190 research outputs found

    Analysis of Fcγ receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B

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    The Fcγ receptors play important roles in the initiation and regulation of many immunological and inflammatory processes, and genetic variants (FCGR) have been associated with numerous autoimmune and infectious diseases. The data in rheumatoid arthritis (RA) are conflicting and we previously demonstrated an association between FCGR3A and RA. In view of the close molecular proximity with FCGR2A, FCGR2B and FCGR3B, additional polymorphisms within these genes and FCGR haplotypes were examined to refine the extent of association with RA. Biallelic polymorphisms in FCGR2A, FCGR2B and FCGR3B were examined for association with RA in two well characterized UK Caucasian and North Indian/Pakistani cohorts, in which FCGR3A genotyping had previously been undertaken. Haplotype frequencies and linkage disequilibrium were estimated across the FCGR locus and a model-free analysis was performed to determine association with RA. This was followed by regression analysis, allowing for phase uncertainty, to identify the particular haplotype(s) that influences disease risk. Our results reveal that FCGR2A, FCGR2B and FCGR3B were not associated with RA. The haplotype with the strongest association with RA susceptibility was the FCGR3A–FCGR3B 158V-NA2 haplotype (odds ratio 3.18, 95% confidence interval 1.13–8.92 [P = 0.03] for homozygotes compared with all genotypes). The association was stronger in the presence of nodules (odds ratio 5.03, 95% confidence interval 1.44–17.56; P = 0.01). This haplotype was also more common in North Indian/Pakistani RA patients than in control individuals, but not significantly so. Logistic regression analyses suggested that FCGR3A remained the most significant gene at this locus. The increased association with an FCGR3A–FCGR3B haplotype suggests that other polymorphic variants within FCGR3A or FCGR3B, or in linkage disequilibrium with this haplotype, may additionally contribute to disease pathogenesis

    An Anglo-Saxon execution cemetery at Walkington Wold, Yorkshire

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    This paper presents a re-evaluation of a cemetery excavated over 30 years ago at Walkington Wold in east Yorkshire. The cemetery is characterized by careless burial on diverse alignments, and by the fact that most of the skeletons did not have associated crania. The cemetery has been variously described as being the result of an early post-Roman massacre, as providing evidence for a ‘Celtic’ head cult or as an Anglo-Saxon execution cemetery. In order to resolve the matter, radiocarbon dates were acquired and a re-examination of the skeletal remains was undertaken. It was confirmed that the cemetery was an Anglo-Saxon execution cemetery, the only known example from northern England, and the site is set into its wider context in the paper

    Nutrition and dementia care: developing an evidence-based model for nutritional care in nursing homes.

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    BACKGROUND: There is a growing volume of research to offer improvements in nutritional care for people with dementia living in nursing homes. Whilst a number of interventions have been identified to support food and drink intake, there has been no systematic research to understand the factors for improving nutritional care from the perspectives of all those delivering care in nursing homes. The aim of this study was to develop a research informed model for understanding the complex nutritional problems associated with eating and drinking for people with dementia. METHODS: We conducted nine focus groups and five semi-structured interviews with those involved or who have a level of responsibility for providing food and drink and nutritional care in nursing homes (nurses, care workers, catering assistants, dietitians, speech and language therapists) and family carers. The resulting conceptual model was developed by eliciting care-related processes, thus supporting credibility from the perspective of the end-users. RESULTS: The seven identified domain areas were person-centred nutritional care (the overarching theme); availability of food and drink; tools, resources and environment; relationship to others when eating and drinking; participation in activities; consistency of care and provision of information. CONCLUSIONS: This collaboratively developed, person-centred model can support the design of new education and training tools and be readily translated into existing programmes. Further research is needed to evaluate whether these evidence-informed approaches have been implemented successfully and adopted into practice and policy contexts and can demonstrate effectiveness for people living with dementia

    Delayed and Accelerated Aging Share Common Longevity Assurance Mechanisms

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    Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice. Subsequent analysis of significantly over-represented biological processes revealed suppression of the endocrine and energy pathways with increased stress responses in both delayed and premature aging. To test the relevance of these processes in natural aging, we compared the transcriptomes of liver, lung, kidney, and spleen over the entire murine adult lifespan and subsequently confirmed these findings on an independent aging cohort. The majority of genes showed similar expression changes in all four organs, indicating a systemic transcriptional response with aging. This systemic response included the same biological processes that are triggered in progeroid and long-lived mice. However, on a genome-wide scale, transcriptomes of naturally aged mice showed a strong association to progeroid but not to long-lived mice. Thus, endocrine and metabolic changes are indicative of “survival” responses to genotoxic stress or starvation, whereas genome-wide associations in gene expression with natural aging are indicative of biological age, which may thus delineate pro- and anti-aging effects of treatments aimed at health-span extension

    Sexually dimorphic gene expression in the heart of mice and men

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    The prevalence and clinical manifestation of several cardiovascular diseases vary considerably with sex and age. Thus, a better understanding of the molecular basis of these differences may represent a starting point for an improved gender-specific medicine. Despite the fact that sex-specific differences have been observed in the cardiovascular system of humans and animal models, systematic analyses of sexual dimorphisms at the transcriptional level in the healthy heart are missing. Therefore we performed gene expression profiling on mouse and human cardiac samples of both sexes and young as well as aged individuals and verified our results for a subset of genes using real-time polymerase chain reaction in independent left ventricular samples. To tackle the question whether sex differences are evolutionarily conserved, we also compared sexually dimorphic genes between both species. We found that genes located on sex chromosomes were the most abundant ones among the sexually dimorphic genes. Male-specific expression of Y-linked genes was observed in mouse hearts as well as in the human myocardium (e.g. Ddx3y, Eif2s3y and Jarid1d). Higher expression levels of X-linked genes were detected in female mice for Xist, Timp1 and Car5b and XIST, EIF2S3X and GPM6B in women. Furthermore, genes on autosomal chromosomes encoding cytochromes of the monoxygenase family (e.g. Cyp2b10), carbonic anhydrases (e.g. Car2 and Car3) and natriuretic peptides (e.g. Nppb) were identified with sex- and/or age-specific expression levels. This study underlines the relevance of sex and age as modifiers of cardiac gene expression

    AIDS and Other Manifestations of HIV Infection

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    Theta antigen and immunoglobulin on a tissue-cultured mouse lymphoma.

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    E1-4, a tissue culture established murine lymphoma, is shown to carry the θ-antigen and to have immunoglobulin in its membrane. Both are present in quantities similar to those found on normal C57 B1/6N thymocytes. This cell line may prove a useful model for the study of T cell membranes
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