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Finally, since many pseudoknots have high affinity for S1, we predicted similar pseudoknots in non-homologous type I toxin-antitoxin systems that exhibit features similar to that of tisB-IstR1, suggesting a shared requirement for standby acting at great distances.The Mouse Genome Database (MGD; http//www.informatics.jax.org) is the community model organism knowledgebase for the laboratory mouse, a widely used animal model for comparative studies of the genetic and genomic basis for human health and disease. find more MGD is the authoritative source for biological reference data related to mouse genes, gene functions, phenotypes and mouse models of human disease. MGD is the primary source for official gene, allele, and mouse strain nomenclature based on the guidelines set by the International Committee on Standardized Nomenclature for Mice. MGD's biocuration scientists curate information from the biomedical literature and from large and small datasets contributed directly by investigators. In this report we describe significant enhancements to the content and interfaces at MGD, including (i) improvements in the Multi Genome Viewer for exploring the genomes of multiple mouse strains, (ii) inclusion of many more mouse strains and new mouse strain pages with extended query options and (iii) integration of extensive data about mouse strain variants. We also describe improvements to the efficiency of literature curation processes and the implementation of an information portal focused on mouse models and genes for the study of COVID-19.Histones are substrates of the SUMO (small ubiquitin-like modifier) conjugation pathway. Several reports suggest histone sumoylation affects transcription negatively, but paradoxically, our genome-wide analysis shows the modification concentrated at many active genes. We find that trans-tail regulation of histone-H2B ubiquitylation and H3K4 di-methylation potentiates subsequent histone sumoylation. Consistent with the known control of the Set3 histone deacetylase complex (HDAC) by H3K4 di-methylation, histone sumoylation directly recruits the Set3 complex to both protein-coding and noncoding RNA (ncRNA) genes via a SUMO-interacting motif in the HDAC Cpr1 subunit. The altered gene expression profile caused by reducing histone sumoylation matches well to the profile in cells lacking Set3. Histone H2B sumoylation and the Set3 HDAC coordinately suppress cryptic ncRNA transcription initiation internal to mRNA genes. Our results reveal an elaborate co-transcriptional histone crosstalk pathway involving the consecutive ubiquitylation, methylation, sumoylation and deacetylation of histones, which maintains transcriptional fidelity by suppressing spurious transcription.

Disparities in representation between sexes have been shown at multiple career stages in medicine despite increasing representation in the overall physician workforce.

To assess sex representation of applicants to the Canadian R-1 entry match for postgraduate training programs from 1995 to 2019, comparing distribution between different specialties as well as applied vs matched applicants.

This cross-sectional analysis of aggregate data provided by the Canadian Resident Matching Service between 1995 and 2019 analyzed aggregate data for the Canadian R-1 residency match from 1995 through 2019.

Applicant sex as reported in the Canadian Resident Matching Service database.

The sex representation of applicants was compared and the longitudinal trends in sex representation were analyzed by specialty between 1995 and 2019. The sex representation of overall applicants to the Canadian R-1 entry match were compared with matched applicants, and both were stratified by specialty.

A total of 48 424 applicants we, 1.19; 95% CI, 1.10-1.28; P < .001).

Increasing representation of female residency applicants over time was seen in some, but not all, medical specialties in Canada, and sex-based differences in successful match rates were observed in some specialties. The reasons for these disparities require further investigation for corrective strategies to be identified.

Increasing representation of female residency applicants over time was seen in some, but not all, medical specialties in Canada, and sex-based differences in successful match rates were observed in some specialties. The reasons for these disparities require further investigation for corrective strategies to be identified.

The population impact of modifying obesity and other key risk factors for hyperuricemia has been estimated in cross-sectional studies; however, the proportion of incident gout cases (a clinical end point) that could be prevented by modifying such factors has not been evaluated.

To estimate the proportion of incident gout cases that could be avoided through simultaneous modification of obesity and other key risk factors.

The Health Professionals Follow-up Study is a US prospective cohort study of 51 529 male health professionals enrolled in 1986 and followed up through questionnaires every 2 years through 2012. Self-reported gout cases were confirmed through June 2015. Clean and complete data used for this analysis were available in June 2016, with statistical analyses performed from July 2016 to July 2019.

From data collected in the validated questionnaires, men were categorized to low-risk groups according to combinations of the following 4 factors normal body mass index (BMI [calculated as weight inly lower and not significant (5% [95% CI, 0%-47%]).

The findings of this cohort study suggest that addressing excess adiposity and other key modifiable factors has the potential to prevent the majority of incident gout cases among men. Men with obesity may not benefit from other modifications unless weight loss is addressed.

The findings of this cohort study suggest that addressing excess adiposity and other key modifiable factors has the potential to prevent the majority of incident gout cases among men. Men with obesity may not benefit from other modifications unless weight loss is addressed.

Intensive lifestyle interventions focused on diet and exercise can reduce weight and improve diabetes management. However, the long-term effects on health care use and spending are unclear, especially for public payers.

To estimate the association of effective intensive lifestyle intervention for weight loss with long-term health care use and Medicare spending.

This ancillary study used data from the Look AHEAD randomized clinical trial, which randomized participants with type 2 diabetes to an intensive lifestyle intervention or control group (ie, diabetes support and education), provided ongoing intervention from 2001 to 2012, and demonstrated improved diabetes management and reduced health care costs during the intervention. This study compared Medicare data between study arms from 2012 to 2015 to determine whether the intervention was associated with persistent reductions in health care spending.

Starting in 2001, Look AHEAD's intervention group participated in sessions with lifestyle counselors, dieticians, exercise specialists, and behavioral therapists with the goal of reducing weight 7% in the first year.

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