Highly Contiguous Assemblies of 101 Drosophilid Genomes

Over 100 years of studies in Drosophila melanogaster and related species in the genus Drosophila have facilitated key discoveries in genetics, genomics, and evolution. While high-quality genome assemblies exist for several species in this group, they only encompass a small fraction of the genus. Recent advances in long-read sequencing allow high-quality genome assemblies for tens or even hundreds of species to be efficiently generated. Here, we utilize Oxford Nanopore sequencing to build an open community resource of genome assemblies for 101 lines of 93 drosophilid species encompassing 14 species groups and 35 sub-groups. The genomes are highly contiguous and complete, with an average contig N50 of 10.5 Mb and greater than 97% BUSCO completeness in 97/101 assemblies. We show that Nanopore-based assemblies are highly accurate in coding regions, particularly with respect to coding insertions and deletions. These assemblies, along with a detailed laboratory protocol and assembly pipelines, are released as a public resource and will serve as a starting point for addressing broad questions of genetics, ecology, and evolution at the scale of hundreds of species

Highly contiguous assemblies of 101 drosophilid genomes

Over 100 years of studies in Drosophila melanogaster and related species in the genus Drosophila have facilitated key discoveries in genetics, genomics, and evolution. While high-quality genome assemblies exist for several species in this group, they only encompass a small fraction of the genus. Recent advances in long-read sequencing allow high-quality genome assemblies for tens or even hundreds of species to be efficiently generated. Here, we utilize Oxford Nanopore sequencing to build an open community resource of genome assemblies for 101 lines of 93 drosophilid species encompassing 14 species groups and 35 sub-groups. The genomes are highly contiguous and complete, with an average contig N50 of 10.5 Mb and greater than 97% BUSCO completeness in 97/101 assemblies. We show that Nanopore-based assemblies are highly accurate in coding regions, particularly with respect to coding insertions and deletions. These assemblies, along with a detailed laboratory protocol and assembly pipelines, are released as a public resource and will serve as a starting point for addressing broad questions of genetics, ecology, and evolution at the scale of hundreds of species

Carnegie Supernova Project-I and -II: Measurements of H0H_0 using Cepheid, TRGB, and SBF Distance Calibration to Type Ia Supernovae

We present an analysis of Type Ia Supernovae (SNe~Ia) from both the Carnegie Supernova Project~I (CSP-I) and II (CSP-II), and extend the Hubble diagram from the optical to the near-infrared wavelengths ($uBgVriYJH$). We calculate the Hubble constant, $H_0$, using various distance calibrators: Cepheids, Tip of the Red Giant Branch (TRGB), and Surface Brightness Fluctuations (SBF). Combining all methods of calibrations, we derive $\rm H_0=71.76 \pm 0.58 \ (stat) \pm 1.19 \ (sys) \ km \ s^{-1} \ Mpc^{-1}$from$B$-band, and$\rm H_0=73.22 \pm 0.68 \ (stat) \pm 1.28 \ (sys) \ km \ s^{-1} \ Mpc^{-1}$from$H$-band. By assigning equal weight to the Cepheid, TRGB, and SBF calibrators, we derive the systematic errors required for consistency in the first rung of the distance ladder, resulting in a systematic error of$1.2\sim 1.3 \rm \ km \ s^{-1} \ Mpc^{-1}$in$H_0$. As a result, relative to the statistics-only uncertainty, the tension between the late-time$H_0$we derive by combining the various distance calibrators and the early-time$H_0$from the Cosmic Microwave Background is reduced. The highest precision in SN~Ia luminosity is found in the$Y$band ($0.12\pm0.01$mag), as defined by the intrinsic scatter ($\sigma_{int}$). We revisit SN~Ia Hubble residual-host mass correlations and recover previous results that these correlations do not change significantly between the optical and the near-infrared wavelengths. Finally, SNe~Ia that explode beyond 10 kpc from their host centers exhibit smaller dispersion in their luminosity, confirming our earlier findings. Reduced effect of dust in the outskirt of hosts may be responsible for this effect.Comment: Revised calculations are made. Will be resubmitted to Ap

Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis

The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (Cindex) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction

Studying Children's Intrapersonal Emotion Regulation Strategies from the Process Model of Emotion Regulation

peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=vgnt2

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data