20 research outputs found
Metabolic Effects of Cyclic Parenteral Nutrition Infusion in Adults and Children
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141574/1/ncp0277.pd
The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts
Biodiversity continues to decline in the face of increasing anthropogenic pressures
such as habitat destruction, exploitation, pollution and introduction of
alien species. Existing global databases of species’ threat status or population
time series are dominated by charismatic species. The collation of datasets with
broad taxonomic and biogeographic extents, and that support computation of
a range of biodiversity indicators, is necessary to enable better understanding of
historical declines and to project – and avert – future declines. We describe and
assess a new database of more than 1.6 million samples from 78 countries representing
over 28,000 species, collated from existing spatial comparisons of
local-scale biodiversity exposed to different intensities and types of anthropogenic
pressures, from terrestrial sites around the world. The database contains
measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35)
biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains
more than 1% of the total number of all species described, and more than
1% of the described species within many taxonomic groups – including flowering
plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans
and hymenopterans. The dataset, which is still being added to, is
therefore already considerably larger and more representative than those used
by previous quantitative models of biodiversity trends and responses. The database
is being assembled as part of the PREDICTS project (Projecting Responses
of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk).
We make site-level summary data available alongside this article. The full database
will be publicly available in 2015
Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study
Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation
Social Networks and Civic Participation and Efficacy in Two Evangelical Protestant Churches
This research note examines the proposition that participation in church—particularly the social interaction that accompanies church participation—is an important source of social capital that promotes civic activity and efficacy. Employing survey data from over 600 attendees of two evangelical Protestant churches, we tested hypotheses linking churchgoers’ social networks to their levels of civic efficacy and participation. Three key findings emerged. First, the number of friends in church was positively associated with churchgoers’ civic efficacy, religious civic activity, and secular civic activity, while the number of friends outside of church was unrelated to these outcomes. Second, the association between in-church networks and secular civic activity was partially mediated by civic efficacy. Third, church attendance moderated the association between in-church friends and secular civic activities such that high attending churchgoers with few in-church friends were far less likely to participate in secular civic activities. Taken together, these findings illustrate the importance of in-church social networks for Evangelical Protestants’ civic participation and feelings of civic efficacy, in contrast to out of church social networks which had little overall impact on these factors
'When Leaderless is Meaningless (and When it Matters Most): An Organizational Typology of Leadership Decapitation and its Effectiveness'
MSH3 modifies somatic instability and disease severity in Huntington’s and myotonic dystrophy type 1
Huntington’s disease and myotonic dystrophy type 1. A recent Huntington’s disease genome-wide association study found
rs557874766, an imputed single nucleotide polymorphism located within a polymorphic 9 bp tandem repeat in MSH3/DHFR,
as the variant most significantly associated with progression in Huntington’s disease. Using Illumina sequencing in Huntington’s
disease and myotonic dystrophy type 1 subjects, we show that rs557874766 is an alignment artefact, the minor allele for which
corresponds to a three-repeat allele in MSH3 exon 1 that is associated with a reduced rate of somatic CAG CTG expansion
(P = 0.004) and delayed disease onset (P = 0.003) in both Huntington’s disease and myotonic dystrophy type 1, and slower
progression (P = 3.86 10 7) in Huntington’s disease. RNA-Seq of whole blood in the Huntington’s disease subjects found
that repeat variants are associated with MSH3 and DHFR expression. A transcriptome-wide association study in the
Huntington’s disease cohort found increased MSH3 and DHFR expression are associated with disease progression. These results
suggest that variation in the MSH3 exon 1 repeat region influences somatic expansion and disease phenotype in Huntington’s
disease and myotonic dystrophy type 1, and suggests a common DNA repair mechanism operates in both repeat expansion
diseases.UK DementiaResearch Institute/[]//Reino UnidoMedical Research Council/[MR/L010305/1]/MRC/Reino UnidoEuropean Union’s Seventh Framework Programme/[2012-305121]/FP7 2007-2013/Unión EuropeaRosetrees Trust/[JS16/M574]//Reino UnidoUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA