359 research outputs found

    Rapid Evolution of BRCA1 and BRCA2 in Humans and Other Primates

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    The maintenance of chromosomal integrity is an essential task of every living organism and cellular repair mechanisms exist to guard against insults to DNA. Given the importance of this process, it is expected that DNA repair proteins would be evolutionarily conserved, exhibiting very minimal sequence change over time. However, BRCA1, an essential gene involved in DNA repair, has been reported to be evolving rapidly despite the fact that many protein-altering mutations within this gene convey a significantly elevated risk for breast and ovarian cancers. Results: To obtain a deeper understanding of the evolutionary trajectory of BRCA1, we analyzed complete BRCA1 gene sequences from 23 primate species. We show that specific amino acid sites have experienced repeated selection for amino acid replacement over primate evolution. This selection has been focused specifically on humans and our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). After examining BRCA1 polymorphisms in 7 bonobo, 44 chimpanzee, and 44 rhesus macaque (Macaca mulatta) individuals, we find considerable variation within each of these species and evidence for recent selection in chimpanzee populations. Finally, we also sequenced and analyzed BRCA2 from 24 primate species and find that this gene has also evolved under positive selection. Conclusions: While mutations leading to truncated forms of BRCA1 are clearly linked to cancer phenotypes in humans, there is also an underlying selective pressure in favor of amino acid-altering substitutions in this gene. A hypothesis where viruses are the drivers of this natural selection is discussed.National Institutes of Health R01-GM-093086, 8U42OD011197-13National Science Foundation BCS-07115972Burroughs Wellcome FundMolecular Bioscience

    Pre- and post-partum variation in wool cortisol and wool micron in Australian Merino ewe sheep (Ovis aries)

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    An individual merino sheep's output of wool production is influenced by synergistic interactions of sheep genetics, climate, farm management, and nutrition available to the whole flock. The price paid to the producer for this wool commodity is determined via numerous tested parameters and/or subjective appraisal of the raw greasy wool. This research investigated the level of variation in wool cortisol (a physiological stress biomarker) and wool micron (MIC) in Merino ewes (Ovis aries), pre-partum and post-lambing (lactation/lambs at foot), using maiden ewe (n = 38) managed in an outdoor paddock in a commercial farm. The key findings of this study are; (1) wool quality indicators showed a significant variation between pre- and post-parturition including significant reduction in MIC and (2) there was a negative correlation between wool cortisol levels and wool micron pre-parturition (rs = -0.179, p < 0.05). This relationship between wool cortisol and wool micron was positive (rs = +0.29, p < 0.05) during post-parturition suggesting that ewes with lambs at foot ended up with finer wool (reduction in fibre diameter) but they also maintained high levels of wool cortisol. Furthermore, the comfort factor, curvature, standard deviation and spin fineness of the wool were also significantly reduced post-parturition. The results of this study show that metabolic resources partitioning in ewe associated with pregnancy and lambing can result in a reduction in wool quality indices. The activity of the HPA-axis is attenuated during late gestation and parturition as a maternal adaptation; however, the results of our study show that wool cortisol remained similar between pre- and post-lambing. This result indicates that environmental stressors that may have been operating on farm (e.g., cold winter period) could influence on maternal physiological stress response however the exact level of influence of environment conditions on ewe stress levels and productivity traits (e.g., lambing success and wool quality) warrants further investigation. In conclusion, the use of top-knot wool sampling in combination with wool cortisol analysis provides researchers with a convenient method to quantify wool quality and physiological stress simultaneously under commercial sheep production

    Second-order rotational effects on the r-modes of neutron stars

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    Techniques are developed here for evaluating the r-modes of rotating neutron stars through second order in the angular velocity of the star. Second-order corrections to the frequencies and eigenfunctions for these modes are evaluated for neutron star models. The second-order eigenfunctions for these modes are determined here by solving an unusual inhomogeneous hyperbolic boundary-value problem. The numerical techniques developed to solve this unusual problem are somewhat non-standard and may well be of interest beyond the particular application here. The bulk-viscosity coupling to the r-modes, which appears first at second order, is evaluated. The bulk-viscosity timescales are found here to be longer than previous estimates for normal neutron stars, but shorter than previous estimates for strange stars. These new timescales do not substantially affect the current picture of the gravitational radiation driven instability of the r-modes either for neutron stars or for strange stars.Comment: 13 pages, 5 figures, revte

    What’s Next for Acute Heart Failure Research?

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    Each year over one million patients with acute heart failure (AHF) present to a United States emergency department (ED). The vast majority are hospitalized for further management. The length of stay and high postdischarge event rate in this cohort have changed little over the past decade. Therapeutic trials have failed to yield substantive improvement in postdischarge outcomes; subsequently, AHF care has changed little in the past 40 years. Prior research studies have been fragmented as either “inpatient” or “ED-based.” Recognizing the challenges in identification and enrollment of ED patients with AHF, and the lack of robust evidence to guide management, an AHF clinical trials network was developed. This network has demonstrated, through organized collaboration between cardiology and emergency medicine, that many of the hurdles in AHF research can be overcome. The development of a network that supports the collaboration of acute care and HF researchers, combined with the availability of federally funded infrastructure, will facilitate more efficient conduct of both explanatory and pragmatic trials in AHF. Yet many important questions remain, and in this document our group of emergency medicine and cardiology investigators have identified four high-priority research areas

    Corn Nitrogen Nutrition Index Prediction Improved by Integrating Genetic, Environmental, and Management Factors with Active Canopy Sensing Using Machine Learning

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    Accurate nitrogen (N) diagnosis early in the growing season across diverse soil, weather, and management conditions is challenging. Strategies using multi-source data are hypothesized to perform significantly better than approaches using crop sensing information alone. The objective of this study was to evaluate, across diverse environments, the potential for integrating genetic (e.g., comparative relative maturity and growing degree units to key developmental growth stages), environmental (e.g., soil and weather), and management (e.g., seeding rate, irrigation, previous crop, and preplant N rate) information with active canopy sensor data for improved corn N nutrition index (NNI) prediction using machine learning methods. Thirteen site-year corn (Zea mays L.) N rate experiments involving eight N treatments conducted in four US Midwest states in 2015 and 2016 were used for this study. A proximal RapidSCAN CS-45 active canopy sensor was used to collect corn canopy reflectance data around the V9 developmental growth stage. The utility of vegetation indices and ancillary data for predicting corn aboveground biomass, plant N concentration, plant N uptake, and NNI was evaluated using singular variable regression and machine learning methods. The results indicated that when the genetic, environmental, and management data were used together with the active canopy sensor data, corn N status indicators could be more reliably predicted either using support vector regression (R2 = 0.74–0.90 for prediction) or random forest regression models (R2 = 0.84–0.93 for prediction), as compared with using the best-performing single vegetation index or using a normalized difference vegetation index (NDVI) and normalized difference red edge (NDRE) together (R2 \u3c 0.30). The N diagnostic accuracy based on the NNI was 87% using the data fusion approach with random forest regression (kappa statistic = 0.75), which was better than the result of a support vector regression model using the same inputs. The NDRE index was consistently ranked as the most important variable for predicting all the four corn N status indicators, followed by the preplant N rate. It is concluded that incorporating genetic, environmental, and management information with canopy sensing data can significantly improve in-season corn N status prediction and diagnosis across diverse soil and weather conditions

    Clinical and Research Considerations for Patients with Hypertensive Acute Heart Failure

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    Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF

    Phase structures of strong coupling lattice QCD with finite baryon and isospin density

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    Quantum chromodynamics (QCD) at finite temperature (T), baryon chemical potential (\muB) and isospin chemical potential (\muI) is studied in the strong coupling limit on a lattice with staggered fermions. With the use of large dimensional expansion and the mean field approximation, we derive an effective action written in terms of the chiral condensate and pion condensate as a function of T, \muB and \muI. The phase structure in the space of T and \muB is elucidated, and simple analytical formulas for the critical line of the chiral phase transition and the tricritical point are derived. The effects of a finite quark mass (m) and finite \muI on the phase diagram are discussed. We also investigate the phase structure in the space of T, \muI and m, and clarify the correspondence between color SU(3) QCD with finite isospin density and color SU(2) QCD with finite baryon density. Comparisons of our results with those from recent Monte Carlo lattice simulations on finite density QCD are given.Comment: 18 pages, 6 figures, revtex4; some discussions are clarified, version to appear in Phys. Rev.

    A Public–Industry Partnership for Enhancing Corn Nitrogen Research and Datasets: Project Description, Methodology, and Outcomes

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    Due to economic and environmental consequences of N lost from fertilizer applications in corn (Zea mays L.), considerable public and industry attention has been devoted to the development of N decision tools. Needed are research and databases and associated metadata, at numerous locations and years to represent a wide geographic range of soil and weather scenarios, for evaluating tool performance. The goals of this research were to conduct standardized corn N rate response field studies to evaluate the performance of multiple public-domain N decision tools across diverse soils and environmental conditions, develop and publish new agronomic science for improved crop N management, and train new scientists. The geographic scope, scale, and unique collaborative arrangement warrant documenting details of this research. The objectives of this paper are to describe how the research was undertaken, reasons for the methods, and the project’s anticipated value. The project was initiated in a partnership between eight U.S. Midwest land-grant universities, USDA-ARS, and DuPont Pioneer. Research using a standardized protocol was conducted over the 2014 through 2016 growing seasons, yielding a total of 49 sites. Preliminary observations of soil and crop variables measured from each site revealed a magnitude of differences in soil properties (e.g., texture and organic matter) as well as differences in agronomic and economic responses to applied N. The project has generated a valuable dataset across a wide array of weather and soils that allows investigators to perform robust evaluation of N use in corn and N decision tools

    Report on the International Colloquium on Cardio-Oncology (Rome, 12–14 March 2014)

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    Cardio-oncology is a relatively new discipline that focuses on the cardiovascular sequelae of anti-tumour drugs. As any other young adolescent discipline, cardio-oncology struggles to define its scientific boundaries and to identify best standards of care for cancer patients or survivors at risk of cardiovascular events. The International Colloquium on Cardio-Oncology was held in Rome, Italy, 12–14 March 2014, with the aim of illuminating controversial issues and unmet needs in modern cardio-oncology. This colloquium embraced contributions from different kind of disciplines (oncology and cardiology but also paediatrics, geriatrics, genetics, and translational research); in fact, cardio-oncology goes way beyond the merging of cardiology with oncology. Moreover, the colloquium programme did not review cardiovascular toxicity from one drug or the other, rather it looked at patients as we see them in their fight against cancer and eventually returning to everyday life. This represents the melting pot in which anti-cancer therapies, genetic backgrounds, and risk factors conspire in producing cardiovascular sequelae, and this calls for screening programmes and well-designed platforms of collaboration between one key professional figure and another. The International Colloquium on Cardio-Oncology was promoted by the Menarini International Foundation and co-chaired by Giorgio Minotti (Rome), Joseph R Carver (Philadelphia, Pennsylvania, United States), and Steven E Lipshultz (Detroit, Michigan, United States). The programme was split into five sessions of broad investigational and clinical relevance (what is cardiotoxicity?, cardiotoxicity in children, adolescents, and young adults, cardiotoxicity in adults, cardiotoxicity in special populations, and the future of cardio-oncology). Here, the colloquium chairs and all the session chairs briefly summarised what was said at the colloquium. Topics and controversies were reported on behalf of all members of the working group of the International Colloquium on Cardio-Oncology
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