173 research outputs found

    Iceberg topography and volume classification using TanDEM-X interferometry

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    Icebergs in polar regions affect water salinity, alter marine habitats, and impose serious hazards on maritime operations and navigation. These impacts mainly depend on the iceberg volume, which remains an elusive parameter to measure. We investigate the capability of TanDEM-X bistatic single-pass synthetic aperture radar interferometry (InSAR) to derive iceberg subaerial morphology and infer total volume. We cross-verify InSAR results with Operation IceBridge (OIB) data acquired near Wordie Bay, Antarctica, as part of the OIB/TanDEM-X Antarctic Science Campaign (OTASC). While icebergs are typically classified according to size based on length or maximum height, we develop a new volumetric classification approach for applications where iceberg volume is relevant. For icebergs with heights exceeding 5 m, we find iceberg volumes derived from TanDEM-X and OIB data match within 7 %. We also derive a range of possible iceberg keel depths relevant to grounding and potential impacts on subsea installations. These results suggest that TanDEM-X could pave the way for future single-pass interferometric systems for scientific and operational iceberg mapping and classification based on iceberg volume and keel depth

    Comparative Analysis of Measures of Viral Reservoirs in HIV-1 Eradication Studies

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    HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy (HAART). The best characterized reservoir is a small, difficult-to-quantify pool of resting memory CD4+ T cells carrying latent but replication-competent viral genomes. Because strategies targeting this latent reservoir are now being tested in clinical trials, well-validated high-throughput assays that quantify this reservoir are urgently needed. Here we compare eleven different approaches for quantitating persistent HIV-1 in 30 patients on HAART, using the original viral outgrowth assay for resting CD4+ T cells carrying inducible, replication-competent viral genomes as a standard for comparison. PCR-based assays for cells containing HIV-1 DNA gave infected cell frequencies at least 2 logs higher than the viral outgrowth assay, even in subjects who started HAART during acute/early infection. This difference may reflect defective viral genomes. The ratio of infected cell frequencies determined by viral outgrowth and PCR-based assays varied dramatically between patients. Although strong correlations with the viral outgrowth assay could not be formally excluded for most assays, correlations achieved statistical significance only for integrated HIV-1 DNA in peripheral blood mononuclear cells and HIV-1 RNA/DNA ratio in rectal CD4+ T cells. Residual viremia was below the limit of detection in many subjects and did not correlate with the viral outgrowth assays. The dramatic differences in infected cell frequencies and the lack of a precise correlation between culture and PCR-based assays raise the possibility that the successful clearance of latently infected cells may be masked by a larger and variable pool of cells with defective proviruses. These defective proviruses are detected by PCR but may not be affected by reactivation strategies and may not require eradication to accomplish an effective cure. A molecular understanding of the discrepancy between infected cell frequencies measured by viral outgrowth versus PCR assays is an urgent priority in HIV-1 cure research

    Home visits by neighborhood Mentor Mothers provide timely recovery from childhood malnutrition in South Africa: results from a randomized controlled trial

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    Abstract Background Child and infant malnourishment is a significant and growing problem in the developing world. Malnourished children are at high risk for negative health outcomes over their lifespans. Philani, a paraprofessional home visiting program, was developed to improve childhood nourishment. The objective of this study is to evaluate whether the Philani program can rehabilitate malnourished children in a timely manner. Methods Mentor Mothers were trained to conduct home visits. Mentor Mothers went from house to house in assigned neighborhoods, weighed children age 5 and younger, and recruited mother-child dyads where there was an underweight child. Participating dyads were assigned in a 2:1 random sequence to the Philani intervention condition (n = 536) or a control condition (n = 252). Mentor Mothers visited dyads in the intervention condition for one year, supporting mothers' problem-solving around nutrition. All children were weighed by Mentor Mothers at baseline and three, six, nine and twelve month follow-ups. Results By three months, children in the intervention condition were five times more likely to rehabilitate (reach a healthy weight for their ages) than children in the control condition. Throughout the course of the study, 43% (n = 233 of 536) of children in the intervention condition were rehabilitated while 31% (n = 78 of 252) of children in the control condition were rehabilitated. Conclusions Paraprofessional Mentor Mothers are an effective strategy for delivering home visiting programs by providing the knowledge and support necessary to change the behavior of families at risk

    Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases

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    Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance. Methods: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins. Results: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F). Conclusion: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases

    Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases

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    BACKGROUND: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance.METHODS: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins.RESULTS: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F).CONCLUSION: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases.</p

    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

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    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

    The biogeography of community assembly: latitude and predation drive variation in community trait distribution in a guild of epifaunal crustaceans

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    While considerable evidence exists of biogeographic patterns in the intensity of species interactions, the influence of these patterns on variation in community structure is less clear. Studying how the distributions of traits in communities vary along global gradients can inform how variation in interactions and other factors contribute to the process of community assembly. Using a model selection approach on measures of trait dispersion in crustaceans associated with eelgrass (Zostera marina) spanning 30 degrees of latitude in two oceans, we found that dispersion strongly increased with increasing predation and decreasing latitude. Ocean and epiphyte load appeared as secondary predictors; Pacific communities were more overdispersed while Atlantic communities were more clustered, and increasing epiphytes were associated with increased clustering. By examining how species interactions and environmental filters influence community structure across biogeographic regions, we demonstrate how both latitudinal variation in species interactions and historical contingency shape these responses. Community trait distributions have implications for ecosystem stability and functioning, and integrating large-scale observations of environmental filters, species interactions and traits can help us predict how communities may respond to environmental change.info:eu-repo/semantics/publishedVersio

    A Pleistocene legacy structures variation in modern seagrass ecosystems

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    Distribution of Earth's biomes is structured by the match between climate and plant traits, which in turn shape associated communities and ecosystem processes and services. However, that climate-trait match can be disrupted by historical events, with lasting ecosystem impacts. As Earth's environment changes faster than at any time in human history, critical questions are whether and how organismal traits and ecosystems can adjust to altered conditions. We quantified the relative importance of current environmental forcing versus evolutionary history in shaping the growth form (stature and biomass) and associated community of eelgrass (Zostera marina), a widespread foundation plant of marine ecosystems along Northern Hemisphere coastlines, which experienced major shifts in distribution and genetic composition during the Pleistocene. We found that eelgrass stature and biomass retain a legacy of the Pleistocene colonization of the Atlantic from the ancestral Pacific range and of more recent within-basin bottlenecks and genetic differentiation. This evolutionary legacy in turn influences the biomass of associated algae and invertebrates that fuel coastal food webs, with effects comparable to or stronger than effects of current environmental forcing. Such historical lags in phenotypic acclimatization may constrain ecosystem adjustments to rapid anthropogenic climate change, thus altering predictions about the future functioning of ecosystems.This work was supported by the US NSF (OCE-1031061, OCE-1336206, OCE0-1336741, OCE-1336905) and the Smithsonian Institution. F.T. was supported by José Castillejo Award CAS14/00177. A.H.E. was supported by the FCT (Foundation for Science and Technology) through Project UIDB/04326/2020 and Contract CEECINST/00114/2018. This is Contribution 106 from the Smithsonian’s MarineGEO and Tennenbaum Marine Observatories Network and Contribution 4105 of the Virginia Institute of Marine Science, College of William & Mary

    Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study

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    Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio <1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studie
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