排序方式: 共有45条查询结果,搜索用时 78 毫秒
21.
Introduction
Both cardiovascular disease and osteoporosis are important causes of morbidity and mortality in the elderly. The co-occurrence of cardiovascular disease and osteoporosis prompted us to review the evidence of an association between cardiovascular (CV) disease and osteoporosis and potential shared common pathophysiological mechanisms. 相似文献22.
HD iPSC Consortium 《Cell Stem Cell》2012,11(2):264-278
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. Here, The HD Consortium reports the generation and characterization of 14 induced pluripotent stem cell (iPSC) lines from HD patients and controls. Microarray profiling revealed CAG-repeat-expansion-associated gene expression patterns that distinguish patient lines from controls, and early onset versus late onset HD. Differentiated HD neural cells showed disease-associated changes in electrophysiology, metabolism, cell adhesion, and ultimately cell death for lines with both medium and longer CAG repeat expansions. The longer repeat lines were however the most vulnerable to cellular stressors and BDNF withdrawal, as assessed using a range of assays across consortium laboratories. The HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a human stem cell platform for screening new candidate therapeutics. 相似文献
23.
A haplotype map of allohexaploid wheat reveals distinct patterns of selection on homoeologous genomes 总被引:1,自引:0,他引:1
Katherine W Jordan Shichen Wang Yanni Lun Laura-Jayne Gardiner Ron MacLachlan Pierre Hucl Krysta Wiebe Debbie Wong Kerrie L Forrest IWGS Consortium Andrew G Sharpe Christine HD Sidebottom Neil Hall Christopher Toomajian Timothy Close Jorge Dubcovsky Alina Akhunova Luther Talbert Urmil K Bansal Harbans S Bariana Matthew J Hayden Curtis Pozniak Jeffrey A Jeddeloh Anthony Hall Eduard Akhunov 《Genome biology》2015,16(1)
BackgroundBread wheat is an allopolyploid species with a large, highly repetitive genome. To investigate the impact of selection on variants distributed among homoeologous wheat genomes and to build a foundation for understanding genotype-phenotype relationships, we performed population-scale re-sequencing of a diverse panel of wheat lines.ResultsA sample of 62 diverse lines was re-sequenced using the whole exome capture and genotyping-by-sequencing approaches. We describe the allele frequency, functional significance, and chromosomal distribution of 1.57 million single nucleotide polymorphisms and 161,719 small indels. Our results suggest that duplicated homoeologous genes are under purifying selection. We find contrasting patterns of variation and inter-variant associations among wheat genomes; this, in addition to demographic factors, could be explained by differences in the effect of directional selection on duplicated homoeologs. Only a small fraction of the homoeologous regions harboring selected variants overlapped among the wheat genomes in any given wheat line. These selected regions are enriched for loci associated with agronomic traits detected in genome-wide association studies.ConclusionsEvidence suggests that directional selection in allopolyploids rarely acted on multiple parallel advantageous mutations across homoeologous regions, likely indicating that a fitness benefit could be obtained by a mutation at any one of the homoeologs. Additional advantageous variants in other homoelogs probably either contributed little benefit, or were unavailable in populations subjected to directional selection. We hypothesize that allopolyploidy may have increased the likelihood of beneficial allele recovery by broadening the set of possible selection targets.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0606-4) contains supplementary material, which is available to authorized users. 相似文献24.
Malika Delobel-Ayoub Virginie Ehlinger Dana Klapouszczak Thierry Maffre Jean-Philippe Raynaud Cyrille Delpierre Catherine Arnaud 《PloS one》2015,10(11)
Background and Objectives
Study of the impact of socioeconomic status on autism spectrum disorders (ASD) and severe intellectual disabilities (ID) has yielded conflicting results. Recent European studies suggested that, unlike reports from the United States, low socioeconomic status is associated with an increased risk of ASD. For intellectual disabilities, the links with socioeconomic status vary according to the severity. We wished to clarify the links between socioeconomic status and the prevalence of ASD (with or without ID) and isolated severe ID.Methods
500 children with ASD and 245 children with severe ID (IQ <50) aged 8 years, born 1995 to 2004, were recruited from a French population-based registry. Inclusions were based on clinical diagnoses reported in medical records according to the International Classification of Diseases, 10th Revision. Socioeconomic status was measured by indicators available at block census level which characterize the population of the child’s area of residence. Measures of deprivation, employment, occupation, education, immigration and family structure were used. Prevalences were compared between groups of census units defined by the tertiles of socioeconomic level in the general population.Results
Prevalence of ASD with associated ID was higher in areas with the highest level of deprivation and the highest percentage of unemployed adults, persons with no diploma, immigrants and single-parent families. No association was found when using occupational class. Regarding ASD without associated ID, a higher prevalence was found in areas with the highest percentage of immigrants. No association was found for other socioeconomic indicators. The prevalence of isolated severe ID was likely to be higher in the most disadvantaged groups defined by all indicators.Conclusion
The prevalence of ASD with associated ID and of severe isolated ID is more likely to be higher in areas with the highest level of deprivation. 相似文献25.
Gretchen S. Ehlinger Richard A. Tankersley 《Journal of experimental marine biology and ecology》2006,337(2):205-214
The American horseshoe crab, Limulus polyphemus (Linnaeus), typically inhabits estuaries and coastal areas with pronounced semi-diurnal and diurnal tides that are used to synchronize the timing of spawning, larval hatching, and emergence. Horseshoe crabs spawn in the intertidal zone of sandy beaches and larval emergence occurs when the larvae exit the sediments and enter the plankton. However, L. polyphemus populations also occur in areas that lack significant tidal changes and associated synchronization cues. Endogenous activity rhythms that match predictable environmental cycles may enable larval horseshoe crabs to time swimming activity to prevent stranding on the beach. To determine if L. polyphemus larvae possess a circatidal rhythm in vertical swimming, larvae collected from beach nests and the plankton were placed under constant conditions and their activity monitored for 72 h. Time-series analyses of the activity records revealed a circatidal rhythm with a free-running period of ≈ 12.5 h. Maximum swimming activity consistently occurred during the time of expected falling tides, which may serve to reduce the chance of larvae being stranded on the beach and aid in seaward transport by ebb currents (i.e., ebb-tide transport). To determine if agitation serves as the entrainment cue, larvae were shaken on a 12.4 h cycle to simulate conditions during high tide in areas with semi-diurnal tides. When placed under constant conditions, larval swimming increased near the expected times of agitation. Thus, endogenous rhythms of swimming activity of L. polyphemus larvae in both tidal and nontidal systems may help synchronize swimming activity with periods of high water and inundation. 相似文献
26.
Bodo Brand Anja Hartmann Dirk Repsilber Bettina Griesbeck-Zilch Olga Wellnitz Christa Kühn Siriluck Ponsuksili Heinrich HD Meyer Manfred Schwerin 《遗传、选种与进化》2011,43(1):24
Background
During the past ten years many quantitative trait loci (QTL) affecting mastitis incidence and mastitis related traits like somatic cell score (SCS) were identified in cattle. However, little is known about the molecular architecture of QTL affecting mastitis susceptibility and the underlying physiological mechanisms and genes causing mastitis susceptibility. Here, a genome-wide expression analysis was conducted to analyze molecular mechanisms of mastitis susceptibility that are affected by a specific QTL for SCS on Bos taurus autosome 18 (BTA18). Thereby, some first insights were sought into the genetically determined mechanisms of mammary gland epithelial cells influencing the course of infection.Methods
Primary bovine mammary gland epithelial cells (pbMEC) were sampled from the udder parenchyma of cows selected for high and low mastitis susceptibility by applying a marker-assisted selection strategy considering QTL and molecular marker information of a confirmed QTL for SCS in the telomeric region of BTA18. The cells were cultured and subsequently inoculated with heat-inactivated mastitis pathogens Escherichia coli and Staphylococcus aureus, respectively. After 1, 6 and 24 h, the cells were harvested and analyzed using the microarray expression chip technology to identify differences in mRNA expression profiles attributed to genetic predisposition, inoculation and cell culture.Results
Comparative analysis of co-expression profiles clearly showed a faster and stronger response after pathogen challenge in pbMEC from less susceptible animals that inherited the favorable QTL allele ''Q'' than in pbMEC from more susceptible animals that inherited the unfavorable QTL allele ''q''. Furthermore, the results highlighted RELB as a functional and positional candidate gene and related non-canonical Nf-kappaB signaling as a functional mechanism affected by the QTL. However, in both groups, inoculation resulted in up-regulation of genes associated with the Ingenuity pathways ''dendritic cell maturation'' and ''acute phase response signaling'', whereas cell culture affected biological processes involved in ''cellular development''.Conclusions
The results indicate that the complex expression profiling of pathogen challenged pbMEC sampled from cows inheriting alternative QTL alleles is suitable to study genetically determined molecular mechanisms of mastitis susceptibility in mammary epithelial cells in vitro and to highlight the most likely functional pathways and candidate genes underlying the QTL effect. 相似文献27.
28.
Abstract All life-history stages of the Australian Podonominae (Chironomidae) genus Archaeochlus Brundin are revised, providing evidence for recognition of a separate clade, named here as Austrochlus Cranston. Based on molecular and morphological evidence, the clade contains two additional species: Austrochlus parabrundini Cranston, Edward and Cook sp. n. is described from Western Australia where its granite outcrop seepage habitat and geographical range is almost identical to that of the type species Austrochlus brundini Cranston, Edward and Colless (n. comb); Austrochlus centralaustralis Cranston, Edward and Cook sp. n. is described from ephemeral seepage/flows in the MacDonnell and James Ranges of central Australia. Molecular studies reported here confirm species distinctions, relationships to African taxa, and basal relationships within the Chironomidae. Modelled distributions provide evidence for range restriction by seasonal rainfall patterns. 相似文献
29.
Thomas A. Guilliam Stanislaw K. Jozwiakowski Aaron Ehlinger Ryan P. Barnes Sean G. Rudd Laura J. Bailey J. Mark Skehel Kristin A. Eckert Walter J. Chazin Aidan J. Doherty 《Nucleic acids research》2015,43(2):1056-1068
PrimPol is a recently identified polymerase involved in eukaryotic DNA damage tolerance, employed in both re-priming and translesion synthesis mechanisms to bypass nuclear and mitochondrial DNA lesions. In this report, we investigate how the enzymatic activities of human PrimPol are regulated. We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and does not interact with it in vivo. We identify that PrimPol interacts with both of the major single-strand binding proteins, RPA and mtSSB in vivo. Using NMR spectroscopy, we characterize the domains responsible for the PrimPol-RPA interaction, revealing that PrimPol binds directly to the N-terminal domain of RPA70. In contrast to the established role of SSBs in stimulating replicative polymerases, we find that SSBs significantly limit the primase and polymerase activities of PrimPol. To identify the requirement for this regulation, we employed two forward mutation assays to characterize PrimPol''s replication fidelity. We find that PrimPol is a mutagenic polymerase, with a unique error specificity that is highly biased towards insertion-deletion errors. Given the error-prone disposition of PrimPol, we propose a mechanism whereby SSBs greatly restrict the contribution of this enzyme to DNA replication at stalled forks, thus reducing the mutagenic potential of PrimPol during genome replication. 相似文献
30.
The objective of this study was to determine whether obesity prevalence and weight-related behaviors (e.g., diet, physical activity) differ among students enrolled in 2-year community/technical colleges and those attending 4-year colleges/universities. This information could inform the development of intervention strategies. Through an existing surveillance system of Minnesota postsecondary education institutions, survey data were collected from 16,539 students from 27 campuses (14 two-year college campuses, 13 four-year college/university campuses; 2007-2008), including self-reported physical activity, media use, dietary patterns, weight control behaviors, height, and weight. Unadjusted analyses indicated that students enrolled in 2-year colleges, particularly females, had a higher prevalence of overweight/obesity, lower levels of physical activity, more television viewing, higher intakes of soda, fast food, and diet pills compared to students attending 4-year colleges (P < 0.05). Females attending 4-year colleges were more likely to engage in certain unhealthy weight control behaviors (taking diet pills, binge eating, self-induced vomiting) compared to females attending 2-year institutions. Among male students there were fewer differences between 2-year and 4-year colleges. Controlling for sociodemographic factors (e.g., race/ethnicity, age), most disparities in prevalence estimates remained, though many were attenuated. Overall, few young adults engage in weight-related behaviors consistent with national recommendations. Two-year college students may represent a particularly at-risk group. Disparities between 2- and 4-year college students exist beyond the sociodemographic differences in these populations. Effective weight-related interventions are needed for young adults, particularly females attending 2-year colleges and all males attending postsecondary institutions. 相似文献