258 research outputs found

    Social bonds provide multiple pathways to reproductive success in wild male chimpanzees

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    In most male mammals, fitness is strongly shaped by competitive access to mates, a non-shareable resource. How, then, did selection favor the evolution of cooperative social bonds? We used behavioral and genetic data on wild chimpanzees (Pan troglodytes schweinfurthii) in Gombe National Park, Tanzania, to study the mechanisms by which male-male social bonds increase reproductive success. Social bonds increased fitness in several ways: first, subordinate males that formed strong bonds with the alpha male had higher siring success. Independently, males with larger networks of strong bonds had higher siring success. In the short term, bonds predicted coalition formation and centrality in the coalition network, suggesting that males benefit from being potential allies to numerous male rivals. In the long term, male ties influenced fitness via improved dominance rank for males that attain alpha status. Together, these results suggest that male bonds evolved in chimpanzees by affording both short- and long-term pathways to reproductive success

    Common Genetic Variants Found in HLA and KIR Immune Genes in Autism Spectrum Disorder

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    The “common variant—common disease” hypothesis was proposed to explain diseases with strong inheritance. This model suggests that a genetic disease is the result of the combination of several common genetic variants. Common genetic variants are described as a 5% frequency differential between diseased vs. matched control populations. This theory was recently supported by an epidemiology paper stating that about 50% of genetic risk for autism resides in common variants. However, rare variants, rather than common variants, have been found in numerous genome wide genetic studies and many have concluded that the “common variant—common disease” hypothesis is incorrect. One interpretation is that rare variants are major contributors to genetic diseases and autism involves the interaction of many rare variants, especially in the brain. It is obvious there is much yet to be learned about autism genetics. Evidence has been mounting over the years indicating immune involvement in autism, particularly the HLA genes on chromosome 6 and KIR genes on chromosome 19. These two large multigene complexes have important immune functions and have been shown to interact to eliminate unwanted virally infected and malignant cells. HLA proteins have important functions in antigen presentation in adaptive immunity and specific epitopes on HLA class I proteins act as cognate ligands for KIR receptors in innate immunity. Data suggests that HLA alleles and KIR activating genes/haplotypes are common variants in different autism populations. For example, class I allele (HLA-A2 and HLA-G 14 bp-indel) frequencies are significantly increased by more than 5% over control populations (Table 2). The HLA-DR4 Class II and shared epitope frequencies are significantly above the control populations (Table 2). Three activating KIR genes: 3DS1, 2DS1, and 2DS2 have increased frequencies of 15, 22, and 14% in autism populations, respectively. There is a 6% increase in total activating KIR genes in autism over control subjects. And, more importantly there is a 12% increase in activating KIR genes and their cognate HLA alleles over control populations (Torres et al., 2012a). These data suggest the interaction of HLA ligand/KIR receptor pairs encoded on two different chromosomes is more significant as a ligand/receptor complex than separately in autism

    Phenotypic characterization of breast cancer: the role of CDC42

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    Purpose: The molecular landscape of breast cancer (BC), especially of the Luminal A subtype, remains to be fully delineated. Transcriptomic data shows that Luminal A tumours are enriched for aberrant expression of genes in the cell division control 42 homolog (CDC42) pathway. This study aims to investigate protein expression of CDC42 in BC and assess its clinicopathological significance. Methods: Expression of CDC42 protein was examined by immunohistochemistry on tissue microarrays in a well characterised cohort of 895 early stage (I-IIIa) primary invasive BCs. Results: CDC42 expression was observed in both the cytoplasm and nucleus of BC cells. High nuclear CDC42 expression demonstrated a significant correlation with ER positive, low-grade tumours and was more common in the lobular histological subtype (all p<0.001). In contrast, cytoplasmic CDC42 showed increased expression in the ductal subtype (p<0.001) and correlated with negative prognostic features such as larger size, higher grade (p<0.05), and higher Ki67 labelling index (p=0.001). Nuclear CDC42 expression was associated with a longer BC specific survival in all cases (p=0.025) and in luminal ER positive tumours (p=0.011). In multivariate analyses including size, grade, lymph node stage and intrinsic subtype, CDC42 was an independent prognostic factor (p=0.032). Conclusion: The results indicate that CDC42 is important molecule in luminal BC, with prognostic significance

    Genome-wide association of functional traits linked with<i> Campylobacter jejuni </i>survival from farm to fork

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    Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, primarily associated with the consumption of contaminated poultry. C. jejuni lineages vary in host range and prevalence in human infection, suggesting differences in survival throughout the poultry processing chain. From 7,343 MLST-characterised isolates, we sequenced 600 C. jejuni and C. coli isolates from various stages of poultry processing and clinical cases. A genome-wide association study (GWAS) in C. jejuni ST-21 and ST-45 complexes identified genetic elements over-represented in clinical isolates that increased in frequency throughout the poultry processing chain. Disease-associated SNPs were distinct in these complexes, sometimes organised in haplotype blocks. The function of genes containing associated elements was investigated, demonstrating roles for cj1377c in formate metabolism, nuoK in aerobic survival and oxidative respiration, and cj1368-70 in nucleotide salvage. This work demonstrates the utility of GWAS for investigating transmission in natural zoonotic pathogen populations and provides evidence that major C. jejuni lineages have distinct genotypes associated with survival, within the host specific niche, from farm to fork. </p

    Ebola Zaire Virus Blocks Type I Interferon Production by Exploiting the Host SUMO Modification Machinery

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    Ebola Zaire virus is highly pathogenic for humans, with case fatality rates approaching 90% in large outbreaks in Africa. The virus replicates in macrophages and dendritic cells (DCs), suppressing production of type I interferons (IFNs) while inducing the release of large quantities of proinflammatory cytokines. Although the viral VP35 protein has been shown to inhibit IFN responses, the mechanism by which it blocks IFN production has not been fully elucidated. We expressed VP35 from a mouse-adapted variant of Ebola Zaire virus in murine DCs by retroviral gene transfer, and tested for IFN transcription upon Newcastle Disease virus (NDV) infection and toll-like receptor signaling. We found that VP35 inhibited IFN transcription in DCs following these stimuli by disabling the activity of IRF7, a transcription factor required for IFN transcription. By yeast two-hybrid screens and coimmunoprecipitation assays, we found that VP35 interacted with IRF7, Ubc9 and PIAS1. The latter two are the host SUMO E2 enzyme and E3 ligase, respectively. VP35, while not itself a SUMO ligase, increased PIAS1-mediated SUMOylation of IRF7, and repressed Ifn transcription. In contrast, VP35 did not interfere with the activation of NF-ÎşB, which is required for induction of many proinflammatory cytokines. Our findings indicate that Ebola Zaire virus exploits the cellular SUMOylation machinery for its advantage and help to explain how the virus overcomes host innate defenses, causing rapidly overwhelming infection to produce a syndrome resembling fulminant septic shock

    Accelerating Haplotype-Based Genome-Wide Association Study Using Perfect Phylogeny and Phase-Known Reference Data

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    The genome-wide association study (GWAS) has become a routine approach for mapping disease risk loci with the advent of large-scale genotyping technologies. Multi-allelic haplotype markers can provide superior power compared with single-SNP markers in mapping disease loci. However, the application of haplotype-based analysis to GWAS is usually bottlenecked by prohibitive time cost for haplotype inference, also known as phasing. In this study, we developed an efficient approach to haplotype-based analysis in GWAS. By using a reference panel, our method accelerated the phasing process and reduced the potential bias generated by unrealistic assumptions in phasing process. The haplotype-based approach delivers great power and no type I error inflation for association studies. With only a medium-size reference panel, phasing error in our method is comparable to the genotyping error afforded by commercial genotyping solutions

    The problem of obesity among adolescents in Hong Kong: a comparison using various diagnostic criteria

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    <p>Abstract</p> <p>Background</p> <p>Obesity is now a global epidemic. In this study, we aimed to assess the rates of obesity using several major diagnostic criteria in Chinese school adolescents in Hong Kong.</p> <p>Methods</p> <p>This is a cross-sectional study. Using a computer-generated coding system, we randomly selected schools from different geographical regions in Hong Kong to obtain a representative sample. Subjects aged 11–18 years of age were randomly selected from different class of the schools. Their rates of obesity according to four different international and local criteria were compared [International Obesity Task Force (IOTF) 2000 criterion; the Group of China Obesity Task Force (COTF) 2004 criterion; Centers for Disease Control and Prevention (CDC) 2000 Growth Charts and the Hong Kong Growth Survey (HKGS) charts in 1993].</p> <p>Results</p> <p>Of the 2098 adolescents [982 (46.8%) boys and 1116 (53.2%) girls], the mean age (± SD) was 15.1 ± 1.8 years (range: 11–18 years; median: 15.0 years). The crude rates of obesity were similar based on IOTF, COTF or CDC criteria (boys: 3.9–6.0%, girls: 1.8–3.7%), however, the rate increased to 11–27% if the HKGS charts were used. Obesity rate varied markedly according to age. It decreased from 8–10% among those aged 12–13 years to 2–4% among those aged 17–18 years.</p> <p>Conclusion</p> <p>The prevalence of obesity in Hong Kong adolescents using various diagnostic criteria were similar except for the 1993 HKGS criteria, which gave an exceeding high figure. Using the IOTF, COTF or CDC criteria, the adolescent obesity in Hong Kong varied from 1.8% to 6.0%.</p

    Evaluation of effectiveness of class-based nutrition intervention on changes in soft drink and milk consumption among young adults

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    <p>Abstract</p> <p>Background</p> <p>During last few decades, soft drink consumption has steadily increased while milk intake has decreased. Excess consumption of soft drinks and low milk intake may pose risks of several diseases such as dental caries, obesity, and osteoporosis. Although beverage consumption habits form during young adulthood, which has a strong impact on beverage choices in later life, nutrition education programs on beverages are scarce in this population. The purpose of this investigation was 1) to assess soft drink and milk consumption and 2) to evaluate the effectiveness of 15-week class-based nutrition intervention in changing beverage choices among college students.</p> <p>Methods</p> <p>A total of 80 college students aged 18 to 24 years who were enrolled in basic nutrition class participated in the study. Three-day dietary records were collected, verified, and analyzed before and after the intervention. Class lectures focused on healthful dietary choices related to prevention of chronic diseases and were combined with interactive hands on activities and dietary feedback.</p> <p>Results</p> <p>Class-based nutrition intervention combining traditional lecture and interactive activities was successful in decreasing soft drink consumption. Total milk consumption, specifically fat free milk, increased in females and male students changed milk choice favoring skim milk over low fat milk. (1% and 2%).</p> <p>Conclusion</p> <p>Class-based nutrition education focusing on prevention of chronic diseases can be an effective strategy in improving both male and female college students' beverage choices. Using this type of intervention in a general nutrition course may be an effective approach to motivate changes in eating behaviors in a college setting.</p
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