502 research outputs found

    Towards a general framework for predicting threat status of data-deficient species from phylogenetic, spatial and environmental information

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    In taxon-wide assessments of threat status many species remain not included owing to lack of data. Here, we present a novel spatial-phylogenetic statistical framework that uses a small set of readily available or derivable characteristics, including phylogenetically imputed body mass and remotely sensed human encroachment, to provide initial baseline predictions of threat status for data-deficient species. Applied to assessed mammal species worldwide, the approach effectively identifies threatened species and predicts the geographical variation in threat. For the 483 data-deficient species, the models predict highly elevated threat, with 69% ‘at-risk’ species in this set, compared with 22% among assessed species. This results in 331 additional potentially threatened mammals, with elevated conservation importance in rodents, bats and shrews, and countries like Colombia, Sulawesi and the Philippines. These findings demonstrate the future potential for combining phylogenies and remotely sensed data with species distributions to identify species and regions of conservation concern

    The CTGF -945GC polymorphism is not associated with plasma CTGF and does not predict nephropathy or outcome in type 1 diabetes

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    The -945GC polymorphism (rs6918698) in the connective tissue growth factor gene promoter (CTGF/CCN-2) has been associated with end organ damage in systemic sclerosis. Because CTGF is important in progression of diabetic kidney disease, we investigated whether the -945GC polymorphism is associated with plasma CTGF level and outcome in type 1 diabetes

    Resequencing of genes for transforming growth factor β1 (TGFB1) type 1 and 2 receptors (TGFBR1, TGFBR2), and association analysis of variants with diabetic nephropathy

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    BACKGROUND: Diabetic nephropathy is the leading cause of end stage renal failure in the western world. There is substantial epidemiological evidence supporting a genetic predisposition to diabetic nephropathy, however the exact molecular mechanisms remain unknown. Transforming growth factor (TGFβ1) is a crucial mediator in the pathogenesis of diabetic nephropathy. METHODS: We investigated the role of five known single nucleotide polymorphisms (SNPs) in the TGFB1 gene for their association with diabetic nephropathy in an Irish, type 1 diabetic case (n = 272) control (n = 367) collection. The activity of TGFβ1 is facilitated by the action of type 1 and type 2 receptors, with both receptor genes (TGFBR1 and TGFBR2) shown to be upregulated in diabetic kidney disease. We therefore screened TGFBR1 and TGFBR2 genes for genomic variants using WAVE™ (dHPLC) technology and confirmed variants by direct capillary sequencing. Allele frequencies were determined in forty-eight healthy individuals. Data for all SNPs was assessed for Hardy Weinberg equilibrium, with genotypes and allele frequencies compared using the χ(2 )test for contingency tables. Patterns of linkage disequilibrium were established and common haplotypes estimated. RESULTS: Fifteen variants were identified in these genes, seven of which are novel, and putatively functional SNPs were subsequently genotyped using TaqMan™, Invader™ or Pyrosequencing(® )technology. No significant differences (p > 0.1) were found in genotype or allele distributions between cases and controls for any of the SNPs assessed. CONCLUSION: Our results suggest common variants in TGFB1, TGFBR1 and TGFBR2 genes do not strongly influence genetic susceptibility to diabetic nephropathy in an Irish Caucasian population

    Origin and Epidemiological History of HIV-1 CRF14_BG

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    This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Users must also make clear the license terms under which the work was published. CC BY Licence: http://creativecommons.org/licenses/by/4.0/Background: CRF14_BG isolates, originally found in Spain, are characterized by CXCR4 tropism and rapid disease progression. This study aimed to identify the origin of CRF14_BG and reconstruct its epidemiological history based on new isolates from Portugal.Methodology/Principal Findings: C2V3C3 env gene sequences were obtained from 62 samples collected in 1993–1998 from Portuguese HIV-1 patients. Full-length genomic sequences were obtained from three patients. Viral subtypes, diversity, divergence rate and positive selection were investigated by phylogenetic analysis. The molecular structure of the genomes was determined by bootscanning. A relaxed molecular clock model was used to date the origin of CRF14_BG. Geno2pheno was used to predict viral tropism. Subtype B was the most prevalent subtype (45 sequences; 73%) followed by CRF14_BG (8; 13%), G (4; 6%), F1 (2; 3%), C (2; 3%) and CRF02_AG (1; 2%). Three CRF14_BG sequences were derived from 1993 samples. Near full-length genomic sequences were strongly related to the CRF14_BG isolates from Spain. Genetic diversity of the Portuguese isolates was significantly higher than the Spanish isolates (0.044 vs 0.014, P,0.0001). The mean date of origin of the CRF14_BG cluster was estimated to be 1992 (range, 1989 and 1996) based on the subtype G genomic region and 1989 (range, 1984–1993) based on the subtype B genomic region. Most CRF14_BG strains (78.9%) were predicted to be CXCR4. Finally, up to five amino acids were under selective pressure in subtype B V3 loop whereas only one was found in the CRF14_BG cluster.Conclusions: CRF14_BG emerged in Portugal in the early 1990 s soon after the beginning of the HIV-1 epidemics, spread to Spain in late 1990 s as a consequence of IVDUs migration and then to the rest of Europe. CXCR4 tropism is a general characteristic of this CRF that may have been selected for by escape from neutralizing antibody response

    Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection

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    T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately. In SARS-COV-2 PCR+ individuals, a wave of TCRs strongly but transiently expand, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains but not with circulating human coronaviruses. Many expanding CDR3s were present at high frequency in pre-pandemic repertoires. Early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the preinfection naive repertoire. High-frequency naive precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection

    Detroit's East Side Village Health Worker Partnership: Community-Based Lay Health Advisor Intervention in an Urban Area

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    In recent years, there have been few reports in the literature of interventions using a lay health advisor approach in an urban area. Consequently, little is known about how implementation of this type of community health worker model, which has been used extensively in rural areas, may differ in an urban area. This article describes the implementation of the East Side Village Health Worker Partnership, a lay health advisor intervention, in Detroit, Michigan, and notes how participatory action research methods and principles for community-based partnership research are being used to guide the intervention. Findings are presented on how the urban context is affecting the design and implementation of this intervention. Implications of the findings for health educators are also presented and include the utility of a participatory action research approach, the importance of considering the context and history of a community in designing a health education intervention, and the importance of recognizing and considering the differences between rural and urban settings when designing a health education intervention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67390/2/10.1177_109019819802500104.pd
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