tissue from 180 μm to about 35 μm using an unmodified commercial mass spectrometer. Mouse brain tissue was used to optimize and measure resolution based on known morphological features and their known relationships to major phospholipid components. Features of approximately 35 μm were resolved and correlations drawn between features in grey matter (principally PS (18:0/22:6), m/z 834) and in white matter (principally ST (24:1), m/z 888). The improved spatial resolution allowed characterization of the temporal changes in lipid profiles occurring within mouse ovaries during the ovulatory cycle. An increase in the production of phosphatidylinositol (PI 38:4) m/z 885 and associated fatty acids such as arachidonic acid (FA 20:4) m/z 303 and adrenic acid (FA 22:4) m/z 331was seen with the postovulatory formation of the corpus luteum. | Animals, Brain, Female, Lipid Metabolism, Mice, Ovary, Spectrometry, Mass, Electrospray Ionization | null |
22,706,328 | 2013-02-20 | 2012-08-14 | 1364-5528 | The Analyst | Characterization of microstructured fibre emitters: in pursuit of improved nano electrospray ionization performance. | Wu Xinyun, Oleschuk Richard D, Cann Natalie M | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Carbohydrates | IM | 22706328, 10.1039/c2an35249d | Full-dimensional computational fluid dynamics (CFD) simulations are presented for nano electrospray ionization (ESI) with various emitter designs. Our CFD electrohydrodynamic simulations are based on the Taylor-Melcher leaky-dielectric model, and the volume of fluid technique for tracking the fast-changing liquid-gas interface. The numerical method is first validated for a conventional 20 μm inner diameter capillary emitter. The impact of ESI voltage, flow rate, emitter tapering, surface hydrophobicity, and fluid conductivity on the nano-ESI behavior are thoroughly investigated and compared with experiments. Multi-electrospray is further simulated with 2-hole and 3-hole emitters with the latter having a linear or triangular hole arrangement. The simulations predict multi-electrospray behavior in good agreement with laboratory observations. | Carbohydrates, Hydrodynamics, Spectrometry, Mass, Electrospray Ionization | null |
22,706,329 | 2012-10-24 | 2012-07-03 | 1477-9234 | Dalton transactions (Cambridge, England : 2003) | Structure, photophysical properties and computational study of a highly luminescent mixed-metal platinum(II)-silver(I) system. Potential building blocks for emissive supramolecular structures. | Lam Elizabeth Suk Hang, Tam Anthony Yiu-Yan, Lam Wai Han, Wong Keith Man-Chung, Zhu Nianyong, Yam Vivian Wing-Wah | eng | null | Journal Article | null | null | 22706329, 10.1039/c2dt30598d | A luminescent cyclometalated platinum(II) complex has been shown to sandwich a silver ion, which demonstrates intense luminescence with appreciable photoluminescence quantum yield. Computational studies have been performed to provide insights into the nature of the photophysical properties. | null | null |
22,706,327 | 2012-10-15 | 2022-04-08 | 1535-7228 | The American journal of psychiatry | A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. | Gray Kevin M, Carpenter Matthew J, Baker Nathaniel L, DeSantis Stacia M, Kryway Elisabeth, Hartwell Karen J, McRae-Clark Aimee L, Brady Kathleen T | eng | K23 DA020482 (NIDA NIH HHS, United States); R01 DA026777 (NIDA NIH HHS, United States); UL1 TR000062 (NCATS NIH HHS, United States); UL1 RR029882 (NCRR NIH HHS, United States); K23DA020482 (NIDA NIH HHS, United States); UL1RR029882 (NCRR NIH HHS, United States); R01DA026777 (NIDA NIH HHS, United States) | Journal Article, Randomized Controlled Trial, Research Support, American Recovery and Reinvestment Act, Research Support, N.I.H., Extramural | Cannabinoids, Excitatory Amino Acid Antagonists, Acetylcysteine | IM | 22706327, 1184217, 10.1176/appi.ajp.2012.12010055, PMC3410961, NIHMS374807, 3719049, 21160464, 18444060, 20331933, 11252586, 19103434, 17032099, 3395719, 12483769, 20163391, 17113207, 20934835, 15501373, 21303920, 9881538, 21519339, 21521427, 12069695, 19630711, 19717250, 21173236, 19136971, 21536062, 15501372, 19348837, 17606664, 15866314, 15381886, 18675832, 12492757, 2081237, 21118657, 22470287, 17613964, 21310551, 17719565 | Preclinical findings suggest that the over-the-counter supplement N-acetylcysteine (NAC), via glutamate modulation in the nucleus accumbens, holds promise as a pharmacotherapy for substance dependence. The authors investigated NAC as a novel cannabis cessation treatment in adolescents, a vulnerable group for whom existing treatments have shown limited efficacy. | Acetylcysteine, Adolescent, Cannabinoids, Counseling, Double-Blind Method, Excitatory Amino Acid Antagonists, Female, Humans, Male, Marijuana Abuse, Treatment Outcome, Young Adult | null |
22,706,331 | 2012-11-16 | 2012-07-20 | 1463-9084 | Physical chemistry chemical physics : PCCP | Charge transport in poly-imidazole membranes: a fresh appraisal of the Grotthuss mechanism. | Mangiatordi Giuseppe Felice, Butera Valeria, Russo Nino, Laage Damien, Adamo Carlo | eng | null | Journal Article | null | null | 22706331, 10.1039/c2cp23727j | A detailed theoretical investigation of the charge transport mechanism in poly(4-vinyl-imidazole) (P4VI), the parent polymer of a series of N-heterocyclic-based membranes used as an electrolyte in proton exchange membrane fuel cells, is presented. In particular, Density Functional Theory (DFT) results obtained for small model systems (protonated imidazole dimers and trimers) suggest that the commonly accepted conduction mechanism, based on a sequential proton transfer between imidazole moieties, could be impeded by the geometrical constraints imposed by the polymeric backbone. Indeed only one kind of proton transfer reaction is energetically allowed between adjacent imidazoles, so that a rotation of the protonated imidazole is required for a second proton transfer. Molecular dynamics simulations on a larger model (15 oligomers with an excess proton) show that the rotation of the imidazole carrying the excess proton is a soft large amplitude motion. These results allow us to propose a new proton conduction mechanism in P4VI, where a frustrated rotation of the protonated imidazole before each proton transfer reaction represents the rate-limiting step. Furthermore, in contrast with the Grotthuss proton transport mechanism in water, our results indicate that here it is the same proton which could be successively transferred. From a chemical point of view, these new insights into the mechanism are relevant for a rational design of modified azole-based systems for Proton Exchange Membrane Fuel Cells. | null | null |
22,706,332 | 2013-04-03 | 2022-03-11 | 1545-7214 | The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry | Prediction of incident dementia: impact of impairment in instrumental activities of daily living and mild cognitive impairment-results from the German study on ageing, cognition, and dementia in primary care patients. | Luck Tobias, Luppa Melanie, Wiese Birgit, Maier Wolfgang, van den Bussche Hendrik, Eisele Marion, Jessen Frank, Weeg Dagmar, Weyerer Siegfried, Pentzek Michael, Leicht Hanna, Koehler Mirjam, Tebarth Franziska, Olbrich Julia, Eifflaender-Gorfer Sandra, Fuchs Angela, Koenig Hans-Helmut, Riedel-Heller Steffi G | eng | null | Journal Article, Research Support, Non-U.S. Gov't | null | IM | 22706332, 10.1097/JGP.0b013e31825c09bc, S1064-7481(12)62026-0 | There is an increasing call for a stronger consideration of impairment in instrumental activities of daily living (IADL) in the diagnostic criteria of Mild Cognitive Impairment (MCI) to improve the prediction of dementia. Thus, the aim of the study was to determine the predictive capability of MCI and IADL impairment for incident dementia. | Activities of Daily Living, Aged, Aged, 80 and over, Alzheimer Disease, Cognitive Dysfunction, Dementia, Dementia, Multi-Infarct, Female, General Practice, Germany, Health Surveys, Humans, Male, Neuropsychological Tests, Predictive Value of Tests, Primary Health Care, Psychometrics | null |
22,706,330 | 2014-02-03 | 2021-10-21 | 1522-9629 | Pulmonary pharmacology & therapeutics | Emerging roles for cholesterol and lipoproteins in lung disease. | Gowdy Kymberly M, Fessler Michael B | eng | Z01 ES102005 (Intramural NIH HHS, United States); Z01 ES102005-02 (Intramural NIH HHS, United States); Z99 ES999999 (Intramural NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural | Anticholesteremic Agents, Cholesterol | IM | 22706330, S1094-5539(12)00077-6, 10.1016/j.pupt.2012.06.002, PMC3466369, NIHMS387313, 20870757, 15591471, 11574755, 18322240, 18954848, 18310229, 17426203, 18423196, 17050558, 18501625, 9316499, 22130116, 21484785, 21115733, 18831711, 16877692, 19235776, 11499696, 20175894, 19920234, 7401938, 20622028, 21473764, 17984165, 17673694, 19302040, 20084838, 16042797, 18757458, 20668705, 15302729, 20498409, 17848583, 18227397, 21864337, 15650559, 15665042, 20110577, 17316144, 22539789, 18505807, 8305422, 3024539, 15677772, 17405904, 18292555, 20659133, 20581153, 12615629, 20920765, 16781387, 19608720, 15316134, 16809409, 21465237, 19897745, 17592214, 20428172, 17332894, 11001066, 19436111, 21198438, 21131532, 17141851, 16002570, 20168318, 19183945, 17960026, 15976321, 10428977, 18366117, 2010686, 17060337, 15533864, 19139765, 21128938, 15096493, 17959631, 19717840, 18852364, 12196340, 17908708, 20861293, 16055479, 18955636, 22096372, 18292583, 19800678, 20395559, 12860890, 16574162, 18344414, 6892941, 20463180, 17766241, 15821229, 14978092, 10515593, 15826936, 18422598, 22089718 | Dyslipidemia, the condition of elevated serum triglycerides, elevated low-density lipoprotein cholesterol, and/or low high-density lipoprotein cholesterol, is a public health problem of growing concern. Dyslipidemia clusters with other disorders of the metabolic syndrome that together influence, and may derive from, chronic inflammation. While best recognized as a risk factor for atherosclerotic cardiovascular disease, lipid dysregulation has recently been shown to influence a variety of disease processes in several organ systems. This review highlights our current understanding of the role of cholesterol and its homeostatic trafficking in pulmonary physiology and pathophysiology. Gene-targeted mice deficient in regulatory proteins that govern reverse cholesterol transport (e.g., ATP Binding Cassette transporter G1, apolipoprotein E) have recently been shown to have abnormal lung physiology, including dysregulated pulmonary innate and adaptive immune responses to the environment. It has also recently been shown that diet-induced dyslipidemia alters trafficking of immune cells to the lung in a manner that may have important implications for the pathogenesis of acute lung injury, asthma, pneumonia, and other lung disorders. Conversely, cholesterol-targeting pharmacologic agents, such as statins, apolipoprotein mimetic peptides, and Liver X Receptor agonists, have shown early promise in the treatment of several lung disorders. An improved understanding of the precise molecular mechanisms by which cholesterol and its trafficking modify pulmonary immunity will be required before the full implications of dyslipidemia as a lung disease modifier, and the full potential of lipid-targeting agents as pulmonary therapeutics, can be realized. | Adaptive Immunity, Animals, Anticholesteremic Agents, Cholesterol, Disease Models, Animal, Dyslipidemias, Humans, Immunity, Innate, Inflammation, Lung Diseases, Mice, Risk Factors | null |
22,706,334 | 2012-11-08 | 2012-06-28 | 1757-9708 | Integrative biology : quantitative biosciences from nano to macro | Efficiently mining protein interaction dependencies from large text corpora. | Köster Johannes, Zamir Eli, Rahmann Sven | eng | null | Journal Article | Integrins, Proteins | IM | 22706334, 10.1039/c2ib00126h | Biochemical research has yielded an extensive amount of information about dependencies between protein interactions, as generated by allosteric regulations, steric hindrance and other mechanisms. Collectively, this information is valuable for understanding large intracellular protein networks. However, this information is sparsely distributed among millions of publications and documented as freely styled text meant for manual reading. Here we develop a computational approach for extracting information about interaction dependencies from large numbers of publications. First, keyword-based tokenization reduces full papers to short strings, facilitating an efficient search for patterns that are likely to indicate descriptions of interaction dependencies. Sentences that match such patterns are extracted, thereby reducing the amount of text to be read by human curators. Application of this approach to the integrin adhesome network extracted from 59,933 papers 208 short statements, close to half of which indeed describe interaction dependencies. We visualize the obtained hypernetwork of dependencies and illustrate that these dependencies confine the feasible mechanisms of adhesion sites assembly and generate testable hypotheses about their switchability. | Algorithms, Allosteric Site, Cell Adhesion, Computational Biology, Data Mining, Humans, Information Storage and Retrieval, Integrins, Models, Biological, Predictive Value of Tests, Protein Interaction Mapping, Proteins, Reproducibility of Results, Software, Systems Biology | null |
22,706,336 | 2014-04-03 | 2022-12-07 | 1536-481X | Journal of glaucoma | Intraocular pressure-reducing effects of latanoprost versus timolol in chinese patients with chronic angle-closure glaucoma. | Zhao Jialiang, Ge Jian, Sun Xinhuai, Wang Ningli | eng | null | Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't | Antihypertensive Agents, Prostaglandins F, Synthetic, Latanoprost, Timolol | IM | 22706336, 10.1097/IJG.0b013e31825af33e | To compare the efficacy and safety of latanoprost and timolol in Chinese patients with chronic angle-closure glaucoma (CACG), who had undergone laser or surgical peripheral iridotomy but who continued to experience elevated intraocular pressure (IOP) levels. | Adolescent, Adult, Aged, Antihypertensive Agents, Asian People, China, Chronic Disease, Female, Glaucoma, Angle-Closure, Humans, Intraocular Pressure, Latanoprost, Male, Middle Aged, Prostaglandins F, Synthetic, Timolol, Treatment Outcome, Young Adult | null |
22,706,337 | 2014-06-11 | 2025-01-03 | 1536-481X | Journal of glaucoma | Red laser cyclophotocoagulation in the treatment of secondary glaucoma in eyes with uveal melanoma. | Piirtola Anni, Puska Päivi, Kivelä Tero | eng | null | Journal Article | null | IM | 22706337, 10.1097/IJG.0b013e31825c0fb7 | To evaluate retrospectively the usefulness of the red diode and krypton laser for transscleral contact cyclophotocoagulation (CPC) in the treatment of secondary glaucoma in eyes with uveal melanoma. | Adult, Aged, Aged, 80 and over, Brachytherapy, Ciliary Body, Female, Glaucoma, Humans, Intraocular Pressure, Laser Coagulation, Lasers, Excimer, Lasers, Semiconductor, Male, Melanoma, Middle Aged, Retrospective Studies, Tonometry, Ocular, Treatment Outcome, Uveal Neoplasms, Visual Acuity, Uveal Melanoma | null |
22,706,338 | 2014-06-11 | 2022-04-09 | 1536-481X | Journal of glaucoma | Impaired saccadic eye movement in primary open-angle glaucoma. | Lamirel Cédric, Milea Dan, Cochereau Isabelle, Duong Minh-Hanh, Lorenceau Jean | eng | null | Journal Article, Research Support, Non-U.S. Gov't | null | IM | 22706338, 10.1097/IJG.0b013e31825c10dc | Our study aimed at investigating the extent to which saccadic eye movements are disrupted in patients with primary open-angle glaucoma (POAG). This approach followed upon the discovery of differences in the eye-movement behavior of POAG patients during the exploration of complex visual scenes. | Adult, Aged, Eye Movement Measurements, Female, Glaucoma, Open-Angle, Humans, Male, Middle Aged, Ocular Motility Disorders, Saccades, Scotoma, Visual Field Tests, Visual Fields | null |
22,706,339 | 2012-10-08 | 2022-03-30 | 1529-2916 | Nature immunology | Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. | Holm Christian K, Jensen Søren B, Jakobsen Martin R, Cheshenko Natalia, Horan Kristy A, Moeller Hanne B, Gonzalez-Dosal Regina, Rasmussen Simon B, Christensen Maria H, Yarovinsky Timur O, Rixon Frazer J, Herold Betsy C, Fitzgerald Katherine A, Paludan Søren R | eng | R01 AI061679 (NIAID NIH HHS, United States); R56 AI061679 (NIAID NIH HHS, United States); R37 AI067497 (NIAID NIH HHS, United States); R01 AI067497 (NIAID NIH HHS, United States); MC_U130115834 (Medical Research Council, United Kingdom); R56 AI067497 (NIAID NIH HHS, United States); AI067497 (NIAID NIH HHS, United States); AI061679 (NIAID NIH HHS, United States); MC_UU_12014/6 (Medical Research Council, United Kingdom); R01 AI083713 (NIAID NIH HHS, United States); AI083713 (NIAID NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | Chemokine CXCL10, Cxcl10 protein, mouse, Interferon Type I, Membrane Glycoproteins, Membrane Proteins, Myd88 protein, mouse, Myeloid Differentiation Factor 88, STING1 protein, human, Sting1 protein, mouse, Tlr7 protein, mouse, Tlr9 protein, mouse, Toll-Like Receptor 7, Toll-Like Receptor 9 | IM | 22706339, ni.2350, 10.1038/ni.2350, PMC3411909, NIHMS379462, 18575461, 21949653, 20890285, 20630948, 20826748, 18971278, 21820332, 19177264, 15308695, 21892174, 19158675, 19139171, 17898060, 21267015, 19132916, 18389479, 9499060, 1848601, 2700931, 21616434, 14568989, 20184308, 21813605, 18769720, 20538506, 21376176, 19776740, 21345957, 18724357, 7609061, 20159618, 20810749 | The innate immune system senses infection by detecting either evolutionarily conserved molecules essential for the survival of microbes or the abnormal location of molecules. Here we demonstrate the existence of a previously unknown innate detection mechanism induced by fusion between viral envelopes and target cells. Virus-cell fusion specifically stimulated a type I interferon response with expression of interferon-stimulated genes, in vivo recruitment of leukocytes and potentiation of signaling via Toll-like receptor 7 (TLR7) and TLR9. The fusion-dependent response was dependent on the stimulator of interferon genes STING but was independent of DNA, RNA and viral capsid. We suggest that membrane fusion is sensed as a danger signal with potential implications for defense against enveloped viruses and various conditions of giant-cell formation. | Animals, Cell Fusion, Chemokine CXCL10, HEK293 Cells, HeLa Cells, Herpesvirus 1, Human, Humans, Immunity, Innate, Interferon Type I, Leukocytes, Lymphocyte Activation, Macrophages, Membrane Fusion, Membrane Glycoproteins, Membrane Proteins, Mice, Mice, Knockout, Myeloid Differentiation Factor 88, Signal Transduction, Toll-Like Receptor 7, Toll-Like Receptor 9, Virus Internalization | null |
22,706,341 | 2012-11-09 | 2012-07-13 | 2040-3372 | Nanoscale | Ni@Fe₂O₃ heterodimers: controlled synthesis and magnetically recyclable catalytic application for dehalogenation reactions. | Nakhjavan Bahar, Tahir Muhammad Nawaz, Natalio Filipe, Panthöfer Martin, Gao Haitao, Dietzsch Michael, Andre Rute, Gasi Teuta, Ksenofontov Vadim, Branscheid Robert, Kolb Ute, Tremel Wolfgang | eng | null | Journal Article, Research Support, Non-U.S. Gov't | null | null | 22706341, 10.1039/c2nr12121b | Ni@Fe(2)O(3) heterodimer nanoparticles (NPs) were synthesized by thermal decomposition of organometallic reactants. After functionalization, these Ni@Fe(2)O(3) heterodimers became water soluble. The pristine heterodimeric NPs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Mössbauer spectroscopy and magnetic susceptibility measurements. A special advantage of the heterodimers lies in the fact that nanodomains of different composition can be used as catalysts for the removal of environmentally hazardous halogenated pollutants. | null | null |
22,706,340 | 2012-10-08 | 2021-10-21 | 1529-2916 | Nature immunology | The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells. | Kanaya Takashi, Hase Koji, Takahashi Daisuke, Fukuda Shinji, Hoshino Katsuaki, Sasaki Izumi, Hemmi Hiroaki, Knoop Kathryn A, Kumar Nachiket, Sato Mayuko, Katsuno Tatsuro, Yokosuka Osamu, Toyooka Kiminori, Nakai Kumiko, Sakamoto Ayako, Kitahara Yuuki, Jinnohara Toshi, McSorley Stephen J, Kaisho Tsuneyasu, Williams Ifor R, Ohno Hiroshi | eng | P01 AI056172 (NIAID NIH HHS, United States); R01 DK064730 (NIDDK NIH HHS, United States); (DK64730 (NIDDK NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | Proto-Oncogene Proteins c-ets, RANK Ligand, Spi-B protein, mouse, Tnfsf11 protein, mouse | IM | 22706340, ni.2352, 10.1038/ni.2352, PMC3704196, NIHMS380687, 16365394, 21383077, 11685223, 16093419, 4596277, 19828638, 17698607, 17442949, 9252325, 10229183, 21422150, 18785124, 10329609, 16713979, 16048549, 12960300, 11911822, 9384589, 19907495, 12393575, 16552796, 21057087, 8756716, 10583962, 2661061, 15071180, 8691135, 11031239, 15236187, 18523247, 1406622, 12456641, 15583020, 19549527, 17681175, 11984530, 10615124, 4810912, 16303744, 19935652, 4692973, 12015290, 9596705, 20417836 | Intestinal microfold cells (M cells) are an enigmatic lineage of intestinal epithelial cells that initiate mucosal immune responses through the uptake and transcytosis of luminal antigens. The mechanisms of M-cell differentiation are poorly understood, as the rarity of these cells has hampered analysis. Exogenous administration of the cytokine RANKL can synchronously activate M-cell differentiation in mice. Here we show the Ets transcription factor Spi-B was induced early during M-cell differentiation. Absence of Spi-B silenced the expression of various M-cell markers and prevented the differentiation of M cells in mice. The activation of T cells via an oral route was substantially impaired in the intestine of Spi-B-deficient (Spib(-/-)) mice. Our study demonstrates that commitment to the intestinal M-cell lineage requires Spi-B as a candidate master regulator. | Animals, Cell Differentiation, Cell Lineage, Epithelial Cells, Humans, Immunity, Mucosal, Intestinal Mucosa, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Knockout, Proto-Oncogene Proteins c-ets, RANK Ligand, T-Lymphocytes | null |
22,706,342 | 2013-01-11 | 2013-11-21 | 1460-2350 | Human reproduction (Oxford, England) | Effect of folate deficiency on promoter methylation and gene expression of Esr1, Cdh1 and Pgr, and its influence on endometrial receptivity and embryo implantation. | Gao Rufei, Ding Yubin, Liu Xueqing, Chen Xuemei, Wang Yingxiong, Long Chunlan, Li Shuang, Guo Liangrui, He Junlin | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Cdh1 Proteins, Cell Cycle Proteins, Estrogen Receptor alpha, Fzr1 protein, mouse, Receptors, Progesterone, Vitamin B Complex | IM | 22706342, des187, 10.1093/humrep/des187 | Folate, one of the B vitamins, provides the one-carbon units required for methylation. Folate deficiency has been associated with many pathologies. However, much less is known about the effect of it on human reproduction, especially on implantation. The establishment of uterine receptivity is crucial for successful embryo implantation. Gene expression can be influenced by both heredity and epigenetics such as DNA methylation. However, it is not known whether the methylation and expression of genes related to uterine receptivity can be affected by folate levels. To explore whether folate deficiency affected the epigenetic regulation of genes related to uterine receptivity, and their influence on implantation, we investigated the methylation and expression of cadherin 1 (Cdh1), progesterone receptor (Pgr) and estrogen receptor 1 (Esr1) genes during implantation and the implantation efficiency using a folate-deficient pregnant mouse model. | Animals, Cdh1 Proteins, Cell Cycle Proteins, DNA Methylation, Endometrium, Epigenesis, Genetic, Estrogen Receptor alpha, Female, Folic Acid Deficiency, Gene Expression Regulation, Immunoassay, Luminescence, Mice, Pregnancy, Pregnancy, Animal, Promoter Regions, Genetic, Receptors, Progesterone, Vitamin B Complex | null |
22,706,343 | 2012-10-02 | 2021-10-21 | 1735-3408 | Hepatitis monthly | Fibrosis progression in paired liver biopsies from HIV/HCV co-infected patients. | Schiavini Monica, Angeli Elena, Mainini Annalisa, Uberti-Foppa Caterina, Zerbi Pietro, Sagnelli Caterina, Cargnel Antonietta, Vago Gianluca, Duca Pier Giorgio, Giorgi Riccardo, Rizzardini Giuliano, Gubertini Guido | eng | null | Journal Article | null | null | 22706343, PMC3212761, 16327319, 10607241, 15973779, 1846395, 12801963, 7560864, 12567308, 11462196, 10191232, 11584380, 11170959, 14679458, 15619237, 14960533, 12512034, 10631857, 16945079, 9147999, 14643119, 8776313, 9305659, 16854955, 16908797, 17302246, 16182404, 11481613, 10098988, 10969344, 12823595, 15577649, 9380692, 18090048, 17316873, 10498659, 8098752, 11087200, 16355339, 12614468 | Chronic hepatitis C is more aggressive during HIV infection. Available data about risk factors of liver fibrosis in HIV/HCV co-infected patients derive from studies based on a single liver biopsy. | null | Antiretroviral therapy, HCV, HIV, Liver fibrosis |
22,706,335 | 2014-05-02 | 2022-04-10 | 1536-481X | Journal of glaucoma | Outcomes and complications of trabeculectomy enhanced with 5-fluorouracil in adults with glaucoma secondary to uveitis. | Chawla Anand, Mercieca Karl, Fenerty Cecilia, Jones Nicholas P | eng | null | Comparative Study, Journal Article | Antimetabolites, Mitomycin, Fluorouracil | IM | 22706335, 10.1097/IJG.0b013e318255dc07 | To analyze the long-term clinical outcomes of 5-fluorouracil (5FU)-enhanced trabeculectomy in patients with glaucoma secondary to uveitis (UG), to compare outcomes with those achieved elsewhere by primary mitomycin C-enhanced trabeculectomy and primary glaucoma drainage implant (GDI) surgery and to consider the optimal surgical approach in this group of patients. | Adult, Aged, Aged, 80 and over, Antimetabolites, Combined Modality Therapy, Female, Fluorouracil, Glaucoma, Glaucoma Drainage Implants, Humans, Intraocular Pressure, Male, Middle Aged, Mitomycin, Postoperative Complications, Retrospective Studies, Risk Factors, Trabeculectomy, Treatment Outcome, Uveitis, Young Adult | null |
22,706,346 | 2013-02-07 | 2012-10-01 | 1552-454X | Journal of biomolecular screening | Determination of appropriate stage of human-induced pluripotent stem cell-derived cardiomyocytes for drug screening and pharmacological evaluation in vitro. | Shinozawa Tadahiro, Imahashi Kenichi, Sawada Hiroshi, Furukawa Hatsue, Takami Kenji | eng | null | Journal Article | Calcium Channel Blockers, Ion Channels | IM | 22706346, 1087057112449864, 10.1177/1087057112449864 | Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) at different stages (approximate days 30, 60, and 90) were used to determine the appropriate stage for functional and morphological assessment of drug effects in vitro. The hiPS-CMs had spontaneous beating activity, and β-adrenergic function was comparable in all stages of differentiation. Microelectrode array analyses using ion channel blockers indicated that the electrophysiological properties of these ion channels were comparable at all differentiation stages. Ultrastructural analysis using electron microscopy showed that myofibrillar structures at days 60 and 90 were similarly distributed and more mature than that at day 30. Analysis of motion vectors in contracting cells showed that the velocity of contraction was the highest at day 90 and was the most mature among the three stages. Gene expression analysis demonstrated that expression of some genes related to myofilament and sarcoplasmic reticulum increased with maturation of morphological and contractile properties. In conclusion, day 30 cardiomyocytes are useful for basic screening such as the assessment of electrophysiological properties, and days 60 and 90 are the appropriate differentiation stage for morphological assays. For the assay of contractile function associated with subcellular components such as sarcoplasmic reticulum, day 90 cardiomyocytes are the most suitable. | Action Potentials, Calcium Channel Blockers, Cell Differentiation, Drug Evaluation, Preclinical, Gene Expression Profiling, Humans, Induced Pluripotent Stem Cells, Ion Channels, Microelectrodes, Microscopy, Electron, Transmission, Myocardial Contraction, Myocytes, Cardiac, Myofibrils, Sarcoplasmic Reticulum, Time Factors | null |
22,706,344 | 2013-01-25 | 2019-07-27 | 1349-3329 | The Tohoku journal of experimental medicine | Interleukin-6 maintains glucose homeostasis to support strenuous masseter muscle activity in mice. | Tsuchiya Masahiro, Kiyama Tomomi, Tsuchiya Shinobu, Takano Hirohisa, Nemoto Eiji, Sasaki Keiichi, Watanabe Makoto, Sugawara Shunji, Endo Yasuo | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Interleukin-6, RNA, Messenger, Socs3 protein, mouse, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins, interleukin-6, mouse, Glycogen, Glucose | IM | 22706344, DN/JST.JSTAGE/tjem/227.109, 10.1620/tjem.227.109 | The cytokine interleukin-6 (IL-6) is released from working skeletal muscles and reportedly plays key roles in their glucose homeostasis. However, it is unclear whether IL-6 plays such roles in the masseter muscle (MM), which is important in normal and pathological chewing behaviors, such as bruxism and/or prolonged clenching. When restrained (R+) in a narrow cylinder blocked at the front end with a thin plastic strip, a mouse gnaws away (G+) the strip to escape. The absolute weight of plastic gnawed away serves as an index of MM activity. Using this model, we examined the roles of IL-6 in MM with the following results. R+G+ increased the expression levels of IL-6 and glucose transporter 4 (Glut4) mRNAs in MM and the serum level of IL-6 protein. IL-6-deficient mice exhibited about 60% less gnawing activity than wild-type mice at 3-4 h after the start of R+G+, slower recovery of glycogen levels (indicating poorer glucose supply) in MM after R+G+, and no significant change in Glut4 mRNA in MM upon R+G+. During an R+G+ test conducted after "training" (repeated R+G+ sessions), wild-type mice exhibited greater gnawing activity than untrained controls, but no increase in IL-6 mRNA in MM. IL-6 mRNA increased in MM when hard food was eaten by mice raised on soft food for 3 weeks from weaning, but not in those raised on (accustomed to) hard food. Thus, IL-6 may maintain glucose homeostasis in MM in support of unusually strenuous activity, but not of accustomed activity levels. | Animals, Food, Gene Expression Regulation, Glucose, Glycogen, Hardness, Homeostasis, Interleukin-6, Masseter Muscle, Mastication, Mice, Mice, Inbred BALB C, Mice, Knockout, Models, Biological, RNA, Messenger, Restraint, Physical, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins | null |
22,706,347 | 2013-01-03 | 2012-08-15 | 1552-454X | Journal of biomolecular screening | A unique 3D in vitro cellular invasion assay. | Quail Daniela F, Maciel Tamara J, Rogers Kem, Postovit Lynne M | eng | MOP 89714 (Canadian Institutes of Health Research, Canada); PLS 95381 (Canadian Institutes of Health Research, Canada) | Journal Article, Research Support, Non-U.S. Gov't | NODAL protein, human, Nodal Protein | IM | 22706347, 1087057112449863, 10.1177/1087057112449863 | Three-dimensional (3D) cell culture techniques using a bioreactor have been used to co-culture various breast cancer cell lines. Comparisons between 3D co-cultures containing different proportions of breast cancer cell lines have been made with respect to cluster size, cell surface marker distribution, and Ki67 expression. Furthermore, an observed difference in invasion through collagen between co-cultures has been briefly reported. However, these assays have not yet been developed into a quantifiable methodology to assess the effects of drugs and/or microenvironments on cellular invasion. From a cancer perspective, two important aspects of cellular invasion that are often left out of in vitro assays are considerations about the 3D structural heterogeneity of the primary tumor and the ability of cells to migrate in all directions. Accordingly, we have taken advantage of the methodology previously described for 3D cell culture techniques and have developed a 3D invasion assay using cell clusters that can be used to assess the effects of different drugs and treatment conditions on cancer cell invasion. We also describe a novel whole-mount technique that permits fluorescence-based immunolocalization of proteins through the entire tumorsphere, without the need for sectioning. Our assay provides a simple, inexpensive, and physiologically relevant context to study cellular invasion in vitro, in a way that recapitulates an in vivo milieu. | Bioreactors, Breast Neoplasms, Cell Migration Assays, Extracellular Matrix, Female, Fluorescent Antibody Technique, Humans, MCF-7 Cells, Microscopy, Confocal, Neoplasm Invasiveness, Nodal Protein | null |
22,706,348 | 2013-01-03 | 2021-12-03 | 1552-454X | Journal of biomolecular screening | A yeast-based in vivo bioassay to screen for class I phosphatidylinositol 3-kinase specific inhibitors. | Fernández-Acero Teresa, Rodríguez-Escudero Isabel, Vicente Francisca, Monteiro Maria Cândida, Tormo José R, Cantizani Juan, Molina María, Cid Víctor J | eng | null | Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't | ATP-Binding Cassette Transporters, Furans, PI103, Protein Kinase Inhibitors, Pyridines, Pyrimidines, SNQ2 protein, S cerevisiae, Saccharomyces cerevisiae Proteins, Sodium Dodecyl Sulfate, 3-Phosphoinositide-Dependent Protein Kinases, Protein Serine-Threonine Kinases | IM | 22706348, 1087057112450051, 10.1177/1087057112450051 | The phosphatidylinositol 3-kinase (PI3K) pathway couples receptor-mediated signaling to essential cellular functions by generating the lipid second messenger phosphatidylinositol-3,4,5-trisphosphate. This pathway is implicated in multiple aspects of oncogenesis. A low-cost bioassay that readily measures PI3K inhibition in vivo would serve as a valuable tool for research in this field. Using heterologous expression, we have previously reconstituted the PI3K pathway in the model organism Saccharomyces cerevisiae. On the basis of the fact that the overproduction of PI3K is toxic in yeast, we tested the ability of commercial PI3K inhibitors to rescue cell growth. All compounds tested counteracted the PI3K-induced toxicity. Among them, 15e and PI-103 were the most active. Strategies to raise the intracellular drug concentration, specifically the use of 0.003% sodium dodecyl sulfate and the elimination of the Snq2 detoxification pump, optimized the bioassay by enhancing its sensitivity. The humanized yeast-based assay was then tested on a pilot scale for high-throughput screening (HTS) purposes using a collection of natural products of microbial origin. From 9600 extracts tested, 0.6% led to a recovery of yeast growth reproducibly, selectively, and in a dose-dependent manner. Cumulatively, we show that the developed PI3K inhibition bioassay is robust and applicable to large-scale HTS. | 3-Phosphoinositide-Dependent Protein Kinases, ATP-Binding Cassette Transporters, Furans, High-Throughput Screening Assays, Humans, Protein Kinase Inhibitors, Protein Serine-Threonine Kinases, Pyridines, Pyrimidines, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sodium Dodecyl Sulfate | null |
22,706,349 | 2013-01-03 | 2024-02-02 | 1552-454X | Journal of biomolecular screening | MScreen: an integrated compound management and high-throughput screening data storage and analysis system. | Jacob Renju T, Larsen Martha J, Larsen Scott D, Kirchhoff Paul D, Sherman David H, Neubig Richard R | eng | P30 CA046592 (NCI NIH HHS, United States); 5 P30 CA46592 (NCI NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural | RNA, Small Interfering, Small Molecule Libraries | IM | 22706349, 1087057112450186, 10.1177/1087057112450186, PMC3600606, NIHMS448427, 10838414, 20482787, 19531661, 12565011, 20609414, 18216396, 17405872, 16533710, 17316541, 19332539, 21844328, 19239364, 20809896 | High-throughput screening (HTS) has historically been used by the pharmaceutical industry to rapidly test hundreds of thousands of compounds to identify potential drug candidates. More recently, academic groups have used HTS to identify new chemical probes or small interfering RNA (siRNA) that can serve as experimental tools to examine the biology or physiology of novel proteins, processes, or interactions. HTS presents a significant challenge with the vast and complex nature of data generated. This report describes MScreen, a Web-based, open-source cheminformatics application for chemical library and siRNA plate management, primary HTS and dose-response data handling, structure search, and administrative functions. Each project in MScreen can be secured with passwords or shared in an open-information environment that enables collaborators to easily compare data from many screens, providing a useful means to identify compounds with desired selectivity. Unique features include compound, substance, mixture, and siRNA plate creation and formatting; automated dose-response fitting and quality control (QC); and user, target, and assay method administration. MScreen provides an effective means to facilitate HTS information handling and analysis in the academic setting so that users can efficiently view their screening data and evaluate results for follow-up. | Databases, Chemical, High-Throughput Screening Assays, Information Storage and Retrieval, Internet, RNA, Small Interfering, Small Molecule Libraries | null |
22,706,350 | 2013-01-03 | 2018-12-01 | 1552-454X | Journal of biomolecular screening | Development of a high-content screening assay panel to accelerate mechanism of action studies for oncology research. | Towne Danli L, Nicholl Emily E, Comess Kenneth M, Galasinski Scott C, Hajduk Philip J, Abraham Vivek C | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Antineoplastic Agents, Cytochromes c | IM | 22706350, 1087057112450050, 10.1177/1087057112450050 | Efficient elucidation of the biological mechanism of action of novel compounds remains a major bottleneck in the drug discovery process. To address this need in the area of oncology, we report the development of a multiparametric high-content screening assay panel at the level of single cells to dramatically accelerate understanding the mechanism of action of cell growth-inhibiting compounds on a large scale. Our approach is based on measuring 10 established end points associated with mitochondrial apoptosis, cell cycle disruption, DNA damage, and cellular morphological changes in the same experiment, across three multiparametric assays. The data from all of the measurements taken together are expected to help increase our current understanding of target protein functions, constrain the list of possible targets for compounds identified using phenotypic screens, and identify off-target effects. We have also developed novel data visualization and phenotypic classification approaches for detailed interpretation of individual compound effects and navigation of large collections of multiparametric cellular responses. We expect this general approach to be valuable for drug discovery across multiple therapeutic areas. | Antineoplastic Agents, Apoptosis, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Cytochromes c, DNA Damage, Dose-Response Relationship, Drug, Drug Discovery, Drug Screening Assays, Antitumor, High-Throughput Screening Assays, Humans, Image Processing, Computer-Assisted, Microscopy, Fluorescence, Mitochondria | null |
22,706,353 | 2015-02-26 | 2012-06-18 | 1120-9763 | Epidemiologia e prevenzione | [Sugar like alcohol?]. | Tromba Cinzia | ita | null | News | Carbohydrates, Fructose, Sucrose | IM | 22706353, 1321 | null | Alcohol Drinking, Beverages, Carbohydrates, Cardiovascular Diseases, Diet, Fructose, Humans, Italy, Legislation, Food, Malnutrition, Obesity, Pancreatitis, Smoking, Substance-Related Disorders, Sucrose | null |
22,706,352 | 2015-02-26 | 2012-06-18 | 1120-9763 | Epidemiologia e prevenzione | [The evolution of the National Centre for Screening Monitoring]. | Zappa Marco, Federici Antonio | ita | null | Editorial | null | IM | 22706352, 1319 | null | European Union, Humans, Interinstitutional Relations, Italy, Mass Screening, National Health Programs | null |
22,706,351 | 2015-02-26 | 2018-12-01 | 1120-9763 | Epidemiologia e prevenzione | [Moniter project: uncertainty, transparency and need of in-depth discussion of the results]. | Ranzi Andrea, Carra Luca, Candela Silvia | ita | null | Letter, Comment | null | IM | 22706351, 1316 | null | Environmental Pollution | null |
22,706,354 | 2015-02-26 | 2017-11-16 | 1120-9763 | Epidemiologia e prevenzione | [False positives and conflicts of interest]. | Seniori Costantini Adele | ita | null | News | null | IM | 22706354, 1322 | null | Bias, Conflict of Interest, Expert Testimony, False Positive Reactions, Humans, International Agencies, Neoplasms, Research Personnel, Risk | null |
22,706,357 | 2015-02-26 | 2022-12-07 | 1120-9763 | Epidemiologia e prevenzione | [Suicide mortality among cancer patients]. | Crocetti Emanuele, Buzzoni Carlotta, Caldarella Adele, Intrieri Teresa, Manneschi Gianfranco, Sacchettini Claudio, Paci Eugenio, Miccinesi Guido | ita | null | English Abstract, Journal Article | null | IM | 22706357, 1293 | to evaluate the excess risk in the deaths due to suicide in a huge case-series of cancer patients and in particular in a group with recent diagnosis. | Adolescent, Adult, Age Distribution, Aged, Child, Cohort Studies, Female, Humans, Italy, Male, Middle Aged, Neoplasms, Palliative Care, Prognosis, Risk, Suicide, Terminal Care, Young Adult, Suicide Prevention | null |
22,706,358 | 2015-02-26 | 2022-12-07 | 1120-9763 | Epidemiologia e prevenzione | [Results and cost evaluation of triage with high risk HPV test in cervical cancer screening. A pilot study in Piedmont (North-West Italy)]. | Magnani Corrado, Gillio Tos Anna, De Marco Laura, Calvia Maria, Cipelletti Angela, Bestagini Piero, Pagano Eva, Segnan Nereo, Ronco Guglielmo | ita | null | Journal Article | DNA Probes, HPV | IM | 22706358, 1299 | causal relation between high risk Papilloma virus and cervical carcinoma is definitely ascertained. HPV test is suggested both as primary screening test and as triage test for selecting women who should undergo colposcopy examination. Evidence is clear for triage after ASC-US cytology. A recent study suggested the implementation after LSIL cytology in women 35 or older but the issue is controversial.We present a pilot study on the implementation of HPV test triage in the framework of cervical cancer screening. The study was conducted in respect to: participation, predictive value, and cost analysis, separately for ASC-US and LSIL cytology. | Adult, Alphapapillomavirus, Colposcopy, Cost-Benefit Analysis, Costs and Cost Analysis, DNA Probes, HPV, Early Detection of Cancer, Female, Gammapapillomavirus, Humans, Italy, Middle Aged, Papanicolaou Test, Papillomavirus Infections, Pilot Projects, Predictive Value of Tests, Prevalence, Risk, Triage, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms, Young Adult | null |
22,706,355 | 2015-02-26 | 2018-12-01 | 1120-9763 | Epidemiologia e prevenzione | [Considerations on suicide deaths of cancer patients]. | Candela Silvia | ita | null | News, Comment | null | IM | 22706355, 1323 | null | Female, Humans, Male, Neoplasms, Suicide | null |
22,706,356 | 2015-02-26 | 2012-06-18 | 1120-9763 | Epidemiologia e prevenzione | [European guidelines on opioid use, a tool to improve clinical practice]. | Caraceni Augusto | ita | null | News | Narcotics | IM | 22706356, 1325 | null | Europe, Humans, Narcotics, Neoplasms, Pain, Palliative Care, Practice Guidelines as Topic, Professional Practice | null |
22,706,363 | 2015-02-26 | 2017-11-16 | 1120-9763 | Epidemiologia e prevenzione | [Errors in personal identification codes and their consequencies on prevalence estimations using record linkage]. | Cislaghi Cesare, Zocchetti Carlo, Russo Antonio | ita | null | Journal Article | null | IM | 22706363, 1327 | null | Bias, Cross-Sectional Studies, Drug Prescriptions, Humans, Italy, Medical Record Linkage, Patient Identification Systems | null |
22,706,371 | 2012-10-09 | 2021-10-21 | 1420-3049 | Molecules (Basel, Switzerland) | A monoclonal antibody-based ELISA for multiresidue determination of avermectins in milk. | Wang Chunmei, Wang Zhanhui, Jiang Wenxiao, Mi Tiejun, Shen Jianzhong | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Antibodies, Monoclonal, Antigens, Ivermectin, avermectin, Methanol | IM | 22706371, molecules17067401, 10.3390/molecules17067401, PMC6268685, 8600758, 16302747, 16950666, 16152926, 11959474, 17969695, 19538934, 19519244, 12180682, 19259453, 10794653, 17481406, 19839635, 16910699, 20345138, 7752622, 11114113, 21742111, 11368571 | Due to the widespread use and potential toxicity of avermectins (AVMs), multi-residue monitoring of AVMs in edible tissues, especially in milk, has become increasingly important. With the aim of developing a broad-selective immunoassay for AVMs, a broad-specific monoclonal antibody (Mab) was raised. Based on this Mab, a homologous indirect enzyme-linked immunosorbent assay (ELISA) for the rapid detection of AVMs in milk was developed. Under the optimized conditions, the IC₅₀ values in assay buffer were estimated to be 3.05 ng/mL for abamectin, 13.10 ng/mL for ivermectin, 38.96 ng/mL for eprinomectin, 61.00 ng/mL for doramectin, 14.38 ng/mL for emamectin benzoate. Detection capability (CCβ) of the ELISA was less than 5 ng/mL and 2 ng/mL in milk samples prepared by simple dilution and solvent extraction, respectively. The optimized ELISA was used to quantify AVMs in milk samples spiked at different amounts. The mean recovery and coefficient of variation (CV) were 95.90% and 15.42%, respectively. The Mab-based ELISA achieved a great improvement in AVMs detection. Results proved this broad-selective ELISA would be useful for the multi-residue determination of AVMs in milk without purification process. | Animals, Antibodies, Monoclonal, Antigens, Cattle, Enzyme-Linked Immunosorbent Assay, Female, Hydrogen-Ion Concentration, Ivermectin, Methanol, Mice, Mice, Inbred BALB C, Milk, Temperature | null |
22,706,366 | 2015-02-26 | 2016-11-25 | 1120-9763 | Epidemiologia e prevenzione | [Macro factors in risk and macro differences in epigenetics]. | Stazi Maria Antonietta, Nisticò Lorenza, Serino Laura | ita | null | Journal Article | MicroRNAs | IM | 22706366, 1339 | null | Adult, Cohort Studies, CpG Islands, DNA Methylation, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, MicroRNAs, Middle Aged, Risk Factors, Scotland, Socioeconomic Factors, United Kingdom | null |
22,706,359 | 2015-02-26 | 2022-12-07 | 1120-9763 | Epidemiologia e prevenzione | [Immigration from countries with a strong migratory pressure and participation in cervical cancer screening program in the Local Health Unit 2, Umbria Region. Impact on the probability of high-grade lesions and cervical cancer]. | Vallesi Giuseppe, Bietta Carla, Marri Maria, Petrella Marco | ita | null | Journal Article | null | IM | 22706359, 1301 | to measure the risk of having serious lesions and cervical cancer for immigrant women, by evaluating the impact of their lack of participation in the previous rounds. | Adenocarcinoma, Adult, Africa, Northern, Asia, Carcinoma, Squamous Cell, Colposcopy, Community Participation, Early Detection of Cancer, Emigrants and Immigrants, Emigration and Immigration, Female, Humans, Italy, Latin America, Middle Aged, Papanicolaou Test, Poverty, Retrospective Studies, Social Conditions, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms | null |
22,706,361 | 2015-02-26 | 2022-12-07 | 1120-9763 | Epidemiologia e prevenzione | [Human Papilloma Virus (HPV), cervical cancer incidence and screening uptake: differences among Northern, Central and Southern Italy]. | Giorgi Rossi Paolo, Chini Francesco, Borgia Piero, Guasticchi Gabriella, Carozzi Francesca Maria, Confortini Massimo, Angeloni Claudio, Buzzoni Carlotta, Buonaguro Franco Maria | ita | null | Comparative Study, English Abstract, Journal Article, Review | null | IM | 22706361, 1313 | this article presents a review of evidences about Human Papillomavirus (HPV) and cervical cancer in Italy, highlighting geographical differences. | Adenocarcinoma, Adult, Aged, Carcinoma, Squamous Cell, Colposcopy, Early Detection of Cancer, Female, Human papillomavirus 16, Human papillomavirus 18, Humans, Incidence, Italy, Middle Aged, Morbidity, Papanicolaou Test, Papillomavirus Infections, Prevalence, Retrospective Studies, Social Change, Survival Rate, Uterine Cervical Neoplasms, Young Adult, Uterine Cervical Dysplasia | null |
22,706,373 | 2012-10-09 | 2021-10-21 | 1420-3049 | Molecules (Basel, Switzerland) | NIR spectroscopic properties of aqueous acids solutions. | Omar Ahmad Fairuz, Atan Hanafi, Matjafri Mohd Zubir | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Acids, Malates, Oxalates, Solutions, Tartrates, Citric Acid, malic acid, tartaric acid | IM | 22706373, molecules17067440, 10.3390/molecules17067440, PMC6268505, 11087466, 11675027, 19067467 | Acid content is one of the important quality attributes in determining the maturity index of agricultural product, particularly fruits. Despite the fact that much research on the measurement of acidity in fruits through non-destructive spectroscopy analysis at NIR wavelengths between 700 to 1,000 nm has been conducted, the same response towards individual acids is not well known. This paper presents NIR spectroscopy analysis on aqueous citric, tartaric, malic and oxalic solutions through quantitative analysis by selecting a set of wavelengths that can best be used to measure the pH of the solutions. The aquaphotomics study of the acid solutions has generated R² above 0.9 for the measurement of all acids. The most important wavelengths for pH are located at 918-925 nm and 990-996 nm, while at 975 nm for water. | Acids, Citric Acid, Fruit, Hydrogen-Ion Concentration, Malates, Oxalates, Solutions, Spectroscopy, Near-Infrared, Tartrates | null |
22,706,370 | 2012-10-09 | 2021-10-21 | 1420-3049 | Molecules (Basel, Switzerland) | Application of 2,3-naphthalenediamine in labeling natural carbohydrates for capillary electrophoresis. | Kuo Chien-Yuan, Wang Shwu-Huey, Lin Chunchi, Liao Sylvain Kuo-Shiang, Hung Wei-Ting, Fang Jim-Min, Yang Wen-Bin | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Carbohydrates, Polysaccharides, 2,3-diaminonaphthalene, Heparin, 2-Naphthylamine | IM | 22706370, molecules17067387, 10.3390/molecules17067387, PMC6269047, 11836115, 8900948, 18467102, 21898463, 4086626, 20674212, 11755740, 21394840, 17474083, 16798741, 11278930, 21204109, 18422361, 21145794, 17080489, 18706565, 21720308, 2729565, 16800030, 21910131, 20303496, 9271065, 8900941, 21242944, 19960495, 18841350, 8601201, 11293587, 10596821, 20335985, 17996095, 21469955 | Neutral and acidic monosaccharide components in Ganoderma lucidum polysaccharide are readily labeled with 2,3-naphthalenediamine, and the resulting saccharide-naphthimidazole (NAIM) derivatives are quantified by capillary electrophoresis (CE) in borate buffer. Using sulfated-α-cyclodextrin as the chiral selector, enantiomers of monosaccharide-NAIMs are resolved on CE in phosphate buffer, allowing a simultaneous determination of the absolute configuration and sugar composition in the mucilage polysaccharide of a medicinal herb Dendrobium huoshanense. Together with the specific enzymatic reactions of various glycoside hydrolases on the NAIM derivatives of glycans, the structures of natural glycans can be deduced from the digestion products identified by CE analysis. Though heparin dissachrides could be successfully derived with the NAIM-labeling method, the heparin derivatives with the same degree of sulfation could not be separated by CE. | 2-Naphthylamine, Carbohydrates, Dendrobium, Electrophoresis, Capillary, Heparin, Polysaccharides, Reishi, Staining and Labeling | null |
22,706,374 | 2012-10-09 | 2023-10-04 | 1420-3049 | Molecules (Basel, Switzerland) | An oxidized squalene derivative from Protium subserratum Engl. (Engl.) growing in Peru. | Lokvam John, Fine Paul V A | eng | null | Journal Article, Research Support, U.S. Gov't, Non-P.H.S. | 25,30-dicarboxy-26,27,28,29-tetraacetoxy-10,11,14,15-tetrahydrosqualene, Plant Extracts, Squalene | IM | 22706374, molecules17067451, 10.3390/molecules17067451, PMC6268440, 15286371, 21642176, 11868668, 24015520, 16676208 | Protium subserratum (Burseraceae) is a neotropical tree species that is comprised of several habitat-specific ecotypes having distinct defense chemical profiles. A previously unknown triterpene, 25,30-dicarboxy-26,27,28,29-tetraacetoxy-10,11,14,15-tetrahydrosqualene, was isolated from P. subserratum young leaf tissue of one ecotype growing in Peru. The structure of 1 was determined by spectroscopic study, including 1 and 2D nuclear magnetic resonance experiments. | Burseraceae, Nuclear Magnetic Resonance, Biomolecular, Oxidation-Reduction, Peru, Plant Extracts, Plant Leaves, Squalene | null |
22,706,372 | 2012-10-09 | 2021-10-21 | 1420-3049 | Molecules (Basel, Switzerland) | Application of 4D-QSAR studies to a series of raloxifene analogs and design of potential selective estrogen receptor modulators. | Sodero Ana Carolina Rennó, Romeiro Nelilma Correia, da Cunha Elaine Fontes Ferreira, de Oliveira Magalhaães Uiaran, de Alencastro Ricardo Bicca, Rodrigues Carlos Rangel, Cabral Lúcio Mendes, Castro Helena Carla, Albuquerque Magaly Girão | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Estrogen Receptor alpha, Selective Estrogen Receptor Modulators, Raloxifene Hydrochloride | IM | 22706372, molecules17067415, 10.3390/molecules17067415, PMC6268799, 22484805, 9003514, 16231199, 20657478, 10592235, 9338790, 15658851, 11046073, 10481161, 11815274, 20957105, 11795383, 9770304, 11749430, 12546568, 18661245, 9391160, 10732322, 12549769, 15713417, 16083919, 22176952 | Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied on a series of 54 2-arylbenzothiophene derivatives, synthesized by Grese and coworkers, based on raloxifene (an estrogen receptor-alpha antagonist), and evaluated as ERa ligands and as inhibitors of estrogen-stimulated proliferation of MCF-7 breast cancer cells. The conformations of each analogue, sampled from a molecular dynamics simulation, were placed in a grid cell lattice according to three trial alignments, considering two grid cell sizes (1.0 and 2.0 Å). The QSAR equations, generated by a combined scheme of genetic algorithms (GA) and partial least squares (PLS) regression, were evaluated by "leave-one-out" cross-validation, using a training set of 41 compounds. External validation was performed using a test set of 13 compounds. The obtained 4D-QSAR models are in agreement with the proposed mechanism of action for raloxifene. This study allowed a quantitative prediction of compounds' potency and supported the design of new raloxifene analogs. | Estrogen Receptor alpha, Inhibitory Concentration 50, Molecular Conformation, Molecular Dynamics Simulation, Protein Binding, Quantitative Structure-Activity Relationship, Raloxifene Hydrochloride, Selective Estrogen Receptor Modulators | null |
22,706,368 | 2015-02-26 | 2012-06-18 | 1120-9763 | Epidemiologia e prevenzione | [Distortions and distractions in the scientific activity]. | De Marchi Bruna | ita | null | Journal Article | null | IM | 22706368, 1341 | null | Ethics, Research, Humans, Quality Control, Reproducibility of Results, Research Personnel, Scientific Misconduct | null |
22,706,365 | 2015-02-26 | 2015-11-19 | 1120-9763 | Epidemiologia e prevenzione | [Depressive symptoms, a challenge for the community of L'Aquila after the earthquake of 2009]. | Gigantesco Antonella, Mirante Nadia, Minardi Valentina, Tarolla Emanuele, Cofini Vincenza, Carbonelli Anna, Diodati Gianfranco, Granchelli Carla, Mancini Cristiana, D'Argenio Paolo, Trinito Massimo Oddone, Salmaso Stefania | ita | null | Journal Article | null | IM | 22706365, 1338 | null | Adolescent, Adult, Aged, Anhedonia, Depressive Disorder, Earthquakes, Humans, Italy, Middle Aged, Prevalence, Surveys and Questionnaires, Young Adult | null |
22,706,360 | 2015-02-26 | 2017-11-16 | 1120-9763 | Epidemiologia e prevenzione | [Impact of cigarette packages warning labels in relation to tobacco-smoking dependence and motivation to quit]. | Mannocci Alice, Antici Daniele, Boccia Antonio, La Torre Giuseppe | ita | null | Journal Article, Multicenter Study | null | IM | 22706360, 1306 | the principal aim was to assess the impact of health warnings on cigarette packages in Italy, the reduction of daily number of cigarette smoked, in relationship to the tobacco-smoking dependence and motivation to quit. The second aim was to compare the impact of text warnings versus graphi depictions. | Adult, Attitude to Health, Consumer Health Information, Cross-Sectional Studies, Emotions, Female, Habits, Health Behavior, Health Knowledge, Attitudes, Practice, Humans, Male, Medical Illustration, Middle Aged, Motivation, Outpatient Clinics, Hospital, Product Labeling, Rome, Sampling Studies, Smoking, Smoking Prevention, Surveys and Questionnaires, Tobacco Use Disorder, Young Adult | null |
22,706,376 | 2012-10-09 | 2023-10-04 | 1420-3049 | Molecules (Basel, Switzerland) | Guanidine affects differentially the twitch response of diaphragm, extensor digitorum longus and soleus nerve-muscle preparations of mice. | Ferrari Rosana, Rodrigues-Simioni Léa, da Cruz Höfling Maria Alice | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Guanidine, Calcium | IM | 22706376, molecules17067503, 10.3390/molecules17067503, PMC6268877, 14592857, 1417360, 11275359, 21926190, 16759829, 21586364, 1660254, 5927905, 5217455, 13358734, 8102841, 4304169, 6247422, 2899307, 2520354, 6033586, 1733232, 1683760, 2457185, 192882, 9559322, 16192771, 10400298, 3367195, 451525, 8355723, 17286272, 194021, 17493926, 1262852, 4418697, 12770515, 8051290, 1761971, 10813361, 8817811, 20664073, 16418275, 7499483, 10998639, 2417269, 8036908, 6213636, 9662440, 209168, 22013216, 7320866, 9147031, 10825439, 3264838, 19352164, 16242636, 9147030, 6605493, 10533574, 21698699 | Guanidine has been used with some success to treat myasthenia gravis and myasthenic syndrome because it increases acetylcholine release at nerve terminals through K⁺, Na⁺ and Ca²⁺ channels-involving mechanisms. Currently, guanidine derivatives have been proposed for treatment of several diseases. Studies aimed at providing new insights to the drug are relevant. Experimentally, guanidine (10 mM) induces on mouse phrenic nerve-diaphragm (PND) preparations neurotransmission facilitation followed by blockade and a greatest secondary facilitation after its removal from bath. Herein, we hypothesized that this peculiar triphasic response may differ in muscles with distinct twitch/metabolic characteristics. Morphological alterations and contractile response of PND, extensor digitorum longus (EDL) and soleus (SOL) preparations incubated with guanidine (10 mM) for 15, 30, 60 min were analyzed. Guanidine concentrations of 5 mM (for PND and EDL) and 1 mM (for EDL) were also tested. Guanidine triphasic effect was only observed on PND regardless the concentration. The morphological alterations in muscle tissue varied along time but did not impede the PND post-wash facilitation. Higher doses (20-25 mM) did not increase EDL or SOL neurotransmission. The data suggest a complex mechanism likely dependent on the metabolic/contractile muscle phenotype; muscle fiber types and density/type of ion channels, sarcoplasmic reticulum and mitochondria organization may have profound impact on the levels and isoform expression pattern of Ca²⁺ regulatory membrane proteins so reflecting regulation of calcium handling and contractile response in different types of muscle. | Animals, Calcium, Diaphragm, Guanidine, Male, Mice, Muscle Contraction, Muscle, Skeletal, Myography, Neuromuscular Junction, Synaptic Transmission | null |
22,706,375 | 2012-10-09 | 2024-04-04 | 1420-3049 | Molecules (Basel, Switzerland) | Ionic liquids--promising but challenging solvents for homogeneous derivatization of cellulose. | Gericke Martin, Fardim Pedro, Heinze Thomas | eng | null | Journal Article, Research Support, Non-U.S. Gov't, Review | Ionic Liquids, Solvents, Cellulose | IM | 22706375, molecules17067458, 10.3390/molecules17067458, PMC6269012, 16622493, 17691840, 21116514, 17956132, 15730322, 21701727, 17086590, 21337342, 19031387, 19199606, 11982358, 20923202, 15861454, 15948229, 19116894, 21452895, 20462222, 11777383, 22406063, 12769563, 21740062, 18507453, 20959901, 20972501, 20511289, 21827163, 15053626, 24750596, 21455515, 23540980, 19722554, 15638537, 20481539, 20145862, 21742316, 19384978, 21797215, 19623581, 18693699, 16538244, 22098258, 18822323, 19854462, 19783957, 20218725, 22171976, 20111784, 21301714, 21950594, 17429805, 24750754, 22179764, 17154453, 15584076, 21608091, 21170465, 15320715, 18004839, 21755585, 19757807, 18311635, 19754182, 19338350, 21107793, 22266483, 15002983, 16820978, 18774859, 21858359, 20728347, 15053678 | In the past decade, ionic liquids (ILs) have received enormous interest as solvents for cellulose. They have been studied intensively for fractionation and biorefining of lignocellulosic biomass, for dissolution of the polysaccharide, for preparation of cellulosic fibers, and in particular as reaction media for the homogeneous preparation of highly engineered polysaccharide derivatives. ILs show great potential for application on a commercial scale regarding recyclability, high dissolution power, and their broad structural diversity. However, a critical analysis reveals that these promising features are combined with serious drawbacks that need to be addressed in order to utilize ILs for the efficient synthesis of cellulose derivatives. This review presents a comprehensive overview about chemical modification of cellulose in ILs. Difficulties encountered thereby are discussed critically and current as well as future developments in this field of polysaccharide research are outlined. | Cellulose, Ionic Liquids, Solvents | null |
22,706,362 | 2015-02-26 | 2016-11-25 | 1120-9763 | Epidemiologia e prevenzione | [Meaningful words? Cancer screening communication in Italy]. | Cogo Carla, Petrella Marco | ita | null | Journal Article, Review | null | IM | 22706362, 1350 | Over the last ten years, Italian work groups of communication within The National Centre for Screening Monitoring have been working on various aspects of communication in screening: quality surveys, information materials, guidelines, websites, and training. This has been done taking into account that good quality information must be clear, accessible, up to date, evidence based, clear about its limitations and capable of indicating further sources of information. Whenever possible, information has been developed in collaboration with the target groups: citizens but also health professionals. However, if good quality information must be clear about benefits and harms, the communication of quantitative information is particularly complex in cancer screening. Moreover, receiving more information on risks and benefits does not seem to modify participation. In addition, more balanced information does not entail that a person will include it in the decision process.Throughout several focus groups, citizens have made it clear that the information received from the programmes was only a part of the decisional process in which other elements were just as, if not more, important: trust in doctors, family and friends, perception of health authority efficiency, personal experiences, inconsistencies in information or public disagreements with other credible sources. Such elements can be seen as an opportunity to strengthen partnerships with professional and advocacy groups and to cooperate more efficiently with media and specialists from different fields. | Attitude to Health, Communication, Communication Barriers, Community Participation, Decision Making, Early Detection of Cancer, Female, Focus Groups, Health Promotion, Humans, Information Dissemination, Information Seeking Behavior, Internet, Interpersonal Relations, Italy, Male, Mass Media, Motivation, Narration, Nonverbal Communication, Persuasive Communication, Vaccination | null |
22,706,378 | 2013-01-07 | 2021-10-21 | 1468-6244 | Journal of medical genetics | Rare TP53 genetic variant associated with glioma risk and outcome. | Egan Kathleen M, Nabors L Burton, Olson Jeffrey J, Monteiro Alvaro N, Browning James E, Madden Melissa H, Thompson Reid C | eng | R01 CA116174 (NCI NIH HHS, United States); R01CA116174 (NCI NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't | TP53 protein, human, Tumor Suppressor Protein p53 | IM | 22706378, jmedgenet-2012-100941, 10.1136/jmedgenet-2012-100941, PMC3576847, NIHMS442597, 21203894, 20831747, 18772890, 20126254, 20554195, 21946351 | Validation of a recent finding linking a rare variant in TP53 to the risk of glioma, the most common primary brain tumour, is reported here. This study genotyped the single nucleotide polymorphism (SNP) rs78378222 in 566 glioma cases and 603 controls. The variant 'C' allele (with an allelic frequency of 1.1% in controls) was associated with a 3.5-fold excess in glioma risk (odds ratio 3.54; p=0.0001). Variant carriers had significantly improved survival (hazard ratio 0.52; p=0.009) when compared to non-carriers. The rs78378222 SNP is the first confirmed rare susceptibility variant in glioma. Results may shed light on the aetiology and progression of these tumours. | Alleles, Case-Control Studies, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genotype, Glioma, Heterozygote, Humans, Odds Ratio, Polymorphism, Single Nucleotide, Reproducibility of Results, Risk Factors, Tumor Suppressor Protein p53 | null |
22,706,369 | 2015-02-26 | 2012-06-18 | 1120-9763 | Epidemiologia e prevenzione | [Campaign «Asbestos free»]. | Berrino Franco, Bai Edoardo | ita | null | Journal Article | Asbestos | IM | 22706369, 1342 | null | Asbestos, Construction Materials, Electric Wiring, Environmental Exposure, Female, Geological Phenomena, Health Promotion, Humans, Italy, Lung Neoplasms, Male, Mesothelioma, Occupational Diseases, Occupational Exposure, Pleural Neoplasms, Solar Energy | null |
22,706,379 | 2012-10-24 | 2012-07-03 | 1477-9234 | Dalton transactions (Cambridge, England : 2003) | Structural characterization and spectroelectrochemical, anion sensing and solvent dependence photophysical studies of a bimetallic Ru(II) complex derived from 1,3-di(1H-imidazo[4,5-f][1,10]phenanthroline-2-yl)benzene. | Saha Debasish, Das Shyamal, Mardanya Sourav, Baitalik Sujoy | eng | null | Journal Article | null | null | 22706379, 10.1039/c2dt30633f | The X-ray crystal structure of a mixed-ligand bimetallic ruthenium(II) complex of composition [(bipy)(2)Ru(H(2)Impib)Ru(bipy)(2)](ClO(4))(4) (1), where H(2)Impib = 1,3-di(1H-imidazo[4,5-f][1,10]phenanthroline-2-yl)benzene and bipy = 2,2'-bipyridine, has been determined and showed that the compound crystallized in monoclinic form with the space group P2(1)/c. The absorption, steady state and time-resolved luminescence spectral properties of the complex were thoroughly investigated in different solvents. The compound displays strong luminescence at room temperature with lifetimes in the range of 140-470 ns, depending upon the nature of the solvent. Solvent-induced lifetime tuning makes the complex a suitable solvatochromic probe. The complex is found to undergo one simultaneous two-electron reversible oxidation in the positive potential window (0 to +1.6 V) and four quasi-reversible reductions in the negative potential window (0 to -2.2 V). Spectroelectrochemical studies have also been carried out for the bimetallic compound in the range of 300-1600 nm. With stepwise oxidation of the Ru(ii) centers replacement of MLCT bands by LMCT bands occur with the development of a broad band at λ(max) = 1260 nm, which is ascribed to inter-valence charge-transfer (IVCT) transition for the mixed-valence Ru(II)Ru(III) species. The anion sensing properties of the receptor were thoroughly investigated in acetonitrile solution using absorption, steady state and time-resolved emission spectroscopic studies. The anion sensing studies revealed that the receptor acts as sensor for F(-), AcO(-) and H(2)PO(4)(-). It is evident that in the presence of excess F(-) and AcO(-) ions, deprotonation of the imidazole N-H fragments of the receptor occurs, an event which is signaled by the change of color from yellow to orange visible to the naked eye. From the absorption and emission titration studies the binding/equilibrium constants of the receptor with the anions have also been determined. Anion-induced lifetime quenching by F(-) and AcO(-) and enhancement by H(2)PO(4)(-) makes the receptor a suitable lifetime-based sensor for selective anions. Cyclic voltammetry (CV) measurements of the compound carried out in acetonitrile have provided evidence in favor of anion-dependent electrochemical responses with F(-) and AcO(-) ions. | null | null |
22,706,364 | 2015-02-26 | 2012-06-18 | 1120-9763 | Epidemiologia e prevenzione | [Incidence of stomach cancer is decreasing faster in the Centre-North of Italy]. | Castaing Marine, Bella Francesca, Buzzoni Carlotta | ita | null | Journal Article | null | IM | 22706364, 1327 | null | Female, Humans, Incidence, Italy, Male, Morbidity, Stomach Neoplasms | null |
22,706,367 | 2015-02-26 | 2015-07-08 | 1120-9763 | Epidemiologia e prevenzione | [Climate change and communicable diseases]. | Vineis Paolo | ita | null | Journal Article | Water | IM | 22706367, 1340 | null | Adaptation, Physiological, Animals, Climate Change, Communicable Diseases, Disease Vectors, Ecosystem, Global Health, Humans, Parasites, Viruses, Water, Water Microbiology | null |
22,706,380 | 2013-01-23 | 2024-04-26 | 1432-0851 | Cancer immunology, immunotherapy : CII | Involvement of eosinophils in the anti-tumor response. | Gatault Solène, Legrand Fanny, Delbeke Marie, Loiseau Sylvie, Capron Monique | eng | null | Journal Article, Review | null | IM | 22706380, 10.1007/s00262-012-1288-3, PMC11029779, 8386711, 8896393, 1501242, 10756213, 16968820, 18384431, 18671772, 14982507, 18195069, 16617160, 9495201, 19794066, 21643739, 2919183, 7035499, 17371978, 10194423, 1636093, 1618895, 9258955, 18978205, 12566422, 19536290, 16551246, 15270732, 18395252, 21682744, 22174445, 12147093, 20012860, 1890265, 12100059, 12920442, 9680344, 16619553, 14629326, 20065995, 21657821, 20447076, 16076292, 15611233, 21068403, 15508524, 17198080, 6850611, 8114916, 10666192, 16395696, 12672048, 10738211, 11893453, 9816049, 12028296, 15908052 | Eosinophils have long been associated with allergy and parasitic infections. Today, they are considered as multifunctional leukocytes, which participate both in innate and adaptive immune response though the expression of various receptors and mediators. Although the tumor-associated eosinophilia is observed for a long time in many hematological and solid malignancies, with a generally good prognosis value, there is a lack of knowledge on the different mechanisms involved in this phenomenon. Moreover, the recent discovery in human eosinophils of different receptors and mediators, shared with lymphocytes and involved in anti-tumor defense, suggests that eosinophils can play a role in anti-tumoral immunity. We review in the present paper the current knowledge on epidemiology, recruitment, and mechanisms involved in the response of eosinophils toward tumors. | Adaptive Immunity, Animals, Eosinophils, Humans, Immunity, Innate, Neoplasms | null |
22,706,382 | 2012-10-19 | 2013-11-21 | 1463-9084 | Physical chemistry chemical physics : PCCP | DFT study of the fragmentation mechanism of uracil RNA base. | Arani Leila Sadr, Mignon Pierre, Abdoul-Carime Hassan, Farizon Bernadette, Farizon Michel, Chermette Henry | eng | null | Journal Article | Uracil, RNA | IM | 22706382, 10.1039/c2cp40384f | The fragmentation process of the uracil RNA base has been investigated via DFT calculations in order to assign fragments to the ionisation mass spectrum obtained after dissociation induced by collision experiments. The analysis of the electronic distribution and geometry parameters of the cation allows selection of several bonds that may be cleaved and lead to the formation of various fragments. Differences are observed in the electronic behaviour of the bond breaking as well as the energy required for the cleavage. It is reported that N(3)-C(4) and N(1)-C(2) bonds are more easily cleaved than the C(5)-C(6) bond, since the corresponding energy barriers amount to ΔG = +1.627, +1.710, +5.459 eV, respectively, which makes the C(5)-C(6) bond cleavage almost prohibited. Among all possible formed fragments, the formation of the OCN(+) fragment for the peak at m/z = 42 Da is excluded because of an intermediate that was not observed experimentally and too a large free energy barrier. Based on the required free energy, it is observed that two fragment derivatives: C(2)H(4)N(+) and C(2)H(2)O˙(+) may be formed, with a small preference for C(2)H(4)N(+). This latter product is not formed through a retro Diels Alder reaction in contrast to C(2)H(2)O˙(+). The following sequence is proposed for the peak at 42 Da: C(2)H(4)N(+) (from N(1)-C(2), C(4)-C(5) cleavages) > C(2)H(2)O˙(+) (from N(3)-C(4), N(1)-C(2) and C(5)-C(6) cleavages) > C(2)H(4)N(+) (from N(1)-C(2), N(3)-C(4) and C(4)-C(5)) > C(2)H(2)O˙(+) (from C(5)-C(6), N(1)-C(2) and N(3)-C(4) cleavages) > NCO(+) (from N(1)-C(2), C(4)-C(5) and N(3)-C(4) cleavages). Finally the peak at 28 Da is assigned to CNH(2)(+) derivatives that can be formed through two different paths, the easiest one requiring 5.4 eV. | Mass Spectrometry, Quantum Theory, RNA, Uracil | null |
22,706,381 | 2013-01-04 | 2024-04-26 | 1432-0851 | Cancer immunology, immunotherapy : CII | DNA and adenovirus tumor vaccine expressing truncated survivin generates specific immune responses and anti-tumor effects in a murine melanoma model. | Zhang Haihong, Wang Yuqian, Liu Chenlu, Zhang Lixing, Xia Qiu, Zhang Yong, Wu Jiaxin, Jiang Chunlai, Chen Yan, Wu Yongge, Zha Xiao, Yu Xianghui, Kong Wei | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Adjuvants, Immunologic, Antigens, Neoplasm, Antineoplastic Agents, BIRC5 protein, human, Cancer Vaccines, IL2 protein, human, Inhibitor of Apoptosis Proteins, Interleukin-2, Survivin, Vaccines, DNA, Carboplatin | IM | 22706381, 10.1007/s00262-012-1296-3, PMC11028718, 19526360, 18486759, 19027133, 10587640, 19294381, 11221872, 10932241, 11069302, 15779886, 10496530, 7816645, 17471164, 10594755, 17933439, 21296855, 15553667, 20623510, 10876248, 10949039, 15761255, 16482569, 17196504, 16446167, 16026775, 18075512, 11507035, 15695399, 16019131, 20429791, 20211203, 18286284, 20960189, 17509725, 21143701, 21371173, 14695157, 15193151, 22205930, 11149963, 21211062, 21573500 | Survivin is overexpressed in major types of cancer and is considered an ideal "universal" tumor-associated antigen that can be targeted by immunotherapeutic vaccines. However, its anti-apoptosis function raises certain safety concerns. Here, a new truncated human survivin, devoid of the anti-apoptosis function, was generated as a candidate tumor vaccine. Interleukin 2 (IL-2) has been widely used as an adjuvant for vaccination against various diseases. Meanwhile, the DNA prime and recombinant adenovirus (rAd) boost heterologous immunization strategy has been proven to be highly effective in enhancing immune responses. Therefore, the efficacy of a new cancer vaccine based on a truncated form of survivin, combined with IL-2, DNA prime, and rAd boost, was tested. As prophylaxis, immunization with the DNA vaccine alone resulted in a weak immune response and modest anti-tumor effect, whereas the tumor inhibition ratio with the DNA vaccine administered with IL-2 increased to 89 % and was further increased to nearly 100 % by rAd boosting. Moreover, complete tumor rejection was observed in 5 of 15 mice. Efficacy of the vaccine administered therapeutically was enhanced by nearly 300 % when combined with carboplatin. These results indicated that vaccination with a truncated survivin vaccine using DNA prime-rAd boost combined with IL-2 adjuvant and carboplatin represents an attractive strategy to overcoming immune tolerance to tumors and has potential therapeutic benefits in melanoma cancer. | Adenoviridae, Adjuvants, Immunologic, Animals, Antigens, Neoplasm, Antineoplastic Agents, Cancer Vaccines, Carboplatin, Cell Line, Tumor, Combined Modality Therapy, Female, Humans, Inhibitor of Apoptosis Proteins, Interleukin-2, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Mutation, Skin Neoplasms, Survivin, Treatment Outcome, Vaccines, DNA | null |
22,706,383 | 2013-01-10 | 2014-11-20 | 1098-8823 | Prostaglandins & other lipid mediators | Lipidic last breath of life in patients with alcoholic liver disease. | Raszeja-Wyszomirska Joanna, Safranow Krzysztof, Milkiewicz Małgorzata, Milkiewicz Piotr, Szynkowska Agnieszka, Stachowska Ewa | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Fatty Acids, Unsaturated, Hydroxyeicosatetraenoic Acids, hydroxyoctadecadienoic acid, Lipoxygenases | IM | 22706383, S1098-8823(12)00071-8, 10.1016/j.prostaglandins.2012.06.001 | Alcoholic liver disease (ALD) begins with the accumulation of lipid droplets in the liver. Lipids which accumulate in the liver can stimulate inflammation, and the fatty acid derivatives, hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic acids (HODEs), may play an important role in this process. We evaluated the concentrations of linoleic and arachidonic acid derivatives in the plasma of patients with ALD, non-alcoholic fatty liver disease (NAFLD) and healthy individuals. The groups consisted of 173 subjects: 63 patients with ALD, 90 with NAFLD and 20 healthy volunteers. Plasma 12-, 15-, and 5-HETE as well as 9- and 13-HODE were assessed using HPLC and isoprostane 8-epi-PGF 2α III was evaluated with an ELISA. In addition the mRNA expression of lipoxygenases (5-LOX, 15-LOX-1, 15-LOX-2) in the liver samples of patients with ALD cirrhosis was measured. A significant difference between the plasma concentrations of the analyzed derivatives was found when divided according to gender. The most significant differences were found between healthy individuals and ALD patients, as well as ALD and NAFLD individuals regardless of gender. The increased plasma HODEs and HETEs concentrations were in line with the increase in 5- and 15-LOX-1 and 15-LOX-2 mRNA in liver samples from ALD cirrhosis patients. LOXs expression and peroxidation of polyunsaturated fatty acids by free radical-propagated chemical oxidation may be contributing factors in liver necroinflammatory injury in ALD. | Adult, Aged, Fatty Acids, Unsaturated, Fatty Liver, Female, Humans, Hydroxyeicosatetraenoic Acids, Lipid Peroxidation, Lipoxygenases, Liver, Liver Cirrhosis, Alcoholic, Liver Diseases, Alcoholic, Male, Middle Aged, Non-alcoholic Fatty Liver Disease | null |
22,706,384 | 2012-11-08 | 2021-10-21 | 1757-9708 | Integrative biology : quantitative biosciences from nano to macro | DEFOG: discrete enrichment of functionally organized genes. | Wittkop Tobias, Berman Ari E, Fleisch K Mathew, Mooney Sean D | eng | RL9 AG032114 (NIA NIH HHS, United States); UL1DE019608 (NIDCR NIH HHS, United States); U54 HG004028 (NHGRI NIH HHS, United States); RL9AG032114 (NIA NIH HHS, United States); R01 LM009722 (NLM NIH HHS, United States); U54-HG004028 (NHGRI NIH HHS, United States); UL1 DE019608 (NIDCR NIH HHS, United States); T32 AG000266 (NIA NIH HHS, United States); T32-AG000266 (NIA NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural | null | IM | 22706384, 10.1039/c2ib00136e, PMC3469163, NIHMS386620, 21149340, 21216273, 19131956, 21179468, 21372810, 17353930, 19897547, 21097893, 20556492, 17032457, 17646325, 18487275, 15642094, 15956674, 19601769, 10582567, 20656902, 18927115, 20490702, 16680138, 21651979, 21615982, 21115458, 20508635, 18988627, 10802651, 17941985, 18986374, 21067998, 19850723, 19269181, 21171977, 20576703, 16547200, 21045057, 21179020, 15972284, 21530648, 19909260, 14512350, 21447597, 17672901, 21496570, 11917018, 21071413, 18511468, 21592412, 19380743, 15657099, 20170730, 12525261, 18613948, 21587205 | High-throughput biological experiments commonly result in a list of genes or proteins of interest. In order to understand the observed changes of the genes and to generate new hypotheses, one needs to understand the functions and roles of the genes and how those functions relate to the experimental conditions. Typically, statistical tests are performed in order to detect enriched Gene Ontology categories or pathways, i.e. the categories are observed in the genes of interest more often than is expected by chance. Depending on the number of genes and the complexity and quantity of functions in which they are involved, such an analysis can easily result in hundreds of enriched terms. To this end we developed DEFOG, a web-based application that facilitates the functional analysis of gene sets by hierarchically organizing the genes into functionally related modules. Our computational pipeline utilizes three powerful tools to achieve this goal: (1) GeneMANIA creates a functional consensus network of the genes of interest based on gene-list-specific data fusion of hundreds of genomic networks from publicly available sources; (2) Transitivity Clustering organizes those genes into a clear hierarchy of functionally related groups, and (3) Ontologizer performs a Gene Ontology enrichment analysis on the resulting gene clusters. DEFOG integrates this computational pipeline within an easy-to-use web interface, thus allowing for a novel visual analysis of gene sets that aids in the discovery of potentially important biological mechanisms and facilitates the creation of new hypotheses. DEFOG is available at http://www.mooneygroup.org/defog. | Aging, Algorithms, Animals, Cluster Analysis, Computational Biology, Computer Graphics, Databases, Genetic, Gene Expression Profiling, Gene Regulatory Networks, Genomics, Humans, Internet, Multigene Family, Oligonucleotide Array Sequence Analysis, Software | null |
22,706,385 | 2012-09-19 | 2024-06-10 | 1546-170X | Nature medicine | Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity. | Zeissig Sebastian, Murata Kazumoto, Sweet Lindsay, Publicover Jean, Hu Zongyi, Kaser Arthur, Bosse Esther, Iqbal Jahangir, Hussain M Mahmood, Balschun Katharina, Röcken Christoph, Arlt Alexander, Günther Rainer, Hampe Jochen, Schreiber Stefan, Baron Jody L, Moody D Branch, Liang T Jake, Blumberg Richard S | eng | R37 DK044319 (NIDDK NIH HHS, United States); DK51362 (NIDDK NIH HHS, United States); DK44319 (NIDDK NIH HHS, United States); R01 DK051362 (NIDDK NIH HHS, United States); R01 AI068090 (NIAID NIH HHS, United States); DK034854 (NIDDK NIH HHS, United States); R01 DK046900 (NIDDK NIH HHS, United States); P30 DK034854 (NIDDK NIH HHS, United States); DK88199 (NIDDK NIH HHS, United States); AR048632 (NIAMS NIH HHS, United States); R01 DK044319 (NIDDK NIH HHS, United States); AI049313 (NIAID NIH HHS, United States); R01 DK088199 (NIDDK NIH HHS, United States); ZIA DK054500-16 (Intramural NIH HHS, United States); R01 DK053056 (NIDDK NIH HHS, United States); P30 DK026743 (NIDDK NIH HHS, United States); ZIA DK054500-14 (Intramural NIH HHS, United States); AI068090 (NIAID NIH HHS, United States); R29 DK046900 (NIDDK NIH HHS, United States); P 21530 (Austrian Science Fund FWF, Austria); R01 DK093646 (NIDDK NIH HHS, United States); ZIA DK054500-15 (Intramural NIH HHS, United States); DK46900 (NIDDK NIH HHS, United States); R56 DK046900 (NIDDK NIH HHS, United States); R01 AI049313 (NIAID NIH HHS, United States); R01 AR048632 (NIAMS NIH HHS, United States); DK53056 (NIDDK NIH HHS, United States); R56 DK053056 (NIDDK NIH HHS, United States); DK026743 (NIDDK NIH HHS, United States) | Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't | Antigens, CD1d, Biomarkers, Carrier Proteins, Hepatitis B Surface Antigens, Lysophospholipids, lysophosphatidylethanolamine, microsomal triglyceride transfer protein, Interferon-gamma, Phospholipases A2, Secretory | IM | 22706385, nm.2811, 10.1038/nm.2811, PMC3478098, NIHMS411188, 18596101, 10225972, 9020080, 18624350, 12477811, 19201769, 14578883, 8838795, 15306601, 21393863, 15721363, 15197224, 20367794, 17991774, 19075267, 11050064, 22121032, 16188494, 17312112, 16087713, 12493258, 20592474, 18039107, 19859526, 9867845, 17312007, 14530376, 1473153, 15377291, 17150027, 12874260, 3477814, 15522818, 9374462, 7560864, 13428781, 2169517, 15100412, 11333892, 15107843, 11970881, 16603549, 16627542, 11520464, 19415116, 18347010, 10714687, 11015434, 21555485, 17487145, 10221919, 19866614 | In most adult humans, hepatitis B is a self-limiting disease leading to life-long protective immunity, which is the consequence of a robust adaptive immune response occurring weeks after hepatitis B virus (HBV) infection. Notably, HBV-specific T cells can be detected shortly after infection, but the mechanisms underlying this early immune priming and its consequences for subsequent control of viral replication are poorly understood. Using primary human and mouse hepatocytes and mouse models of transgenic and adenoviral HBV expression, we show that HBV-expressing hepatocytes produce endoplasmic reticulum (ER)-associated endogenous antigenic lipids including lysophospholipids that are generated by HBV-induced secretory phospholipases and that lead to activation of natural killer T (NKT) cells. The absence of NKT cells or CD1d or a defect in ER-associated transfer of lipids onto CD1d results in diminished HBV-specific T and B cell responses and delayed viral control in mice. NKT cells may therefore contribute to control of HBV infection through sensing of HBV-induced modified self-lipids. | Adaptive Immunity, Adenoviridae, Animals, Antigens, CD1d, Biomarkers, Carrier Proteins, Coculture Techniques, Hepatitis B Surface Antigens, Hepatitis B virus, Hepatitis B, Chronic, Hepatocytes, Humans, Immunity, Interferon-gamma, Lipid Metabolism, Lymphocyte Activation, Lysophospholipids, Lysosomes, Mice, Natural Killer T-Cells, Phospholipases A2, Secretory | null |
22,706,386 | 2012-09-19 | 2021-10-21 | 1546-170X | Nature medicine | Therapy of Pelizaeus-Merzbacher disease in mice by feeding a cholesterol-enriched diet. | Saher Gesine, Rudolphi Fabian, Corthals Kristina, Ruhwedel Torben, Schmidt Karl-Friedrich, Löwel Siegrid, Dibaj Payam, Barrette Benoit, Möbius Wiebke, Nave Klaus-Armin | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Cholesterol, Dietary, RNA, Messenger | IM | 22706386, nm.2833, 10.1038/nm.2833, 19837175, 20091761, 16306428, 17115121, 18647169, 7512350, 9772185, 19416638, 10586248, 18555697, 12810827, 18485258, 11956232, 17133418, 17487163, 19171898, 15557474, 9590558, 11748293, 20456004, 19439587, 19077110, 20629189, 9150132, 8520726, 14764421, 17786222, 19455583, 8987820, 15793579, 11018060, 11276118, 11309501, 19474101, 21846724, 11238557 | Duplication of PLP1 (proteolipid protein gene 1) and the subsequent overexpression of the myelin protein PLP (also known as DM20) in oligodendrocytes is the most frequent cause of Pelizaeus-Merzbacher disease (PMD), a fatal leukodystrophy without therapeutic options. PLP binds cholesterol and is contained within membrane lipid raft microdomains. Cholesterol availability is the rate-limiting factor of central nervous system myelin synthesis. Transgenic mice with extra copies of the Plp1 gene are accurate models of PMD. Dysmyelination followed by demyelination, secondary inflammation and axon damage contribute to the severe motor impairment in these mice. The finding that in Plp1-transgenic oligodendrocytes, PLP and cholesterol accumulate in late endosomes and lysosomes (endo/lysosomes), prompted us to further investigate the role of cholesterol in PMD. Here we show that cholesterol itself promotes normal PLP trafficking and that dietary cholesterol influences PMD pathology. In a preclinical trial, PMD mice were fed a cholesterol-enriched diet. This restored oligodendrocyte numbers and ameliorated intracellular PLP accumulation. Moreover, myelin content increased, inflammation and gliosis were reduced and motor defects improved. Even after onset of clinical symptoms, cholesterol treatment prevented disease progression. Dietary cholesterol did not reduce Plp1 overexpression but facilitated incorporation of PLP into myelin membranes. These findings may have implications for therapeutic interventions in patients with PMD. | Animals, Cholesterol, Dietary, Feeding Behavior, Gene Expression Regulation, Mice, Myelin Sheath, Oligodendroglia, Optic Nerve, Pelizaeus-Merzbacher Disease, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Spinal Cord, Subcellular Fractions, Time Factors | null |
22,706,387 | 2012-10-12 | 2018-12-01 | 1473-5598 | Journal of hypertension | Reporting blood pressure effects of antihypertensive treatment in scientific papers: are guidelines needed? | Mancia Giuseppe | eng | null | Editorial, Comment | Antihypertensive Agents | IM | 22706387, 10.1097/HJH.0b013e3283546784, 00004872-201207000-00005 | null | Antihypertensive Agents, Blood Pressure, Humans, Hypertension, Randomized Controlled Trials as Topic | null |
22,706,388 | 2012-10-12 | 2018-12-01 | 1473-5598 | Journal of hypertension | Physical activity, fitness and mortality. | Fagard Robert H | eng | null | Editorial, Comment | null | IM | 22706388, 10.1097/HJH.0b013e3283551eb2, 00004872-201207000-00006 | null | Blood Pressure, Exercise, Humans, Hypertension | null |
22,706,389 | 2012-10-12 | 2018-12-01 | 1473-5598 | Journal of hypertension | Sleep patterns and high blood pressure: more evidence needed. | Lombardi Carolina, Bilo Grzegorz, Parati Gianfranco | eng | null | Editorial, Comment | null | IM | 22706389, 10.1097/HJH.0b013e3283559867, 00004872-201207000-00007 | null | Female, Humans, Hypertension, Male, Primary Health Care, Sleep | null |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.