Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Inverse remodelling algorithm identifies habitual manual activities of primates based on metacarpal bone architecture

Previously, a micro-finite element (micro-FE)-based inverse remodelling method was presented in the literature that reconstructs the loading history of a bone based on its architecture alone. Despite promising preliminary results, it remains unclear whether this method is sensitive enough to detect differences of bone loading related to pathologies or habitual activities. The goal of this study was to test the sensitivity of the inverse remodelling method by predicting joint loading histories of metacarpal bones of species with similar anatomy but clearly distinct habitual hand use. Three groups of habitual hand use were defined using the most representative primate species: manipulation (human), suspensory locomotion (orangutan), and knuckle-walking locomotion (bonobo, chimpanzee, gorilla). Nine to ten micro-computed tomography scans of each species ( n=48 in total) were used to create micro-FE models of the metacarpal head region. The most probable joint loading history was predicted by optimally scaling six load cases representing joint postures ranging from −75∘ (extension) to +75∘ (flexion). Predicted mean joint load directions were significantly different between knuckle-walking and non-knuckle-walking groups ( p<0.05 ) and in line with expected primary hand postures. Mean joint load magnitudes tended to be larger in species using their hands for locomotion compared to species using them for manipulation. In conclusion, this study shows that the micro-FE-based inverse remodelling method is sensitive enough to detect differences of joint loading related to habitual manual activities of primates and might, therefore, be useful for palaeoanthropologists to reconstruct the behaviour of extinct species and for biomedical applications such as detecting pathological joint loading

Calling where it counts:Subordinate pied babblers target the audience of their vocal advertisements

For territorial group-living species, opportunities to reproduce on the natal territory can be limited by a number of factors including the availability of resources within a territory, access to unrelated individuals, and monopolies on reproduction by dominant group members. Individuals looking to reproduce are therefore faced with the options of either waiting for a breeding opportunity to arise in the natal territory, or searching for reproductive opportunities in non-natal groups. In the cooperatively breeding Southern pied babbler, Turdoides bicolor, most individuals who achieve reproductive success do so through taking up dominant breeding positions within non-natal groups. For subordinate pied babblers therefore, searching for breeding opportunities in non-natal groups is of primary importance as this represents the major route to reproductive success. However, prospecting (where individuals leave the group to search for reproductive opportunities within other groups) is costly and individuals rapidly lose weight when not part of a group. Here we demonstrate that subordinate pied babblers adopt an alternative strategy for mate attraction by vocal advertisement from within their natal territories. We show that subordinates focus their calling efforts on the edges of their territory, and specifically near boundaries with neighbouring groups that have potential breeding partners (unrelated individuals of the opposite sex). In contrast to prospecting, calling individuals showed no body mass loss associated with this behaviour, suggesting that calling from within the group may provide a 'cheap' advertisement strategy. Additionally, we show that subordinates use information regarding the composition of neighbouring groups to target the greatest number of potential mating partners

High-latitude marginal reefs support fewer but bigger corals than their tropical counterparts

FC is supported by the Panorama Doctoral Training Partnership (NE/S007458/1), the University of Hull and a JSPS London short-term pre-doctoral fellowship (PE22726). We acknowledge funding from the Australian Research Council Centre of Excellence for Environmental Decisions (CE110001014), an EU Marie Skłodowska-Curie Fellowship (TRIM-DLV-747102), and a Winifred Violet Scott Estate grant to MB; a CSIRO top-up scholarship, an Australian Research Council Discovery Early Career Research Award (DE230100141), a University of Sydney Fellowship and a Chancellor's Postdoctoral Research Fellowship from the University of Technology Sydney to BS. Fieldwork was further supported by two Australian Research Council Centre of Excellence awards (CE0561435 and CE140100020) to JMP and others.Anthropogenic impacts are typically detrimental to tropical coral reefs, but the effect of increasing environmental stress and variability on the size structure of coral communities remains poorly understood. This limits our ability to effectively conserve coral reef ecosystems because size specific dynamics are rarely incorporated. Our aim is to quantify variation in the size structure of coral populations across 20 sites along a tropical-to-subtropical environmental gradient on the east coast of Australia (~ 23 to 30°S), to determine how size structure changes with a gradient of sea surface temperature, turbidity, productivity and light levels. We use two approaches: 1) linear regression with summary statistics (such as median size) as response variables, a method frequently favoured by ecologists and 2) compositional functional regression, a novel method using entire size?frequency distributions as response variables. We then predict coral population size structure with increasing environmental stress and variability. Together, we find fewer but larger coral colonies in marginal reefs, where conditions are typically more variable and stressful, than in tropical reefs. Our model predicts that coral populations may become gradually dominated by larger colonies (> 148 cm2) with increasing environmental stress. Fewer but bigger corals suggest low survival of smaller corals, slow growth, and/or poor recruitment. This finding is concerning for the future of coral reefs, as it implies that current marginal populations, or future reefs in increasingly stressful environmental conditions may have low recovery potential. We highlight the importance of continuously monitoring changes to population structure over biogeographic scales.Publisher PDFPeer reviewe

Long-term outcomes (beyond 5 years) of liver transplant recipients - a transatlantic multicentre study

ABSTRACTThe long-term (>5 year) outcomes following liver transplantation (LT) have not been extensively reported. The aim was to evaluate outcomes of LT recipients who have survived the first 5 years. A multicentre retrospective analysis of prospectively collected data from 3 high volume LT centres (Dallas-USA, Birmingham-UK, and Barcelona-Spain) was undertaken. All adult patients, who underwent LT since the inception of the programme to 31 December 2010, and survived at least 5 years since their LT were included. Patient survival was the primary outcome. A total of 3682 patients who survived at least 5 years following LT (long-term survivors) were included. Overall, median age at LT was 52 years (IQR 44–58); 53.1% were males; and 84.6% were Caucasians. 49.4% (n=1820) died during a follow-up period of 36828 person-years (mean follow-up 10 years). 80.2% (n=1460) of all deaths were premature deaths. Age-standardised all-cause mortality as compared to general population was 3 times higher for males and 5 times higher for females. On adjusted analysis, besides older recipients and older donors, predictors of long-term mortality were malignancy, CVD and dialysis. Implementation of strategies such as non-invasive cancer screening, minimising immunosuppression and intensive primary/secondary cardiovascular prevention could further improve survival

Long-term outcomes (beyond 5 years) of liver transplant recipients - a transatlantic multicentre study

The long-term (>5 year) outcomes following liver transplantation (LT) have not been extensively reported. The aim was to evaluate outcomes of LT recipients who have survived the first 5 years. A multicentre retrospective analysis of prospectively collected data from 3 high volume LT centres (Dallas-USA, Birmingham-UK, and Barcelona-Spain) was undertaken. All adult patients, who underwent LT since the inception of the programme to 31 December 2010, and survived at least 5 years since their LT were included. Patient survival was the primary outcome. A total of 3682 patients who survived at least 5 years following LT (long-term survivors) were included. Overall, median age at LT was 52 years (IQR 44–58); 53.1% were males; and 84.6% were Caucasians. 49.4% (n=1820) died during a follow-up period of 36828 person-years (mean follow-up 10 years). 80.2% (n=1460) of all deaths were premature deaths. Age-standardised all-cause mortality as compared to general population was 3 times higher for males and 5 times higher for females. On adjusted analysis, besides older recipients and older donors, predictors of long-term mortality were malignancy, CVD and dialysis. Implementation of strategies such as non-invasive cancer screening, minimising immunosuppression and intensive primary/secondary cardiovascular prevention could further improve survival

ERRATUM: “Versailles project on advanced materials and standards interlaboratory study on intensity calibration for x-ray photoelectron spectroscopy instruments using low-density polyethylene” [J. Vac. Sci. Technol. A 38, 063208 (2020)]

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