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821.
Anna L. Mitchell Anette B?e Wolff Katie MacArthur Jolanta U. Weaver Bijay Vaidya Sophie Bensing on behalf of The Swedish Addison Registry Study Group Martina M. Erichsen Rebecca Darlay Eystein S. Husebye Heather J. Cordell Simon H. S. Pearce 《PloS one》2015,10(6)
BackgroundAutoimmune Addison’s disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered.MethodsDNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach.ResultsIn a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene.ConclusionThis linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis. 相似文献
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Maryke Gray Alastair McNeilage Katie Fawcett Martha M. Robbins Benard Ssebide Deo Mbula Prosper Uwingeli 《African Journal of Ecology》2010,48(3):588-599
The mountain gorillas (Gorilla beringei beringei) of the Virunga Volcanoes Range of Rwanda, Uganda, and the Democratic Republic of Congo are one of the most endangered ape populations in the world. Following a dramatic decline during the 1960s, and relative stability in the 1970s, the population steadily increased during the 1980s. Due to political instability and war, a complete census had not been conducted since 1989. Here we compare the results of a complete census using the ‘sweep method’ conducted in 2003 with those from a monitoring program, to estimate the size and distribution of the gorilla population. A total of 360 gorillas were counted from census measurements and known habituated groups. Based on quantitative assessments of the census accuracy, we calculated that an additional 20 gorillas were not counted, leading to an estimated population of 380 individuals, and a 1.15% annual growth rate since 1989. The Ranger Based Monitoring programme yielded similar results. The encouraging results must be viewed with caution, however, because the growth was concentrated almost entirely in one section of the Virungas. Additionally, the distribution of gorilla groups was negatively correlated with the frequency of human disturbances, which highlights the need to continue strengthening conservation efforts. 相似文献
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Caribbean coral reefs have transformed into algal-dominated habitats over the past half-century, but the role of specific anthropogenic drivers is unresolved due to the lack of ecosystem-level data predating human disturbance. To better understand the extent and causes of long-term Caribbean reef declines, we produced a continuous 3000-yr record of the ecosystem state of three reefs in Bocas del Toro, Caribbean Panama. From fossils and sediments obtained from reef matrix cores, we tracked changes in reef accretion rates and the taxonomic and functional group composition of fish, coral, urchin, bivalve and benthic foraminifera. This dataset provided a comprehensive picture of reef community and environmental change. At all sites, reefs shifted from systems with greater relative abundance of herbivorous fish, epifaunal suspension feeding bivalves and Diadema urchins to systems with greater relative abundance of micropredator fish, infaunal bivalves and Echinometra urchins. These transitions were initiated a millennium ago at two less-degraded reefs fringing offshore islands and ~250 yr ago at a degraded patch reef near the continental coast. Ecosystem shifts were accompanied by a decline in reef accretion rates, and at the patch reef, a decline in water quality since the 18th century. Within all cores, synchronous increases in infaunal bivalves and declines in herbivorous fish regardless of water quality suggest a loss of hard substrate and increasingly hypoxic sediment conditions related to herbivore loss. While the early timing of ecosystem transitions at the fringing reefs implicates large-scale hydrological change, the more recent timing of change and loss of water quality at the patch reef implicates terrigenous runoff from land-clearing. Our whole-ecosystem reconstruction reveals that reef ecosystem deterioration appears to follow a predictable trajectory whether driven by natural or anthropogenic disturbances and that historical local human activities have quickly unraveled reefs at a scale similar to longer-term natural environmental change. 相似文献
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Defense strategies against infectious threats can be divided into resistance and tolerance mechanisms. Resistance mechanisms involve reduction of pathogen burden and include many established examples, one of them being the destruction of intracellular pathogens through autophagy (xenophagy). Tolerance mechanisms protect the host from damage caused by the pathogen or the immune response independent of pathogen load. The role of autophagy in maintaining homeostasis in response to environmental stress suggests that this pathway is involved in tolerance to a variety of infectious agents. However, demonstrating that autophagy promotes tolerance independent of its role in resistance has been a challenge, especially during infection by clinically relevant pathogens. We have found that autophagy protects against Staphylococcus aureus infection by maintaining tolerance toward a pore forming toxin secreted by the bacteria, α-toxin. 相似文献
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Substantial Generalization of Sensorimotor Learning from Bilateral to Unilateral Movement Conditions
Controversy exists regarding whether bimanual skill learning can generalize to unimanual performance. For example, some investigators showed that dynamic adaptation could only partially generalize between bilateral and unilateral movement conditions, while others demonstrated complete generalization of visuomotor adaptation. Here, we identified three potential factors that might have contributed to the discrepancy between the two sets of findings. In our first experiment, subjects performed reaching movements toward eight targets bilaterally with a novel force field applied to both arms, then unilaterally with the force field applied to one arm. Results showed that the dynamic adaptation generalized completely from bilateral to unilateral movements. In our second experiment, the same force field was only applied to one arm during both bilateral and unilateral movements. Results indicated complete transfer again. Finally, our subjects performed reaching movements toward a single target with the force field or a novel visuomotor rotation applied only to one arm during both bilateral and unilateral movements. The reduced breadth of experience obtained during bilateral movements resulted in incomplete transfer, which explains previous findings of limited generalization. These findings collectively suggest a substantial overlap between the neural processes underlying bilateral and unilateral movements, supporting the idea that bilateral training, often employed in stroke rehabilitation, is a valid method for improving unilateral performance. However, our findings also suggest that while the neural representations developed during bilateral training can generalize to facilitate unilateral performance, the extent of generalization may depend on the breadth of experience obtained during bilateral training. 相似文献