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61.
N'Diaye A Chen GK Palmer CD Ge B Tayo B Mathias RA Ding J Nalls MA Adeyemo A Adoue V Ambrosone CB Atwood L Bandera EV Becker LC Berndt SI Bernstein L Blot WJ Boerwinkle E Britton A Casey G Chanock SJ Demerath E Deming SL Diver WR Fox C Harris TB Hernandez DG Hu JJ Ingles SA John EM Johnson C Keating B Kittles RA Kolonel LN Kritchevsky SB Le Marchand L Lohman K Liu J Millikan RC Murphy A Musani S Neslund-Dudas C North KE Nyante S Ogunniyi A Ostrander EA Papanicolaou G Patel S Pettaway CA 《PLoS genetics》2011,7(10):e1002298
Adult height is a classic polygenic trait of high heritability (h
2 ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ∼10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10−12 and 2p14-rs4315565, P = 1.2×10−8). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10−4 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits. 相似文献
62.
Christian Burri Patrick D. Yeramian James L. Allen Ada Merolle Kazadi Kyanza Serge Alain Mpanya Pascal Lutumba Victor Kande Betu Ku Mesu Constantin Miaka Mia Bilenge Jean-Pierre Fina Lubaki Alfred Mpoo Mpoto Mark Thompson Blaise Fungula Munungu Francisco Manuel Théophilo Josenando Sonja C. Bernhard Carol A. Olson Johannes Blum Richard R. Tidwell Gabriele Pohlig 《PLoS neglected tropical diseases》2016,10(2)
Background
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.Methods
The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.Findings/Conclusion
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3. 相似文献63.
64.
Sonja Maria Hansen Hilde Haider Alexandra Eichler Claudia Godau Peter A. Frensch Robert Gaschler 《PloS one》2015,10(11)
How can we enhance the understanding of abstract mathematical principles in
elementary school? Different studies found out that nonsymbolic estimation could
foster subsequent exact number processing and simple arithmetic. Taking the
commutativity principle as a test case, we investigated if the approximate
calculation of symbolic commutative quantities can also alter the access to
procedural and conceptual knowledge of a more abstract arithmetic principle.
Experiment 1 tested first graders who had not been instructed about
commutativity in school yet. Approximate calculation with symbolic quantities
positively influenced the use of commutativity-based shortcuts in formal
arithmetic. We replicated this finding with older first graders (Experiment 2) and third graders (Experiment 3). Despite the positive
effect of approximation on the spontaneous application of commutativity-based
shortcuts in arithmetic problems, we found no comparable impact on the
application of conceptual knowledge of the commutativity principle. Overall, our
results show that the usage of a specific arithmetic principle can benefit from
approximation. However, the findings also suggest that the correct use of
certain procedures does not always imply conceptual understanding. Rather, the
conceptual understanding of commutativity seems to lag behind procedural
proficiency during elementary school. 相似文献
65.
Camiel L. M. de Roij van Zuijdewijn Muriel P. C. Grooteman Michiel L. Bots Peter J. Blankestijn Sonja Steppan Janine Büchel Rolf H. H. Groenwold Vincent Brandenburg Marinus A. van den Dorpel Piet M. ter Wee Menso J. Nubé Marc G. Vervloet 《PloS one》2015,10(11)
Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a post-hoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77–94), the HR for cardiovascular mortality 0.73 (95% CI 0.62–0.85) and for sudden death 0.76 (95% CI 0.62–0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ -0.011 mmol/L/year, 95% CI -0.017 to -0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time. 相似文献
66.
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68.
Alexis Díaz-Vegas Cristian A. Campos Ariel Contreras-Ferrat Mariana Casas Sonja Buvinic Enrique Jaimovich Alejandra Espinosa 《PloS one》2015,10(6)
During exercise, skeletal muscle produces reactive oxygen species (ROS) via NADPH oxidase (NOX2) while inducing cellular adaptations associated with contractile activity. The signals involved in this mechanism are still a matter of study. ATP is released from skeletal muscle during electrical stimulation and can autocrinely signal through purinergic receptors; we searched for an influence of this signal in ROS production. The aim of this work was to characterize ROS production induced by electrical stimulation and extracellular ATP. ROS production was measured using two alternative probes; chloromethyl-2,7- dichlorodihydrofluorescein diacetate or electroporation to express the hydrogen peroxide-sensitive protein Hyper. Electrical stimulation (ES) triggered a transient ROS increase in muscle fibers which was mimicked by extracellular ATP and was prevented by both carbenoxolone and suramin; antagonists of pannexin channel and purinergic receptors respectively. In addition, transient ROS increase was prevented by apyrase, an ecto-nucleotidase. MRS2365, a P2Y1 receptor agonist, induced a large signal while UTPyS (P2Y2 agonist) elicited a much smaller signal, similar to the one seen when using ATP plus MRS2179, an antagonist of P2Y1. Protein kinase C (PKC) inhibitors also blocked ES-induced ROS production. Our results indicate that physiological levels of electrical stimulation induce ROS production in skeletal muscle cells through release of extracellular ATP and activation of P2Y1 receptors. Use of selective NOX2 and PKC inhibitors suggests that ROS production induced by ES or extracellular ATP is mediated by NOX2 activated by PKC. 相似文献
69.
Irene Monika Hfliger Sonja Hofstetter Thomas Mock Manuela Hanna Stettler Mireille Meylan Kemal Mehinagic Nadine Stokar‐Regenscheit Cord Drgemüller 《Animal genetics》2019,50(4):372-375
In 2015, cholesterol deficiency (CD) was reported for the first time as a new recessive defect in Holstein cattle. After GWAS mapping and identification of a disease‐associated haplotype, a causative loss‐of‐function variant in APOB was identified. CD‐clinically affected APOB homozygotes showed poor development, intermittent diarrhea and hypocholesterolemia and, consequently, a limited life expectation. Herein, we present a collection of 18 cases clinically diagnosed as CD‐affected APOB heterozygotes. CD‐clinically affected heterozygotes show reduced cholesterol and triglyceride blood concentrations. The differences in total blood cholesterol and triglycerides between nine CD‐clinically affected and 36 non‐affected heterozygotes were significant. As only some APOB heterozygotes show the clinical CD phenotype, we assume that the penetrance is reduced in heterozygotes compared to the fully penetrant effect observed in homozygotes. We conclude that APOB‐associated CD represents most likely an incomplete dominant inherited metabolic disease with incomplete penetrance in heterozygotes. 相似文献
70.
Food Biophysics - The stabilization of interfaces with mixed emulsifiers composed of natural ingredients is of increasing interest in order to modulate stability of food colloids. To this purpose,... 相似文献