1,541 research outputs found

    Meta-analysis identifies pleiotropic loci controlling phenotypic trade-offs in sorghum

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    Community association populations are composed of phenotypically and genetically diverse accessions. Once these populations are genotyped, the resulting marker data can be reused by different groups investigating the genetic basis of different traits. Because the same genotypes are observed and scored for a wide range of traits in different environments, these populations represent a unique resource to investigate pleiotropy. Here, we assembled a set of 234 separate trait datasets for the Sorghum Association Panel, a group of 406 sorghum genotypes widely employed by the sorghum genetics community. Comparison of genome-wide association studies (GWAS) conducted with two independently generated marker sets for this population demonstrate that existing genetic marker sets do not saturate the genome and likely capture only 35–43% of potentially detectable loci controlling variation for traits scored in this population. While limited evidence for pleiotropy was apparent in cross-GWAS comparisons, a multivariate adaptive shrinkage approach recovered both known pleiotropic effects of existing loci and new pleiotropic effects, particularly significant impacts of known dwarfing genes on root architecture. In addition, we identified new loci with pleiotropic effects consistent with known trade-offs in sorghum development. These results demonstrate the potential for mining existing trait datasets from widely used community association populations to enable new discoveries from existing trait datasets as new, denser genetic marker datasets are generated for existing community association populations

    The recent mediccal treatment of hepatocellular carcinoma in our hospital

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    Septins are a family of 14 cytoskeletal proteins that dynamically form hetero-oligomers and organize membrane microdomains for protein complexes. The previously reported interactions withSNAREproteins suggested the involvement of septins in exocytosis. However, the contradictory results of up- or down-regulation of septin-5 in various cells and mouse models or septin-4 in mice suggested either an inhibitory or a stimulatory role for these septins in exocytosis. The involvement of the ubiquitously expressed septin-2 or general septin polymerization in exocytosis has not been explored to date. Here, by nano-LC with tandem MS and immunoblot analyses of the sep-tin-2 interactome in mouse brain, we identified not only SNARE proteins but also Munc-18-1 (stabilizes assembled SNARE complexes), N-ethylmaleimide-sensitive factor (NSF) (disassembles SNARE complexes after each membrane fusion event), and the chaperones Hsc70 and synucleins (maintain functional conformation of SNARE proteins after complex disassembly). Importantly, α-soluble NSF attachment protein (SNAP), the adaptor protein that mediates NSF binding to the SNARE complex, did not interact with septin-2, indicating that septins undergo reorganization during each exocytosis cycle. Partial depletion of septin-2 by siRNA or impairment of septin dynamics by forchlorfenuron inhibited constitutive and stimulated exocytosis of secreted and transmembrane proteins in various cell types. Forchlorfenuron impaired the interaction between SNAP-25 and its chaperone Hsc70, decreasing SNAP-25 levels in cultured neuroendocrine cells, and inhibited both spontaneous and stimulated acetylcholine secretion in mouse motor neurons. The results demonstrate a stimulatory role of septin-2 and the dynamic reorganization of septin oligomers in exocytosis

    Septin dynamics are essential for exocytosis

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    Septins are a family of 14 cytoskeletal proteins that dynamically form hetero-oligomers and organize membrane microdomains for protein complexes. The previously reported interactions withSNAREproteins suggested the involvement of septins in exocytosis. However, the contradictory results of up- or down-regulation of septin-5 in various cells and mouse models or septin-4 in mice suggested either an inhibitory or a stimulatory role for these septins in exocytosis. The involvement of the ubiquitously expressed septin-2 or general septin polymerization in exocytosis has not been explored to date. Here, by nano-LC with tandem MS and immunoblot analyses of the sep-tin-2 interactome in mouse brain, we identified not only SNARE proteins but also Munc-18-1 (stabilizes assembled SNARE complexes), N-ethylmaleimide-sensitive factor (NSF) (disassembles SNARE complexes after each membrane fusion event), and the chaperones Hsc70 and synucleins (maintain functional conformation of SNARE proteins after complex disassembly). Importantly, α-soluble NSF attachment protein (SNAP), the adaptor protein that mediates NSF binding to the SNARE complex, did not interact with septin-2, indicating that septins undergo reorganization during each exocytosis cycle. Partial depletion of septin-2 by siRNA or impairment of septin dynamics by forchlorfenuron inhibited constitutive and stimulated exocytosis of secreted and transmembrane proteins in various cell types. Forchlorfenuron impaired the interaction between SNAP-25 and its chaperone Hsc70, decreasing SNAP-25 levels in cultured neuroendocrine cells, and inhibited both spontaneous and stimulated acetylcholine secretion in mouse motor neurons. The results demonstrate a stimulatory role of septin-2 and the dynamic reorganization of septin oligomers in exocytosis

    Dissimilar Impact of a Mediterranean Diet and Physical Activity on Anthropometric Indices: A Cross-Sectional Study from the ILERVAS Project

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    There is a close relationship between lifestyle behaviors and excess adiposity. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. However, little is known about the impact of physical activity and adherence to a Mediterranean diet on these indices. Here we report the results of a cross-sectional study with 6672 middle-aged subjects with low to moderate cardiovascular risk from the Ilerda Vascular (ILERVAS) project. The participants' adherence to physical activity (International Physical Activity Questionnaire short form) and MedDiet (Mediterranean Diet Adherence Screener) was evaluated. Measures of total adiposity (BMI, Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), and Deurenberg's formula), central adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora's equation, A body adiposity index, and body roundness index), and lean body mass (Hume formula) were assessed. Irrespective of sex, lower indices of physical activity were associated with higher values of total body fat and central adiposity. This result was constant regardless of the indices used to estimate adiposity. However, the association between MedDiet and obesity indices was much less marked and more dependent on sex than that observed for physical activity. Lean body mass was influenced by neither physical activity nor MedDiet adherence. No joint effect between physical activity and MedDiet to lower estimated total or central adiposity indices was shown. In conclusion, physical activity is related to lower obesity indices in a large cohort of middle-aged subjects. MedDiet showed a slight impact on estimated anthropometric indices, with no joint effect when considering both lifestyle variables

    Reduction in the Incidence of Type 2 Diabetes With the Mediterranean Diet: Results of the PREDIMED-Reus nutrition intervention randomized trial

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    OBJECTIVE - To test the effects of two Mediterranean diet (MedDiet) interventions versus a low-fat diet on incidence of diabetes. RESEARCH DESIGN AND METHODS - This was a three-arm randomized trial in 418 nondiabetic subjects aged 55-80 years recruited in one center (PREDIMED-Reus, northeastern Spain) of the Prevención con Dieta Mediterránea [PREDIMED] study, a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk. Participants were randomly assigned to education on a low-fat diet (control group) or to one of two MedDiets, supplemented with either free virgin olive oil (1 liter/week) or nuts (30 g/day). Diets were ad libitum, and no advice on physical activity was given. The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria. RESULTS - After a median follow-up of 4.0 years, diabetes incidence was 10.1% (95% CI 5.1-15.1), 11.0% (5.9 -16.1), and 17.9% (11.4 -24.4) in the MedDiet with olive oil group, the MedDiet with nuts group, and the control group, respectively. Multivariable adjusted hazard ratios of diabetes were 0.49 (0.25- 0.97) and 0.48 (0.24-0.96) in the MedDiet supplemented with olive oil and nuts groups, respectively, compared with the control group. When the two MedDiet groups were pooled and compared with the control group, diabetes incidence was reduced by 52% (27- 86). In all study arms, increased adherence to the MedDiet was inversely associated with diabetes incidence. Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity. CONCLUSIONS - MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk. © 2011 by the American Diabetes Association.This study was funded, in part, by the Spanish Ministry of Health (Instituto de Salud Carlos III) (projects PI051839, PI070240, PI1001407, G03/140, and RD06/0045), Fondo Europeo de Desarrollo Regional, and the Public Health Division of the Department of Health of the Autonomous Government of Catalonia in collaboration with Merck Sharp & Dohme. The Fundación Patrimonio Comunal Olivarero and Hojiblanca SA (Málaga, Spain), California Walnut Commission (Sacramento, CA), Borges SA (Reus, Spain), and Morella Nuts SA (Reus, Spain) donated the olive oil, walnuts, almonds, and hazelnuts, respectively, used in the study.Peer Reviewe

    Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial

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    BackgroundProspective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person.MethodsWe evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED (‘PREvención con DIeta MEDiterránea’) study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality.ResultsDuring a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend 3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts >3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66).ConclusionsIncreased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk.Please see related commentary: http://www.biomedcentral.com/1741-7015/11/165.Trial registrationClinicaltrials.gov. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005

    Differential contribution of the m7G-cap to the 5′ end-dependent translation initiation of mammalian mRNAs

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    Many mammalian mRNAs possess long 5′ UTRs with numerous stem-loop structures. For some of them, the presence of Internal Ribosome Entry Sites (IRESes) was suggested to explain their significant activity, especially when cap-dependent translation is compromised. To test this hypothesis, we have compared the translation initiation efficiencies of some cellular 5′ UTRs reported to have IRES-activity with those lacking IRES-elements in RNA-transfected cells and cell-free systems. Unlike viral IRESes, the tested 5′ UTRs with so-called ‘cellular IRESes’ demonstrate only background activities when placed in the intercistronic position of dicistronic RNAs. In contrast, they are very active in the monocistronic context and the cap is indispensable for their activities. Surprisingly, in cultured cells or cytoplasmic extracts both the level of stimulation with the cap and the overall translation activity do not correlate with the cumulative energy of the secondary structure of the tested 5′ UTRs. The cap positive effect is still observed under profound inhibition of translation with eIF4E-BP1 but its magnitude varies for individual 5′ UTRs irrespective of the cumulative energy of their secondary structures. Thus, it is not mandatory to invoke the IRES hypothesis, at least for some mRNAs, to explain their preferential translation when eIF4E is partially inactivated
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