Degntemple6140

The song sparrow, Melospiza melodia, is one of the most widely distributed species of songbirds found in North America. It has been used in a wide range of behavioral and ecological studies. This species' pronounced morphological and behavioral diversity across populations makes it a favorable candidate in several areas of biomedical research. We have generated a high-quality de novo genome assembly of M. melodia using Illumina short read sequences from genomic and in vitro proximity-ligation libraries. The assembled genome is 978.3 Mb, with a physical coverage of 24.9×, N50 scaffold size of 5.6 Mb and N50 contig size of 31.7 Kb. Our genome assembly is highly complete, with 87.5% full-length genes present out of a set of 4,915 universal single-copy orthologs present in most avian genomes. selleckchem We annotated our genome assembly and constructed 15,086 gene models, a majority of which have high homology to related birds, Taeniopygia guttata and Junco hyemalis In total, 83% of the annotated genes are assigned with putative functions. Furthermore, only ∼7% of the genome is found to be repetitive; these regions and other non-coding functional regions are also identified. The high-quality M. melodia genome assembly and annotations we report will serve as a valuable resource for facilitating studies on genome structure and evolution that can contribute to biomedical research and serve as a reference in population genomic and comparative genomic studies of closely related species. Copyright © The Author(s) 2020. Published by the Genetics Society of America.The evolution of drug resistance in pathogens such as HIV is an important and widely known example in the field of evolutionary medicine. Here, we focus on a unique data set from the late 1990s with multiple viral sequences from multiple time points in 118 patients. We study patterns of evolutionary dynamics in the viral populations in these patients who were treated with Reverse Transcriptase Inhibitors and Protease Inhibitors in the late 1990s. Specifically, we aim to visualize and analyze examples of population genetic processes such as selective sweeps and clonal interference. The figures and descriptions in this paper can be used in evolution and population genetics classes. We show and analyze a wide variety of patterns, specifically soft sweeps, hard sweeps, softening sweeps and hardening sweeps, simultaneous sweeps, accumulation of mutations and clonal interference. Copyright © The Author(s) 2020. Published by the Genetics Society of America.OBJECTIVES Accurately predicting and reducing risk of unplanned readmissions (URs) in pediatric care remains difficult. We sought to develop a set of accurate algorithms to predict URs within 3, 7, and 30 days of discharge from inpatient admission that can be used before the patient is discharged from a current hospital stay. METHODS We used the Children's Hospital Association Pediatric Health Information System to identify a large retrospective cohort of 1 111 323 children with 1 321 376 admissions admitted to inpatient care at least once between January 1, 2016, and December 31, 2017. We used gradient boosting trees (XGBoost) to accommodate complex interactions between these predictors. RESULTS In the full cohort, 1.6% of patients had at least 1 UR in 3 days, 2.4% had at least 1 UR in 7 days, and 4.4% had at least 1 UR within 30 days. Prediction model discrimination was strongest for URs within 30 days (area under the curve [AUC] = 0.811; 95% confidence interval [CI] 0.808-0.814) and was nearly identical for UR risk prediction within 3 days (AUC = 0.771; 95% CI 0.765-0.777) and 7 days (AUC = 0.778; 95% CI 0.773-0.782), respectively. Using these prediction models, we developed a publicly available pediatric readmission risk scores prediction tool that can be used before or during discharge planning. CONCLUSIONS Risk of pediatric UR can be predicted with information known before the patient's discharge and that is easily extracted in many electronic medical record systems. This information can be used to predict risk of readmission to support hospital-discharge-planning resources. Copyright © 2020 by the American Academy of Pediatrics.Hypoxia selectively enhances mRNA translation despite suppressed mammalian target of rapamycin complex 1 activity, contributing to gene expression reprogramming that promotes metastasis and survival of cancer cells. Little is known about how this paradoxical control of translation occurs. Here, we report a new pathway that links hypoxia to selective mRNA translation. Transglutaminase 2 (TG2) is a hypoxia-inducible factor 1-inducible enzyme that alters the activity of substrate proteins by polyamination or crosslinking. Under hypoxic conditions, TG2 polyaminated eukaryotic translation initiation factor 4E (eIF4E)-bound eukaryotic translation initiation factor 4E-binding proteins (4EBPs) at conserved glutamine residues. 4EBP1 polyamination enhances binding affinity for Raptor, thereby increasing phosphorylation of 4EBP1 and cap-dependent translation. Proteomic analyses of newly synthesized proteins in hypoxic cells revealed that TG2 activity preferentially enhanced the translation of a subset of mRNA containing G/C-rich 5'UTRs but not upstream ORF or terminal oligopyrimidine motifs. These results indicate that TG2 is a critical regulator in hypoxia-induced selective mRNA translation and provide a promising molecular target for the treatment of cancers. © 2020 Cho et al.Viruses are the most abundant biological entities on Earth and play key roles in host ecology, evolution, and horizontal gene transfer. Despite recent progress in viral metagenomics, the inherent genetic complexity of virus populations still poses technical difficulties for recovering complete virus genomes from natural assemblages. To address these challenges, we developed an assembly-free, single-molecule nanopore sequencing approach, enabling direct recovery of complete virus genome sequences from environmental samples. Our method yielded thousands of full-length, high-quality draft virus genome sequences that were not recovered using standard short-read assembly approaches. Additionally, our analyses discriminated between populations whose genomes had identical direct terminal repeats versus those with circularly permuted repeats at their termini, thus providing new insight into native virus reproduction and genome packaging. Novel DNA sequences were discovered, whose repeat structures, gene contents, and concatemer lengths suggest they are phage-inducible chromosomal islands, which are packaged as concatemers in phage particles, with lengths that match the size ranges of co-occurring phage genomes. Our new virus sequencing strategy can provide previously unavailable information about the genome structures, population biology, and ecology of naturally occurring viruses and viral parasites. © 2020 Beaulaurier et al.; Published by Cold Spring Harbor Laboratory Press.BACKGROUND To determine if prehospital blood glucose could be added to National Early Warning Score (NEWS) for improved identification of risk of short-term mortality. METHODS Retrospective observational study (2008-2015) of adult patients seen by emergency medical services in Helsinki metropolitan area for whom all variables for calculation of NEWS and a blood glucose value were available. Survival of 24 hours and 30 days were determined. The NEWS parameters and glucose were tested by multivariate logistic regression model. Based on ORs we formed NEWSgluc model with hypoglycaemia (≤3.0 mmol/L) 3, normoglycaemia 0 and hyperglycaemia (≥11.1 mmol/L) 1 points. The scores from NEWS and NEWSgluc were compared using discrimination (area under the curve), calibration (Hosmer-Lemeshow test), likelihood ratio tests and reclassification (continuous net reclassification index (cNRI)). RESULTS Data of 27 141 patients were included in the study. Multivariable regression model for NEWSgluc parameters revealed a strong association with glucose disturbances and 24-hour and 30-day mortality. Likelihood ratios (LRs) for mortality at 24 hours using a cut-off point of 15 were for NEWSgluc LR+ 17.78 and LR- 0.96 and for NEWS LR+ 13.50 and LR- 0.92. Results were similar at 30 days. Risks per score point estimation and calibration model showed glucose added benefit to NEWS at 24 hours and at 30 days. Although areas under the curve were similar, reclassification test (cNRI) showed overall improvement of classification of survivors and non-survivors at 24 days and 30 days with NEWSgluc. CONCLUSIONS Including glucose in NEWS in the prehospital setting seems to improve identification of patients at risk of death. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Refractory hypotension is one of the most common and difficult clinical problems faced by acute care clinicians, and it poses a particularly large problem to the emergency physician when a patient in undifferentiated shock arrives in the department. Angiotensin II (Ang-2) has been previously used as a vasopressor to combat shock; the feasibility of its clinical use has been reinvigorated after approval of a human synthetic formulation of the medication by the US Food and Drug Administration in 2017 and the European Medicines Agency in 2019. A thorough literature search was completed, and in this review, we discuss the discovery and development of Ang-2, its complex mechanisms of vasoconstriction, its potential adverse effects and its potential role in clinical practice for emergency physicians. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To assess whether initiation of insulin glargine (glargine), compared with initiation of neutral protamine Hagedorn (NPH) or insulin detemir (detemir), was associated with an increased risk of breast cancer in women with diabetes. RESEARCH DESIGN AND METHODS This was a retrospective new-user cohort study of female Medicare beneficiaries aged ≥65 years initiating glargine (203,159), detemir (67,012), or NPH (47,388), from September 2006 to September 2015, with follow-up through May 2017. Weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for incidence of breast cancer according to ever use, cumulative duration of use, cumulative dose of insulin, length of follow-up time, and a combination of dose and length of follow-up time. RESULTS Ever use of glargine was not associated with an increased risk of breast cancer compared with NPH (HR 0.97; 95% CI 0.88-1.06) or detemir (HR, 0.98; 95% CI 0.92-1.05). No increased risk was seen with glargine use compared with either NPH or detemir by duration of insulin use, length of follow-up, or cumulative dose of insulin. No increased risk of breast cancer was observed in medium- or high-dose glargine users compared with low-dose users. CONCLUSIONS Overall, glargine use was not associated with an increased risk of breast cancer compared with NPH or detemir in female Medicare beneficiaries. © 2020 by the American Diabetes Association.INTRODUCTION Aspects of the built environment that support physical activity are associated with better population health outcomes. Few experimental data exist to support these observations. This protocol describes the study of the creation of urban trials on cardiovascular disease (CVD)-related morbidity and mortality in a large urban centre. METHODS AND ANALYSIS Between 2008 and 2010, the city of Winnipeg, Canada, built four, paved, multiuse (eg, cycling, walking and running), two-lane trails that are 5-8 km long and span ~60 neighbourhoods. Linking a population-based health data with census and environmental data, we will perform an interrupted time series analysis to assess the impact of this natural experiment on CVD-related morbidity and mortality among individuals 30-65 years of age residing within 400-1200 m of the trail. The primary outcome of interest is a composite measure of incident major adverse CVD events (ie, CVD-related mortality, ischaemic heart disease, stroke and congestive heart failure).