Functional annotation signatures of disease susceptibility loci improve SNP association analysis.

BACKGROUND: Genetic association studies are conducted to discover genetic loci that contribute to an inherited trait, identify the variants behind these associations and ascertain their functional role in determining the phenotype. To date, functional annotations of the genetic variants have rarely played more than an indirect role in assessing evidence for association. Here, we demonstrate how these data can be systematically integrated into an association study's analysis plan. RESULTS: We developed a Bayesian statistical model for the prior probability of phenotype-genotype association that incorporates data from past association studies and publicly available functional annotation data regarding the susceptibility variants under study. The model takes the form of a binary regression of association status on a set of annotation variables whose coefficients were estimated through an analysis of associated SNPs in the GWAS Catalog (GC). The functional predictors examined included measures that have been demonstrated to correlate with the association status of SNPs in the GC and some whose utility in this regard is speculative: summaries of the UCSC Human Genome Browser ENCODE super-track data, dbSNP function class, sequence conservation summaries, proximity to genomic variants in the Database of Genomic Variants and known regulatory elements in the Open Regulatory Annotation database, PolyPhen-2 probabilities and RegulomeDB categories. Because we expected that only a fraction of the annotations would contribute to predicting association, we employed a penalized likelihood method to reduce the impact of non-informative predictors and evaluated the model's ability to predict GC SNPs not used to construct the model. We show that the functional data alone are predictive of a SNP's presence in the GC. Further, using data from a genome-wide study of ovarian cancer, we demonstrate that their use as prior data when testing for association is practical at the genome-wide scale and improves power to detect associations. CONCLUSIONS: We show how diverse functional annotations can be efficiently combined to create 'functional signatures' that predict the a priori odds of a variant's association to a trait and how these signatures can be integrated into a standard genome-wide-scale association analysis, resulting in improved power to detect truly associated variants

Transmission fiber chromatic dispersion dependence on temperature: implications on 40 Gb/s performance

In this letter we will evaluate the performance degradation of a 40 km high-speed (40 Gb/s) optical System, induced by optical fiber variations of the chromatic dispersion induced by temperature changes. The chromatic dispersion temperature sensitivity will be estimated based on the signal quality parameters

Analysis of antenal sensilla patterns of Rhodnius prolixus from Colombia and Venezuela

Antennal sensilla patterns were used to analyze population variation of domestic Rhodnius prolixus from six departments and states representing three biogeographical regions of Colombia and Venezuela. Discriminant analysis of the patterns of mechanoreceptors and of three types of chemoreceptors on the pedicel and flagellar segments showed clear differentiation between R. prolixus populations east and west of the Andean Cordillera. The distribution of thick and thin-walled trichoids on the second flagellar segment also showed correlation with latitude, but this was not seen in the patterns of other sensilla. The results of the sensilla patterns appear to be reflecting biogeographic features or population isolation rather than characters associated with different habitats and lend support to the idea that domestic R. prolixus originated in the eastern region of the Andes.Fil: Esteban, Lyda. Universidad Industrial de Santander; ColombiaFil: Angulo, Víctor Manuel. Universidad Industrial de Santander; ColombiaFil: Dora Feliciangeli, M.. Universidad de Carabobo; VenezuelaFil: Catala, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; Argentin

TGF β1 and PDGF AA override Collagen type I inhibition of proliferation in human liver connective tissue cells

BACKGROUND: A marked expansion of the connective tissue population and an abnormal deposition of extracellular matrix proteins are hallmarks of chronic and acute injuries to liver tissue. Liver connective tissue cells, also called stellate cells, derived from fibrotic liver have been thoroughly characterized and correspond phenotypically to myofibroblasts. They are thought to derive from fat-storing Ito cells in the perisinusoidal space and acquire a contractile phenotype when activated by tissue injury. In the last few years it has become evident that several peptide growth factors such as PDGF AA and TGF-β are involved in the development of fibrosis by modulating myofibroblast proliferation and collagen secretion. The fact that during the development of chronic fibrosis there is concomitant deposition of collagen, a known inhibitory factor, and sustained cell proliferation, raises the possibility that stellate cells from chronic liver fibrosis patients fail to respond to normal physiologic controls. METHODS: In this study we address whether cells from fibrotic liver patients respond to normal controls of proliferation. We compared cell proliferation of primary human liver connective tissue cells (LCTC) from patients with liver fibrosis and skin fibroblasts (SF) in the presence of collagens type I and IV; TGF-β, PDGF AA and combinations of collagen type I and TGF-β or PDGF AA. RESULTS: Our results indicate that despite displaying normal contact and collagen-induced inhibition of proliferation LCTC respond more vigorously to lower concentrations of PDGF AA. In addition, we show that collagen type I synergizes with growth factors to promote mitogenesis of LCTC but not SF. CONCLUSIONS: The synergistic interaction of growth factors and extracellular matrix proteins may underlie the development of chronic liver fibrosis

Effect of radiotherapy on freedom from seizures in dogs with brain tumors.

BACKGROUND: Seizures are a common presenting sign in dogs with brain tumors. HYPOTHESIS/OBJECTIVES: To investigate the effect of radiotherapy on freedom from brain tumor-associated seizures and survival time in dogs. ANIMALS: Thirty-two client-owned dogs with brain tumor-associated seizures; 18 received medical treatment and radiotherapy, 14 received medical treatment alone. METHODS: Multicenter retrospective study. Baseline characteristics (seizure semiology, magnetic resonance imaging [MRI] characteristics, and treatment) and duration of seizure freedom were recorded for the 2 treatment groups. Duration of seizure freedom between groups was compared (log-rank test) using Cox's proportional hazard analysis, with baseline characteristics entered as covariates. RESULTS: The duration of seizure freedom and survival time were significantly longer in the radiotherapy group (P < .001), with a mean of 24 months (95% confidence interval [CI], 14.3-33.8) versus 1.7 months in the control group (95% CI, 0.5-2.9) and a mean of 34.6 months (95% CI: 25.2-44.1) versus 6.2 months in the control group (95% CI, 2.6-9.7) respectively. Baseline characteristics were not associated with duration of seizure freedom after the start of treatment. In the radiotherapy group, 5 dogs were euthanized during the study period because of causes other than seizures. In the control group, recurrence of seizures was observed before death in all dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: A longer period of seizure freedom and longer survival time was observed in dogs with brain tumors after radiotherapy compared to medical treatment only. The pathophysiological mechanisms of epileptogenesis and the effect of radiation therapy on seizure control are unclear to date. Further prospective studies are needed

Global trends in ultraprocessed food and drink product sales and their association with adult body mass index trajectories

This study evaluated global trends in ultraprocessed food and drink (UPFD) volume sales/capita and associations with adult body mass index (BMI) trajectories. Total food/drink volume sales/capita from Euromonitor for 80 countries (2002‐2016) were matched to mean adult BMI from the NCD Risk Factor Collaboration (2002‐2014). Products were classified as UPFD/non‐UPFD according to the NOVA classification system. Mixed models for repeated measures were used to analyse associations between UPFD volume sales/capita and adult BMI trajectories, controlling for confounding factors. The increase in UPF volume sales was highest for South and Southeast Asia (67.3%) and North Africa and the Middle East (57.6%), while for UPD, the increase was highest for South and Southeast Asia (120.0%) and Africa (70.7%). In 2016, baked goods were the biggest contributor to UPF volume sales (13.1%‐44.5%), while carbonated drinks were the biggest contributor to UPD volume sales (40.2%‐86.0%). For every standard deviation increase (51 kg/capita, 2002) in UPD volume sales, mean BMI increased by 0.195 kg/m2 for men (P < .001) and 0.072 kg/m2 for women (P = .003). For every standard deviation (40 kg/capita, 2002) increase in UPF volume sales, mean BMI increased by 0.316 kg/m2 for men (P < .001), while the association was not significant for women. Increases in UPFD volume sales/capita were positively associated with population‐level BMI trajectories

RNA interference in Lepidoptera: an overview of successful and unsuccessful studies and implications for experimental design

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Predicting the detectability of oscillations in solar-type stars observed by Kepler

Asteroseismology of solar-type stars has an important part to play in the exoplanet program of the NASA Kepler Mission. Precise and accurate inferences on the stellar properties that are made possible by the seismic data allow very tight constraints to be placed on the exoplanetary systems. Here, we outline how to make an estimate of the detectability of solar-like oscillations in any given Kepler target, using rough estimates of the temperature and radius, and the Kepler apparent magnitude.Comment: 21 pages, 6 figures, accepted for publication Astrophysical Journa

Medical management of spinal epidural empyema in five dogs

CASE DESCRIPTION 5 dogs were examined because of clinical signs of myelopathy, including signs of pain associated with the spinal region and rapidly progressive neurologic deficits. CLINICAL FINDINGS In all dogs, results of MRI were consistent with spinal epidural empyema. Concurrent infectious processes were identified at adjacent or distant sites in all dogs, including diskospondylitis, prostatitis, dermatitis, paraspinal infection following a penetrating injury, urinary tract infection, and pyothorax. Bacteria were isolated from 3 dogs; Escherichia coli was isolated from blood, urine, and prostatic wash samples from 1 dog; a Pasteurella sp was isolated from a percutaneous aspirate from an adjacent infected wound in a second dog; and a Corynebacterium sp was isolated from a thoracic fluid sample from a third dog. For the remaining 2 dogs, results of bacterial culture were negative. TREATMENT AND OUTCOME All dogs showed clinical improvement within 2 weeks after initiation of antimicrobial treatment, and all had an excellent long-term outcome. CLINICAL RELEVANCE In dogs, spinal epidural empyema has previously been regarded as a surgical emergency. Findings for dogs in the present report suggested that, as is the case for humans, selected dogs with spinal epidural empyema may be successfully managed with medical treatment alone

Seasonal Depletion of the Dissolved Iron Reservoirs in the Sub-Antarctic zone of the Southern Atlantic Ocean

Seasonal progression of dissolved iron (DFe) concentrations in the upper water column were examined during four occupations in the Atlantic sector of the Southern Ocean. DFe inventories from euphotic and aphotic reservoirs decreased progressively from July to February, while dissolved inorganic nitrogen (DIN) decreased from July to January with no significant change between January and February. Results suggest that between July and January, DFe loss from both euphotic and aphotic reservoirs were predominantly in support of phytoplankton growth (Iron to carbon (Fe:C) uptake ratio of 16±3 μmol mol‐1) highlighting the importance of the “winter DFe‐reservoir” for biological uptake. During January to February, excess loss of DFe relative to DIN (Fe:C uptake ratio of 44±8 μmol mol‐1 and aphotic DFe loss rate of 0.34±0.06 μmol m‐2 d‐1) suggests that scavenging is the dominant removal mechanism of DFe from the aphotic, while continued production is likely supported by recycled nutrients. Plain Language Summary Trace metal iron is one of the limiting nutrients for primary productivity in the Southern Ocean; however the relative importance of seasonal iron supply and sinks remains poorly understood, due to sparse data coverage across the seasonal cycle and lack of high‐resolution dissolved iron (DFe) measurements. Here, we present four “snap‐shots” of DFe measurements at a single station in the south‐east Southern Atlantic Ocean (one in winter and three in late spring‐summer), to address the seasonal evolution of DFe and dissolved inorganic nitrogen (DIN) concentrations within the biologically active sunlit and subsurface reservoirs. We observed a seasonal depletion of DFe inventories from July‐February, while DIN inventories decreases from July‐January with no concomitant changes between January‐February. This suggests that, in addition to biological uptake in the sunlit layer, the observed decrease in DFe inventories below this (relative to DIN) is driven by aggregation and incorporation of iron particles into larger "marine snow" sinking particles, while nutrient recycling is driving the observed continuation of primary productivity during late summer. Our results provide insight into seasonal change of DFe availability in different reservoirs where interplay between removal and supply processes are controlling its distributions and bioavailability to support upper surface primary production