A hot cocoon in the ultralong GRB 130925A: hints of a PopIII-like progenitor in a low density wind environment

GRB 130925A is a peculiar event characterized by an extremely long gamma-ray duration ($\approx$7 ks), as well as dramatic flaring in the X-rays for $\approx$20 ks. After this period, its X-ray afterglow shows an atypical soft spectrum with photon index $\Gamma$$\sim$4, as observed by Swift and Chandra, until $\approx 10^7$ s, when XMM-Newton observations uncover a harder spectral shape with $\Gamma$$\sim$2.5, commonly observed in GRB afterglows. We find that two distinct emission components are needed to explain the X-ray observations: a thermal component, which dominates the X-ray emission for several weeks, and a non-thermal component, consistent with a typical afterglow. A forward shock model well describes the broadband (from radio to X-rays) afterglow spectrum at various epochs. It requires an ambient medium with a very low density wind profile, consistent with that expected from a low-metallicity blue supergiant (BSG). The thermal component has a remarkably constant size and a total energy consistent with those expected by a hot cocoon surrounding the relativistic jet. We argue that the features observed in this GRB (its ultralong duration, the thermal cocoon, and the low density wind environment) are associated with a low metallicity BSG progenitor and, thus, should characterize the class of ultralong GRBs.Comment: 6 pgs, 3 figs, fig1 revised, ApJL in pres

2018 GJMPP Monograph Series: Grace Jordan McFadden Professors Program

The Grace Jordan McFadden Professors Program (GJMPP), formerly the African American Professors Program (AAPP)/Carolina Diversity Professors Program (CDPP) at the University of South Carolina, is honored to publish its seventeenth edition of this annual monograph series. GJMPP recognizes the significance of offering its scholars a venue through which they have the opportunity to engage in research and to publish their refereed papers that continually contribute to their respective academic areas. Parallel with the publication of their manuscripts is a venue to gain visibility among colleagues throughout postsecondary institutions at national and international levels. Scholars who have contributed papers for this monograph are acknowledged for embracing the value of including this responsibility within their doctoral milieu. Writing across disciplines adds broadly to the intellectual diversity of these manuscripts. From neophytes to quite experienced individuals, the chapters have been researched and written with vigor. Founded in 1997 through the Department of Educational Leadership and Policies in the College of Education, AAPP was designed originally to address the under-representation of African American professors on college and university campuses. Its mission is to expand the pool of these professors in critical academic and research areas. Sponsored historically by the University of South Carolina, the W. K. Kellogg Foundation, and the South Carolina General Assembly, the program recruits doctoral students for disciplines in which African Americans and others are underrepresented among faculty in higher education. The continuation of this monograph series is seen as responding to a window of opportunity to be sensitive to an academic expectation of graduates as they pursue career placement and, at the same time, to allow for the dissemination of products of scholarship to a broader community. The importance of this series has been voiced by one of our 2002 AAPP graduates, Dr. Shundelle LaTjuan Dogan, formerly an Administrative Fellow at Harvard University, a Program Officer for the Southern Education Foundation, and a Program Officer for the Arthur M. Blank Foundation in Atlanta, Georgia. She recently completed an appointment as Corporate Citizenship and Corporate Affairs Manager for IBM International Business Machines in Atlanta and is currently a consultant with a focus on philanthropy and social impact. She is currently Assistant Vice President for Social Impact and Innovation at Emory University. Dr. Dogan has written an impressive Foreword for the 2014 monograph. In a personal letter, which is cited in an earlier monograph, Dr. Dogan penned: “One thing in particular that I want to thank you for is having the African American Professors Program scholars publish articles for the monograph. I have to admit that writing the articles seemed like extra work at the time. However, in my recent interview process, organizations have asked me for samples of my writing. Including an article from a published monograph helped to make my portfolio much more impressive. You were ‘right on target’ in having us do the monograph series” (AAPP 2003, Monograph, p. xi). The Grace Jordan McFadden Professors Program purports to advance the tradition of spearheading international scholarship in higher education as evidenced through inspiration from this group of interdisciplinary manuscripts. I hope that you will envision these published papers to serve as an invaluable contribution to your own professional and career enhancement. John McFadden, PhD The Benjamin Elijah Mays Distinguished Professor Emeritus Director, Grace Jordan McFadden Professors Program University of South Carolina Columbia, South Carolinahttps://scholarcommons.sc.edu/mcfadden_monographs/1010/thumbnail.jp

Personality judgments from everyday images of faces

The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: an ESRC studentship [ES/I900748/1] and postdoctoral research support from the Australian Research Council Centre of Excellence in Cognition and its Disorders, University of Western Australia (CE110001021), to the first author. The work was completed while the first author was at the University of York, UK. We thank Richard Vernon for calculating the attributes used in Study 2.Peer reviewedPublisher PD

Genetic and Clinical Predictors of Age of ESKD in Individuals With Autosomal Dominant Tubulointerstitial Kidney Disease Due to UMOD Mutations

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Effects of Ploidy and Recombination on Evolution of Robustness in a Model of the Segment Polarity Network

Many genetic networks are astonishingly robust to quantitative variation, allowing these networks to continue functioning in the face of mutation and environmental perturbation. However, the evolution of such robustness remains poorly understood for real genetic networks. Here we explore whether and how ploidy and recombination affect the evolution of robustness in a detailed computational model of the segment polarity network. We introduce a novel computational method that predicts the quantitative values of biochemical parameters from bit sequences representing genotype, allowing our model to bridge genotype to phenotype. Using this, we simulate 2,000 generations of evolution in a population of individuals under stabilizing and truncation selection, selecting for individuals that could sharpen the initial pattern of engrailed and wingless expression. Robustness was measured by simulating a mutation in the network and measuring the effect on the engrailed and wingless patterns; higher robustness corresponded to insensitivity of this pattern to perturbation. We compared robustness in diploid and haploid populations, with either asexual or sexual reproduction. In all cases, robustness increased, and the greatest increase was in diploid sexual populations; diploidy and sex synergized to evolve greater robustness than either acting alone. Diploidy conferred increased robustness by allowing most deleterious mutations to be rescued by a working allele. Sex (recombination) conferred a robustness advantage through “survival of the compatible”: those alleles that can work with a wide variety of genetically diverse partners persist, and this selects for robust alleles

Autoantibody Epitope Spreading in the Pre-Clinical Phase Predicts Progression to Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a prototypical autoimmune arthritis affecting nearly 1% of the world population and is a significant cause of worldwide disability. Though prior studies have demonstrated the appearance of RA-related autoantibodies years before the onset of clinical RA, the pattern of immunologic events preceding the development of RA remains unclear. To characterize the evolution of the autoantibody response in the preclinical phase of RA, we used a novel multiplex autoantigen array to evaluate development of the anti-citrullinated protein antibodies (ACPA) and to determine if epitope spread correlates with rise in serum cytokines and imminent onset of clinical RA. To do so, we utilized a cohort of 81 patients with clinical RA for whom stored serum was available from 1–12 years prior to disease onset. We evaluated the accumulation of ACPA subtypes over time and correlated this accumulation with elevations in serum cytokines. We then used logistic regression to identify a profile of biomarkers which predicts the imminent onset of clinical RA (defined as within 2 years of testing). We observed a time-dependent expansion of ACPA specificity with the number of ACPA subtypes. At the earliest timepoints, we found autoantibodies targeting several innate immune ligands including citrullinated histones, fibrinogen, and biglycan, thus providing insights into the earliest autoantigen targets and potential mechanisms underlying the onset and development of autoimmunity in RA. Additionally, expansion of the ACPA response strongly predicted elevations in many inflammatory cytokines including TNF-α, IL-6, IL-12p70, and IFN-γ. Thus, we observe that the preclinical phase of RA is characterized by an accumulation of multiple autoantibody specificities reflecting the process of epitope spread. Epitope expansion is closely correlated with the appearance of preclinical inflammation, and we identify a biomarker profile including autoantibodies and cytokines which predicts the imminent onset of clinical arthritis

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant