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Reduction in glutamate clearance, whether induced pharmacologically or associated with a relative decrease of glial coverage in the vicinity of synapses, affected transmitter release through modulation of presynaptic metabotropic glutamate receptors.
Astrocytic wrapping of neurons, therefore, contributes to the regulation of synaptic efficacy in the central nervous system. | scifact_200 |
BACKGROUND The combination of radiotherapy plus long-term medical suppression of androgens (> or = 2 years) improves overall survival in patients with locally advanced prostate cancer.
We compared the use of radiotherapy plus short-term androgen suppression with the use of radiotherapy plus long-term androgen suppression in the treatment of locally advanced prostate cancer. | scifact_201 |
METHODS We randomly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of androgen suppression to two groups, one to receive no further treatment (short-term suppression) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist (long-term suppression). | scifact_202 |
An outcome of noninferiority of short-term androgen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival, with a one-sided alpha level of 0.05.
An interim analysis showed futility, and the results are presented with an adjusted one-sided alpha level of 0.0429. | scifact_203 |
RESULTS A total of 1113 men were registered, of whom 970 were randomly assigned, 483 to short-term suppression and 487 to long-term suppression.
After a median follow-up of 6.4 years, 132 patients in the short-term group and 98 in the long-term group had died; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. | scifact_204 |
The 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively; the observed hazard ratio was 1.42 (upper 95.71% confidence limit, 1.79; P=0.65 for noninferiority).
Adverse events in both groups included fatigue, diminished sexual function, and hot flushes. | scifact_205 |
CONCLUSIONS The combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiotherapy plus 3 years of androgen suppression in the treatment of locally advanced prostate cancer.
(ClinicalTrials.gov number, NCT00003026.) | scifact_206 |
Blind individuals often demonstrate enhanced nonvisual perceptual abilities.
However, the neural substrate that underlies this improved performance remains to be fully understood.
An earlier behavioral study demonstrated that some early-blind people localize sounds more accurately than sighted controls using monaural cues. | scifact_207 |
In order to investigate the neural basis of these behavioral differences in humans, we carried out functional imaging studies using positron emission tomography and a speaker array that permitted pseudo-free-field presentations within the scanner.
During binaural sound localization, a sighted control group showed decreased cerebral blood flow in the occipital lobe, which was not seen in early-blind individuals. | scifact_208 |
During monaural sound localization (one ear plugged), the subgroup of early-blind subjects who were behaviorally superior at sound localization displayed two activation foci in the occipital cortex.
This effect was not seen in blind persons who did not have superior monaural sound localization abilities, nor in sighted individuals.
The degree of activation of one of these foci was strongly correlated with sound localization accuracy across the entire group of blind subjects. | scifact_209 |
The results show that those blind persons who perform better than sighted persons recruit occipital areas to carry out auditory localization under monaural conditions.
We therefore conclude that computations carried out in the occipital cortex specifically underlie the enhanced capacity to use monaural cues. | scifact_210 |
Our findings shed light not only on intermodal compensatory mechanisms, but also on individual differences in these mechanisms and on inhibitory patterns that differ between sighted individuals and those deprived of vision early in life. | scifact_211 |
The tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells and infiltrating immune cells, which may inhibit or promote tumor growth and progression.
The objectives of this retrospective study were to characterize the density of tumor-associated macrophages (TAMs) in breast cancer, and to correlate the density of TAMs with clinicopathological parameters. | scifact_212 |
Paraffin-embedded specimens and clinicopathological data, including up to 5 years follow-up information, were obtained from 172 breast cancer patients.
Immunohistochemical staining for CD68 (marker for macrophages) was performed and evaluated in a blinded fashion.
We found that TAMs were significantly frequent in high histopathological grade breast cancer patients. | scifact_213 |
Breast cancer patients with a high density of TAMs had significantly lower rates of disease-free survival and 5-year overall survival than patients with low density of TAMs.
Furthermore, high-infiltration of TAMs indicated worse survival rate for patients with node-negative breast cancer.
In conclusion, the number of TAMs in the tumor stroma is an independent predictor of survival time for breast cancer patients. | scifact_214 |
High-infiltration of TAMs is a significant unfavorable prognostic factor for patients with invasive breast cancer and, as such, is a potentially useful prognostic marker for breast cancer. | scifact_215 |
Dishevelled (Dvl) proteins are important signaling components of both the canonical beta-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements that produce narrowing and elongation of the tissue.
Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. | scifact_216 |
Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls.
Dvl3(-/-) mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis.
These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+). | scifact_217 |
Although neurulation appeared normal in both Dvl3(-/-) and LtapLp/+ mutants, Dvl3(+/-);LtapLp/+ combined mutants displayed incomplete neural tube closure.
Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2.
More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. | scifact_218 |
Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals.
In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development.
Finally, we establish several developmental processes in which the three Dvls are functionally redundant. | scifact_219 |
The epithelial cadherin (E-cadherin)-catenin complex binds to cytoskeletal components and regulatory and signaling molecules to form a mature adherens junction (AJ).
This dynamic structure physically connects neighboring epithelial cells, couples intercellular adhesive contacts to the cytoskeleton, and helps define each cell's apical-basal axis.
Together these activities coordinate the form, polarity, and function of all cells in an epithelium. | scifact_220 |
Several molecules regulate AJ formation and integrity, including Rho family GTPases and Par polarity proteins.
However, only recently, with the development of live-cell imaging, has the extent to which E-cadherin is actively turned over at junctions begun to be appreciated.
This turnover contributes to junction formation and to the maintenance of epithelial integrity during tissue homeostasis and remodeling. | scifact_221 |
AIMS To analyse the long-term outcome of the largest reported cohort of patients presenting asystole during head-up tilt test. | scifact_222 |
METHODS AND RESULTS Since 1990, 1322 patients with syncope of unknown origin have undergone tilt-table testing.
Of those, 330 patients (24 X 9%) presented an abnormal response (syncope or pre-syncope).
Furthermore, 58 of those patients (17 X 5%) suffered a period of asystole (> or = 3000 ms) during the test.
Asystole (median (interquartile range)) lasted 10 (4, 19 X 2) s (range 3-90). | scifact_223 |
Asystole (median (interquartile range)) lasted 10 (4, 19 X 2) s (range 3-90).
Two different protocols (angles) of tilting (Westminster (60 degrees) n=1124; isoproterenol (80 degrees) n=198)) influenced the time to the syncopal episode (13 (6 X 5, 20 X 5) vs 2 (1, 6 X 5) min, P=0,0005) but not the duration of the asystole. | scifact_224 |
During this period, therapy for asystole featured three different stages: first patients were treated with pacemakers; later drug therapy (metoprolol and/or etilefrine) was recommended; lastly (from 1995), no specific treatment was given.
In a cohort age- and gender-matched study, those patients without were compared to those with asystole in a 2:1 basis.
During 40 X 7 months of follow-up (17 X 7, 66 X 8), 12 patients (20 X 6%) with asystole had syncopal recurrences. | scifact_225 |
Furthermore, 34 patients (28 X 8%) without asystole presented syncopal episodes during a follow-up of 51 X 6 months (29 X 3, 73 X 1) (P=ns).
The Kaplan-Meier analysis in patients with and without asystole showed a mean time free of recurrence of 92 X 6 +/-
6 months vs 82 X 6 +/-
4 X 7 months (P=ns).
The previous number of syncopes had a significant relationship with recurrences (P=0 X 002), but not therapy.
There were no cardiac related deaths. | scifact_226 |
CONCLUSIONS (1) Asystole during head-up tilt test does not imply a malignant outcome and syncope recurrence is low; (2) pacemaker or drug therapy do not significantly influence outcome which correlates to the previous number of syncopal episodes but not to gender, age, asystole occurrence, asystole duration and timing to asystole during head-up tilt test; (3) tilting protocol (angle) might influence time to and incidence of asystole during head-up tilt test. | scifact_227 |
Many questions about the biological activity and availability of small molecules remain inaccessible to investigators who could most benefit from their answers.
To narrow the gap between chemoinformatics and biology, we have developed a suite of ligand annotation, purchasability, target, and biology association tools, incorporated into ZINC and meant for investigators who are not computer specialists. | scifact_228 |
The new version contains over 120 million purchasable "drug-like" compounds--effectively all organic molecules that are for sale--a quarter of which are available for immediate delivery.
ZINC connects purchasable compounds to high-value ones such as metabolites, drugs, natural products, and annotated compounds from the literature.
Compounds may be accessed by the genes for which they are annotated as well as the major and minor target classes to which those genes belong. | scifact_229 |
It offers new analysis tools that are easy for nonspecialists yet with few limitations for experts.
ZINC retains its original 3D roots--all molecules are available in biologically relevant, ready-to-dock formats.
ZINC is freely available at http://zinc15.docking.org. | scifact_230 |
The eukaryotic genome consists of DNA molecules far longer than the cells that contain them.
They reach their greatest compaction during chromosome condensation in mitosis.
This process is aided by condensin, a structural maintenance of chromosomes (SMC) family member.
The spatial organization of mitotic chromosomes and how condensin shapes chromatin architecture are not yet fully understood. | scifact_231 |
Here we use chromosome conformation capture (Hi-C) to study mitotic chromosome condensation in the fission yeast Schizosaccharomyces pombe.
This showed that the interphase landscape characterized by small chromatin domains is replaced by fewer but larger domains in mitosis.
Condensin achieves this by setting up longer-range, intrachromosomal DNA interactions, which compact and individualize chromosomes. | scifact_232 |
At the same time, local chromatin contacts are constrained by condensin, with profound implications for local chromatin function during mitosis.
Our results highlight condensin as a major determinant that changes the chromatin landscape as cells prepare their genomes for cell division. | scifact_233 |
BACKGROUND Under the Revised National Tuberculosis Control Programme of India, patients with new smear-positive pulmonary tuberculosis are treated with a thrice-weekly regimen of antitubercular drugs (2H(3)R(3)Z(3)E(3)/4H(3)R(3) [H isoniazid, R rifampicin, Z pyrazinamide and E ethambutol]) for 6 months.
We conducted a retrospective analysis of the efficacy andtolerability of this regimen under clinical trial conditions in HIV-negative patients with newly diagnosed smear-positive pulmonary tuberculosis. | scifact_234 |
METHODS We retrospectively analysed the data on patients assigned to the control regimen (2H (3)R(3)Z(3)E(3)/4H(3)R(3)) in two clinical trials during 2001-06 at the National Institute for Research in Tuberculosis, Chennai, India. | scifact_235 |
RESULTS Of the 268 patients treated with this regimen, data for efficacy analysis were available for 249.
At the end of treatment, of 249 patients, 238 (96%) had a favourable status.
Treatment failure occurred in the remaining 11: 7 in whom the organisms were initially drug-susceptible and 4 with initial drug resistance.
Of the 238 patients who had a favourable status at the end of treatment, 14 (6%) had recurrence of tuberculosis during the following 24 months. | scifact_236 |
In the intention-to-treat analysis, 245 (94%) of 262 patients had a favourable status at the end of treatment.
Of the 28 patients with initial drug resistance, 24 (86%) had a favourable outcome.
Only 4 of these 24 patients were found to have recurrence of tuberculosis in 2 years of follow-up.
Among the 221 patients initially infected with drug-susceptible organisms, drug resistance did not develop in any of the 7 patients in whom the treatment failed or the 10 who had recurrence of tuberculosis. | scifact_237 |
Further, 5 of the 7 patients in whom the treatment failed continued to excrete drug-susceptible bacilli at 6 months.
Adverse drug reactions were observed in 38 (14%) of the 262 patients.
Only 3 (1.1%) needed a modification in the treatment. | scifact_238 |
CONCLUSION This thrice-weekly 6-month regimen of antitubercular drugs, when administered under full supervision, is associated with a high rate of favourable treatment outcomes in HIV-negative patients with newly diagnosed sputum smearpositive pulmonary tuberculosis.
There are few adverse drug reactions in these patients. | scifact_239 |
Curcumin, a major component of turmeric, has been shown to exhibit anti-oxidant and anti-inflammatory activities.
The present study was performed to determine whether curcumin is efficacious against both collagen-induced arthritis (CIA) in mice and IL-1beta-induced activation in fibroblast-like synoviocytes (FLSs).
DBA/1 mice were immunized with bovine type II collagen (CII) and treated with curcumin every other day for 2weeks after the initial immunization. | scifact_240 |
For arthritis, we evaluated the incidence of disease and used an arthritis index based on paw thickness.
In vitro proliferation of CII- or concanavalin A-induced splenic T cells was examined using IFN-gamma production.
Pro-inflammatory cytokines TNF-alpha and IL-1beta were examined in the mouse ankle joint and serum IgG1 and IgG2a isotypes were analyzed.
The expression levels of prostaglandin E(2) (PGE(2)), cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs) in human FLSs were also determined. | scifact_241 |
The results showed that compared with untreated CIA mice, curcumin-treated mice downregulated clinical arthritis score, the proliferation of splenic T cells, expression levels of TNF-alpha and IL-1beta in the ankle joint, and expression levels of IgG2a in serum.
Additionally, by altering nuclear factor (NF)-kappaB transcription activity in FLSs, curcumin inhibited PGE(2) production, COX-2 expression, and MMP secretion. | scifact_242 |
These results suggest that curcumin can effectively suppress inflammatory response by inhibiting pro-inflammatory mediators and regulating humoral and cellular immune responses. | scifact_243 |
Actions of protein products resulting from alternative splicing of the Igf1 gene have received increasing attention in recent years.
However, the significance and functional relevance of these observations remain poorly defined.
To address functions of IGF-I splice variants, we examined the impact of loss of IGF-IEa and IGF-IEb on the proliferation and differentiation of cultured mouse myoblasts. | scifact_244 |
RNA interference-mediated reductions in total IGF-I, IGF-IEa alone, or IGF-IEb alone had no effect on cell viability in growth medium.
However, cells deficient in total IGF-I or IGF-IEa alone proliferated significantly slower than control cells or cells deficient in IGF-IEb in serum-free media. | scifact_245 |
Simultaneous loss of both or specific loss of either splice variant significantly inhibited myosin heavy chain (MyHC) immunoreactivity by 70-80% (P < 0.01) under differentiation conditions (48 h in 2% horse serum) as determined by Western immunoblotting.
This loss in protein was associated with reduced MyHC isoform mRNAs, because reductions in total IGF-I or IGF-IEa mRNA significantly reduced MyHC mRNAs by approximately 50-75% (P < 0.05). | scifact_246 |
Loss of IGF-IEb also reduced MyHC isoform mRNA significantly, with the exception of Myh7, but to a lesser degree (∼20-40%, P < 0.05).
Provision of mature IGF-I, but not synthetic E peptides, restored Myh3 expression to control levels in cells deficient in IGF-IEa or IGF-IEb.
Collectively, these data suggest that IGF-I splice variants may regulate myoblast differentiation through the actions of mature IGF-I and not the E peptides. | scifact_247 |
BACKGROUND Pleurocidin, a 25-mer antimicrobial peptide (AMP), is known to exert bactericidal activity.
However, the synergistic activity and mechanism(s) of pleurocidin in combination with conventional antibiotics, and the antibiofilm effect of the peptide are poorly understood. | scifact_248 |
METHODS The interaction between pleurocidin and antibiotics was evaluated using checkerboard assay.
To study the mechanism(s) involved in their synergism, we detected hydroxyl radical formation using 3'-(p-hydroxyphenyl) fluorescein, measured the NAD(+)/NADH ratio by NAD(+) cycling assay, observed change in bacterial viability with the hydroxyl radical scavenger thiourea, and investigated cytoplasmic membrane damage using propidium iodide. | scifact_249 |
Also, the antibiofilm effect of pleurocidin was examined with the tissue culture plate method. | scifact_250 |
RESULTS All combinations of pleurocidin and antibiotics showed synergistic interaction against bacterial strains (fractional inhibitory concentration index (FICI)≤0.5) except for Enterococcus faecium treated with a combination of the peptide and ampicillin (FICI=0.75).
We identified that pleurocidin alone and in combinations with antibiotics induced formation of hydroxyl radicals. | scifact_251 |
The oxidative stress was caused by a transient NADH depletion and the addition of thiourea prevented bacterial death, especially in the case of the combined treatment of pleurocidin and ampicillin showing synergisms.
The combination of pleurocidin and erythromycin increased permeability of bacterial cytoplasmic membrane.
Additionally, pleurocidin exhibited a potent inhibitory effect on preformed biofilm of bacterial organisms. | scifact_252 |
In conclusion, pleurocidin synergized with antibiotics through hydroxyl radical formation and membrane-active mechanism, and exerted antibiofilm activity.
GENERAL SIGNIFICANCE The synergistic effect between pleurocidin and antibiotics suggests the AMP is a potential therapeutic agent and adjuvant for antimicrobial chemotherapy. | scifact_253 |
BACKGROUND Pregnant women with mild preexisting renal disease have relatively few complications of pregnancy, but the risks of maternal and obstetrical complications in women with moderate or severe renal insufficiency remain uncertain. | scifact_254 |
METHODS We determined the frequency and types of maternal and obstetrical complications and the outcomes of pregnancy in 67 women with primary renal disease (82 pregnancies).
All the women had initial serum creatinine concentrations of at least 1.4 mg per deciliter (124 mumol per liter) and gestations that continued beyond the first trimester. | scifact_255 |
RESULTS The mean (+/-
SD) serum creatinine concentration increased from 1.9 +/-
0.8 mg per deciliter (168 +/-
71 mumol per liter) in early pregnancy to 2.5 +/-
1.3 mg per deciliter (221 +/-
115 mumol per liter) in the third trimester.
The frequency of hypertension rose from 28 percent at base line to 48 percent in the third trimester, and that of high-grade proteinuria (urinary protein excretion, > 3000 mg per liter) from 23 percent to 41 percent. | scifact_256 |
For the 70 pregnancies (57 women) for which data were available during pregnancy and immediately post partum, pregnancy-related loss of maternal renal function occurred in 43 percent.
Eight of these pregnancies (10 percent of the total) were associated with rapid acceleration of maternal renal insufficiency.
Obstetrical complications included a high rate of preterm delivery (59 percent) and growth retardation (37 percent).
The infant survival rate was 93 percent. | scifact_257 |
CONCLUSIONS Among pregnant women with moderate or severe renal insufficiency, the rates of complications due to worsening renal function, hypertension, and obstetrical complications are increased, but fetal survival is high. | scifact_258 |
OBJECTIVES Calcific aortic valve (AV) disease is known to be an inflammation-related process.
High-mobility group box-1 (HMGB1) protein and Toll-like receptor 4 (TLR4) have been reported to participate in several inflammatory diseases.
The purpose of the present study was to determine whether the HMGB1-TLR4 axis is involved in calcific AV disease, and to evaluate the effect of HMGB1, and its potential mechanisms, on the pro-osteogenic phenotype change of valvular interstitial cells (VICs). | scifact_259 |
METHODS Expression of HMGB1 and TLR4 in human calcific AVs was evaluated using immunohistochemical staining and immunoblotting.
Cultured VICs were used as an in vitro model.
The VICs were stimulated with HMGB1 for analysis, with versus without TLR4 small interfering ribonucleic acid (siRNA), c-Jun N-terminal kinase mitogen-activated protein kinase (JNK MAPK), and nuclear factor kappa-B (NF-κB) inhibitors. | scifact_260 |
RESULTS Enhanced accumulation of HMGB1 and TLR4 was observed in calcific valves.
Moreover, we found that HMGB1 induced high levels of pro-inflammatory cytokine production and promoted the osteoblastic differentiation and calcification of VICs.
In addition, HMGB1 induced phosphorylation of JNK MAPK and NF-κB. However, these effects were markedly suppressed by siRNA silencing of TLR4. | scifact_261 |
In addition, blockade of JNK MAPK and NF-κB phosphorylation prohibited HMGB1-induced production of pro-osteogenic factors, and mineralization of VICs. | scifact_262 |
CONCLUSIONS The HMGB1 protein may promote osteoblastic differentiation and calcification of VICs, through the TLR4-JNK-NF-κB signaling pathway. | scifact_263 |
We describe methods for obtaining a quantitative description of RNA processing at high resolution in budding yeast.
As a model gene expression system, we constructed tetON (for induction studies) and tetOFF (for repression, derepression, and RNA degradation studies) yeast strains with a series of reporter genes integrated in the genome under the control of a tetO7 promoter. | scifact_264 |
Reverse transcription and quantitative real-time-PCR (RT-qPCR) methods were adapted to allow the determination of mRNA abundance as the average number of copies per cell in a population.
Fluorescence in situ hybridization (FISH) measurements of transcript numbers in individual cells validated the RT-qPCR approach for the average copy-number determination despite the broad distribution of transcript levels within a population of cells. | scifact_265 |
In addition, RT-qPCR was used to distinguish the products of the different steps in splicing of the reporter transcripts, and methods were developed to map and quantify 3'-end cleavage and polyadenylation.
This system permits pre-mRNA production, splicing, 3'-end maturation and degradation to be quantitatively monitored with unprecedented kinetic detail, suitable for mathematical modeling. | scifact_266 |
Using this approach, we demonstrate that reporter transcripts are spliced prior to their 3'-end cleavage and polyadenylation, that is, cotranscriptionally. | scifact_267 |
The p75(NTR) neurotrophin receptor has been implicated in multiple biological and pathological processes.
While significant advances have recently been made in understanding the physiologic role of p75(NTR) , many details and aspects remain to be determined.
This is in part because the two existing knockout mouse models (Exons 3 or 4 deleted, respectively), both display features that defy definitive conclusions. | scifact_268 |
Here we describe the generation of mice that carry a conditional p75(NTR) (p75(NTR-FX) ) allele made by flanking Exons 4-6, which encode the transmembrane and all cytoplasmic domains, by loxP sites.
To validate this novel conditional allele, both neural crest-specific p75(NTR) /Wnt1-Cre mutants and conventional p75(NTR) null mutants were generated. | scifact_269 |
Both mutants displayed abnormal hind limb reflexes, implying that loss of p75(NTR) in neural crest-derived cells causes a peripheral neuropathy similar to that seen in conventional p75(NTR) mutants.
This novel conditional p75(NTR) allele will offer new opportunities to investigate the role of p75(NTR) in specific tissues and cells. | scifact_270 |
Abstract Simultaneously evaluating postthaw viability and acrosome integrity of spermatozoa by flow cytometry would provide a valuable testing tool in both research and routine work.
In the present study, a new triple-stain combination was developed for the simultaneous evaluation of viability and acrosome integrity of bovine sperm processed in egg yolk-based extender by flow cytometer. | scifact_271 |
SYBR-14 and propidium iodide (PI) enabled the discrimination of sperm cells from egg yolk and debris particles, which was instrumental for the flow cytometric analyses of frozen-thawed bovine sperm, because it implied that washing steps to remove egg yolk were no longer required.
In addition, phycoerythrin-conjugated peanut agglutinin (PE-PNA) was used to discriminate acrosome-damaged/reacted sperm cells from acrosome-intact cells.
Repeatability was calculated using two processed ejaculates of 10 bulls. | scifact_272 |
Repeatability was calculated using two processed ejaculates of 10 bulls.
Three straws per batch were analyzed in duplicate measurements.
Method-agreement analysis between the SYBR-14/PE-PNA/PI and fluorescein isothiocyanate (FITC)-conjugated PNA was performed, with FITC-PNA/PI staining being carried out on 14 frozen-thawed semen samples immediately after thawing and after a 3-h incubation at 37°C.
The British Standards Institution repeatability index of the SYBR-14/PE-PNA/PI combination was 2.6%. | scifact_273 |
On average, the FITC-PNA/PI method showed a 6.3% overestimation of the live and acrosome-intact sperm cell subpopulation.
In conclusion, the new triple-stain combination is highly repeatable and easy to use in routine application, and it provides a more precise estimate for the rate of sperm cells with intact head membrane and acrosome compared to the generally used and validated FITC-PNA/PI staining. | scifact_274 |
BACKGROUND Roughly 3 million people worldwide were receiving antiretroviral therapy (ART) at the end of 2007, but an estimated 6.7 million were still in need of treatment and a further 2.7 million became infected with HIV in 2007.
Prevention efforts might reduce HIV incidence but are unlikely to eliminate this disease. | scifact_275 |
Prevention efforts might reduce HIV incidence but are unlikely to eliminate this disease.
We investigated a theoretical strategy of universal voluntary HIV testing and immediate treatment with ART, and examined the conditions under which the HIV epidemic could be driven towards elimination. | scifact_276 |
METHODS We used mathematical models to explore the effect on the case reproduction number (stochastic model) and long-term dynamics of the HIV epidemic (deterministic transmission model) of testing all people in our test-case community (aged 15 years and older) for HIV every year and starting people on ART immediately after they are diagnosed HIV positive.
We used data from South Africa as the test case for a generalised epidemic, and assumed that all HIV transmission was heterosexual. | scifact_277 |
FINDINGS The studied strategy could greatly accelerate the transition from the present endemic phase, in which most adults living with HIV are not receiving ART, to an elimination phase, in which most are on ART, within 5 years.
It could reduce HIV incidence and mortality to less than one case per 1000 people per year by 2016, or within 10 years of full implementation of the strategy, and reduce the prevalence of HIV to less than 1% within 50 years. | scifact_278 |
We estimate that in 2032, the yearly cost of the present strategy and the theoretical strategy would both be US$1.7 billion; however, after this time, the cost of the present strategy would continue to increase whereas that of the theoretical strategy would decrease. | scifact_279 |
INTERPRETATION Universal voluntary HIV testing and immediate ART, combined with present prevention approaches, could have a major effect on severe generalised HIV/AIDS epidemics.
This approach merits further mathematical modelling, research, and broad consultation. | scifact_280 |
Hypospadias is a common congenital malformation of the male external genitalia.
We performed a genome-wide association study using pooled DNA from 436 individuals with hypospadias (cases) and 494 controls of European descent and selected the highest ranked SNPs for individual genotyping in the discovery sample, an additional Dutch sample of 133 cases and their parents, and a Swedish series of 266 cases and 402 controls. | scifact_281 |
Individual genotyping of two SNPs (rs1934179 and rs7063116) in DGKK, encoding diacylglycerol kinase κ, produced compelling evidence for association with hypospadias in the discovery sample (allele-specific odds ratio (OR) = 2.5, P = 2.5 × 10−11 and OR = 2.3, P = 2.9 × 10−9, respectively) and in the Dutch (OR = 3.9, P = 2.4 × 10−5 and OR = 3.8, P = 3.4 × 10−5) and Swedish (OR = 2.5, P = 2.6 × 10−8 and OR = 2.2, P = 2.7 × 10−6) replication samples. | scifact_282 |
Expression studies showed expression of DGKK in preputial tissue of cases and controls, which was lower in carriers of the risk allele of rs1934179 (P = 0.047).
We propose DGKK as a major risk gene for hypospadias. | scifact_283 |
UNLABELLED Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors.
In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood.
Here, we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. | scifact_284 |
We show that CD11b(+)/Ly6G(+) neutrophils enhance metastasis formation via two distinct mechanisms.
First, neutrophils inhibit natural killer cell function, which leads to a significant increase in the intraluminal survival time of tumor cells.
Thereafter, neutrophils operate to facilitate extravasation of tumor cells through the secretion of IL1β and matrix metalloproteinases. | scifact_285 |
These results identify neutrophils as key regulators of intraluminal survival and extravasation through their cross-talk with host cells and disseminating carcinoma cells.
SIGNIFICANCE This study provides important insights into the systemic contributions of neutrophils to cancer metastasis by identifying how neutrophils facilitate intermediate steps of the invasion-metastasis cascade.
We demonstrate that neutrophils suppress natural killer cell activity and increase extravasation of tumor cells. | scifact_286 |
Cancer Discov; 6(6); 630-49.
©2016 AACR.This article is highlighted in the In This Issue feature, p. 561. | scifact_287 |
A human placental soluble "high Km" 5'-nucleotidase has been separated from "low Km" 5'-nucleotidase and nonspecific phosphatase by AMP-Sepharose affinity chromatography.
The enzyme was purified 8000-fold to a specific activity of 25.6 mumol/min/mg.
The subunit molecular mass is 53 kDa, and the native molecular mass is 210 kDa, suggesting a tetrameric structure.
Soluble high Km 5'-nucleotidase is most active with IMP and GMP and their deoxy derivatives.
IMP is hydrolyzed 15 times faster than AMP. | scifact_288 |
IMP is hydrolyzed 15 times faster than AMP.
The enzyme has a virtually absolute requirement for magnesium ions and is regulated by them.
Purine nucleoside 5'-triphosphates strongly activate the enzyme with the potency order dATP greater than ATP greater than GTP.
2,3-Diphosphoglycerate activates the enzyme as potently as ATP.
Three millimolar ATP decreased the Km for IMP from 0.33 to 0.09 mM and increased the Vmax 12-fold.
ATP activation was modified by the IMP concentration. | scifact_289 |
ATP activation was modified by the IMP concentration.
At 20 microM IMP the ATP-dependent activation curve was sigmoidal, while at 2 mM IMP it was hyperbolic.
The A0.5 values for ATP were 2.26 and 0.70 mM, and the relative maximal velocities were 32.9 and 126.0 nmol/min, respectively.
Inorganic phosphate shifts the hyperbolic substrate velocity relationship for IMP to a sigmoidal one. | scifact_290 |
With physiological concentrations of cofactors (3 mM ATP, 1-4 mM Pi, 150 mM KCl) at pH 7.4, the enzyme is 25-35 times more active toward 100 microM IMP than 100 microM AMP. | scifact_291 |
These data show that: (a) soluble human placental high Km 5'-nucleotidase coexists in human placenta with the low Km enzyme; (b) under physiological conditions the enzyme favors the hydrolysis of IMP and is critically regulated by IMP, ATP, and Pi levels; and (c) kinetic properties of ATP and IMP are each modified by the other compound suggesting complex interaction of the associated binding sites. | scifact_292 |
In yeast, remodeling of PHO5 promoter chromatin upon activation is accompanied by transient hyperacetylation and subsequent eviction of histones from the promoter in trans.
In the course of rerepression, nucleosomes have to be reassembled on the promoter.
We have analyzed where the histones for reassembly of the inactive promoter chromatin come from. | scifact_293 |
We have analyzed where the histones for reassembly of the inactive promoter chromatin come from.
The use of a strain with two differently tagged and differently regulated versions of histone H3 allowed us to discriminate between histones originating from the chromatin fraction and histones arising from the soluble histone pool.
In this way, we show that the incorporated histones originate from a source in trans. | scifact_294 |
In this way, we show that the incorporated histones originate from a source in trans.
Promoter closure occurs very rapidly, and the histone chaperones Asf1 and Hir1 as well as the SWI/SNF nucleosome remodeling complex appear to be important for rapid reassembly of nucleosomes at the PHO5 promoter. | scifact_295 |
BACKGROUND Few data have evaluated physician adherence to cardiovascular disease (CVD) prevention guidelines according to physician specialty or patient characteristics, particularly gender. | scifact_296 |
METHODS AND RESULTS An online study of 500 randomly selected physicians (300 primary care physicians, 100 obstetricians/gynecologists, and 100 cardiologists) used a standardized questionnaire to assess awareness of, adoption of, and barriers to national CVD prevention guidelines by specialty.
An experimental case study design tested physician accuracy and determinants of CVD risk level assignment and application of guidelines among high-, intermediate-, or low-risk patients. | scifact_297 |
Intermediate-risk women, as assessed by the Framingham risk score, were significantly more likely to be assigned to a lower-risk category by primary care physicians than men with identical risk profiles (P<0.0001), and trends were similar for obstetricians/gynecologists and cardiologists.
Assignment of risk level significantly predicted recommendations for lifestyle and preventive pharmacotherapy. | scifact_298 |
After adjustment for risk assignment, the impact of patient gender on preventive care was not significant except for less aspirin (P<0.01) and more weight management recommended (P<0.04) for intermediate-risk women.
Physicians did not rate themselves as very effective in their ability to help patients prevent CVD.
Fewer than 1 in 5 physicians knew that more women than men die each year from CVD. | scifact_299 |
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