283 research outputs found

    Seasonal Habitat Selection by American White Pelicans

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    Resource utilization strategies of avian migrants are a major concern for conservation and management. Understanding seasonal habitat selection by migratory birds helps us explain the ongoing continental declines of migratory bird populations. Our objective was to compare the secondorder and third-order habitat selection by the American White Pelican (Pelecanus erythrorhynchos; hereafter pelican) between the breeding and non-breeding grounds. We tested the Lack hypothesis that habitat selection by migratory birds is stronger on the breeding grounds than on the nonbreeding grounds. We used random-effect Dirichlet-multinomial models to estimate the second-order habitat selection between the seasons with the GPS locations of 32 tracked pelicans. We used Gaussian Markov random field models to estimate the third-order habitat selection by pelicans at the breeding and non-breeding grounds, accounting for spatial autocorrelation. Pelicans strongly selected waterbodies and wetlands at both non-breeding and breeding grounds, tracking their foraging habitats between the seasons at the home range level. However, pelicans exhibited seasonal differences in the strength of the third-order selection of wetlands and waterbodies with foraging habitat selection being stronger at the breeding grounds than at the non-breeding grounds, supporting the Lack hypothesis

    Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway

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    Cell signaling events elicit changes in mitochondrial shape and activity. However, few mitochondrial proteins that interact with signaling pathways have been identified. Candidates include the conserved mitochondrial Rho (Miro) family of proteins, which contain two GTPase domains flanking a pair of calcium-binding EF-hand motifs. We show that Gem1p (yeast Miro; encoded by YAL048C) is a tail-anchored outer mitochondrial membrane protein. Cells lacking Gem1p contain collapsed, globular, or grape-like mitochondria. We demonstrate that Gem1p is not an essential component of characterized pathways that regulate mitochondrial dynamics. Genetic studies indicate both GTPase domains and EF-hand motifs, which are exposed to the cytoplasm, are required for Gem1p function. Although overexpression of a mutant human Miro protein caused increased apoptotic activity in cultured cells (Fransson et al., 2003. J. Biol. Chem. 278:6495–6502), Gem1p is not required for pheromone-induced yeast cell death. Thus, Gem1p defines a novel mitochondrial morphology pathway which may integrate cell signaling events with mitochondrial dynamics

    Antigenic Characterization of H3 Subtypes of Avian Influenza A Viruses from North America

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    Besides humans, H3 subtypes of influenza A viruses (IAVs) can infect various animal hosts, including avian, swine, equine, canine, and sea mammal species. These H3 viruses are both antigenically and genetically diverse. Here, we characterized the antigenic diversity of contemporary H3 avian IAVs recovered from migratory birds in North America. Hemagglutination inhibition (HI) assays were performed on 37 H3 isolates of avian IAVs recovered from 2007 to 2011 using generated reference chicken sera. These isolates were recovered from samples taken in the Atlantic, Mississippi, Central, and Pacific waterfowl migration flyways. Antisera to all the tested H3 isolates cross-reacted with each other and, to a lesser extent, with those to H3 canine and H3 equine IAVs. Antigenic cartography showed that the largest antigenic distance among the 37 avian IAVs is about four units, and each unit corresponds to a 2 log 2 difference in the HI titer. However, none of the tested H3 IAVs cross-reacted with ferret sera derived from contemporary swine and human IAVs. Our results showed that the H3 avian IAVs we tested lacked significant antigenic diversity, and these viruses were antigenically different from those circulating in swine and human populations. This suggests that H3 avian IAVs in North American waterfowl are antigenically relatively stable. Además de infectar a los seres humanos, los subtipos H3 del virus de la influenza A (IAVs) pueden infectar a varios huéspedes animales, incluyendo aves, porcinos, equinos, caninos, y especies de mamíferos marinos. Estos virus H3 son tanto antigénica y genéticamente diversos. En este estudio, se caracterizó la diversidad antigénica de virus H3 contemporáneos recuperados de aves migratorias en América del Norte. Se realizaron pruebas de inhibición de la hemaglutinación (HI) en 37 H3 aislamientos de origen aviar recuperados de 2007 a 2011 usando sueros de pollo de referencia. Estos aislamientos fueron recuperados de las muestras tomadas de las rutas migratorias de aves acuáticas del Atlántico, Mississippi, Centro y del Pacífico. Los antisueros de todos los aislamientos H3 analizados mostraron reacciones cruzadas entre sí y en menor medida, con aquellos virus H3 de origen canino y equino. La cartografía antigénica demostró que la mayor distancia antigénica entre los 37 virus de este tipo de aves es de aproximadamente cuatro unidades, y cada unidad corresponde a una diferencia de dos logaritmos en el título de inhibición de la hemaglutinación. Sin embargo, ninguno de los virus H3 de este tipo mostró reacción cruzada con sueros de hurón específicos para virus de cerdos y humanos contemporáneos. Estos resultados mostraron que los virus H3 de origen aviar que se analizaron carecían de diversidad antigénica significativa y estos virus fueron antigénicamente diferentes de las que circulan en poblaciones de cerdos y de humanos. Esto sugiere que los virus H3 de aves acuáticas de América del Norte son relativamente estables antigénicamente

    Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: Potential therapy for postoperative pulmonary hypertension

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    ObjectivePulmonary hypertension may complicate surgical correction of congenital heart defects, resulting in increased morbidity and mortality. We have previously shown that plasma levels of the nitric oxide precursors citrulline and arginine drop precipitously after congenital cardiac surgery and that oral citrulline supplementation may be protective against the development of pulmonary hypertension. In this study, we assessed the safety and pharmacokinetic profile of intravenous citrulline as a potential therapy for postoperative pulmonary hypertension.MethodsThe initial phase of this investigation was a dose-escalation study of intravenously administered citrulline in infants and children undergoing one of five congenital cardiac surgical procedures (phase 1). The primary safety outcome was a 20% drop in mean arterial blood pressure from the baseline pressure recorded after admission to the intensive care unit. Based on our previous work, the target circulating plasma citrulline trough was 80 to 100 μmol/L. Each patient was given two separate doses of citrulline: the first in the operating room immediately after initiation of cardiopulmonary bypass and the second 4 hours later in the pediatric intensive care unit. Stepwise dose escalations included 50 mg/kg, 100 mg/kg, and 150 mg/kg. After model-dependent pharmacokinetic analysis, we enrolled an additional 9 patients (phase 2) in an optimized dosing protocol that replaced the postoperative dose with a continuous infusion of citrulline at 9 mg/(kg·h) for 48 hours postoperatively.ResultsThe initial stepwise escalation protocol (phase 1) revealed that an intravenous citrulline dose of 150 mg/kg given after initiation of cardiopulmonary bypass yielded a trough level of in the target range of approximately 80 to 100 μmol/L 4 hours later. The postoperative dose revealed that the clearance of intravenously administered citrulline was 0.6 L/(h·kg), with a volume of distribution of 0.9 L/kg and estimated half-life of 60 minutes. Because of the short half-life, we altered the protocol to replace the postoperative dose with a continuous infusion of 9 mg/(kg·h). An additional 9 patients were studied with this continuous infusion protocol (phase 2). Mean plasma citrulline levels were maintained at approximately 125 μmol/L, with a calculated clearance of 0.52 L/(h·kg). None of the 17 patients studied had a 20% drop in mean arterial blood pressure from baseline.ConclusionsIn this first report of the use of intravenous citrulline in humans, we found citrulline to be both safe and well tolerated in infants and young children undergoing congenital cardiac surgery. Because of the rapid clearance, the optimal dosing regimen was identified as an initial bolus of 150 mg/kg given at the initiation of cardiopulmonary bypass, followed 4 hours later by a postoperative infusion of 9 mg/(kg·h) continued up to 48 hours. Using this regimen, plasma arginine, citrulline, and nitric oxide metabolite levels were well maintained. Intravenous citrulline needs to be studied further as a potential therapy for postoperative pulmonary hypertension

    The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

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    Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines

    Scientific Objectives of Einstein Telescope

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    The advanced interferometer network will herald a new era in observational astronomy. There is a very strong science case to go beyond the advanced detector network and build detectors that operate in a frequency range from 1 Hz-10 kHz, with sensitivity a factor ten better in amplitude. Such detectors will be able to probe a range of topics in nuclear physics, astronomy, cosmology and fundamental physics, providing insights into many unsolved problems in these areas.Comment: 18 pages, 4 figures, Plenary talk given at Amaldi Meeting, July 201

    ‘Does My Haltung Look Big In This?”: The Use of Social Pedagogical Theory for the Development of Ethical and Value Led Practice

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    The aim of this article is to set out how the use of social pedagogical Haltung can support the exploration of values and how this informs and shapes a practitioner’s direct work. Haltung is a German concept that has no direct English translation but means ‘mind set’, ‘ethos’ or ‘attitude’ (Eichsteller, 2010) and relates to an individual’s value base. Mührel’s (2008, cited in Eichsteller, 2010), sets out that a social pedagogical Haltung is based on the two concepts of empathic understanding and regard. This paper argues that the use of a social pedagogical Haltung gives practitioners a philosophical framework to support the reflection of core values and ethics held on a personal level. It also supports an understanding of how these influence practitioners and students when using ‘self’ in relationship based practice. The understanding of Haltung is important but for social pedagogical practice to be undertaken it also has to be demonstrated by actions. The reflective activity Values Alive in Practice, set out in this article, provides a tool for social workers, practitioners and students to critically explore their own values and practice and make more meaningful connections between their Haltung and their behaviours demonstrated in their everyday work. In the UK, values and standards for social work practice are set out by British Association of Social Work and Social Work England. Arguably, these have, at times, been reduced to a checklist for students and practitioners and can lack more in depth and explicit links to practice. The analysis of practice is more likely to focus on the skills and abilities of practitioners rather than the value base that underpins these. Whilst the understanding and key application of core knowledge and skills is essential for competent social work practice (Forrester et al., 2019), this article argues that it must also be supported and shaped by ethical principles. This article seeks to explore how social workers can be supported to adopt value led approaches to complex work within an outcome focussed culture

    Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes

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    SummarySomatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk
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