Characterization of a protein-protein interaction within the SigO-RsoA two-subunit σ factor: the σ70 region 2.3-like segment of RsoA mediates interaction with SigO.

σ factors are single subunit general transcription factors that reversibly bind core RNA polymerase and mediate gene-specific transcription in bacteria. Previously, an atypical two-subunit σ factor was identified that activates transcription from a group of related promoters in Bacillus subtilis. Both of the subunits, named SigO and RsoA, share primary sequence similarity with the canonical σ70 family of σ factors and interact with each other and with RNA polymerase subunits. Here we show that the σ70 region 2.3-like segment of RsoA is unexpectedly sufficient for interaction with the amino-terminus of SigO and the ß' subunit. A mutational analysis of RsoA identified aromatic residues conserved amongst all RsoA homologues, and often amongst canonical σ factors, that are particularly important for the SigO-RsoA interaction. In a canonical σ factor, region 2.3 amino acids bind non-template strand DNA, trapping the promoter in a single-stranded state required for initiation of transcription. Accordingly, we speculate that RsoA region 2.3 protein-binding activity likely arose from a motif that, at least in its ancestral protein, participated in DNA-binding interactions.

Risk of Cardiovascular Events After COVID-19.

We aimed to determine absolute and relative risks of either symptomatic or asymptomatic SARS-CoV-2 infection for late cardiovascular (CV) events and all-cause mortality. We conducted a retrospective double cohort study of patients with either symptomatic or asymptomatic SARS-CoV-2 infection (COVID-19+ cohort) and its documented absence (COVID-19- cohort). The study investigators drew a simple random sample of records from all patients under the Oregon Health & Science University Healthcare (n = 65,585), with available COVID-19 test results, performed March 1, 2020 to September 13, 2020. Exclusion criteria were age <18 years and no established Oregon Health & Science University care. The primary outcome was a composite of CV morbidity and mortality. All-cause mortality was the secondary outcome. The study population included 1,355 patients (mean age 48.7 ± 20.5 years; 770 women [57%], 977 White non-Hispanic [72%]; 1,072 ensured [79%]; 563 with CV disease history [42%]). During a median 6 months at risk, the primary composite outcome was observed in 38 of 319 patients who were COVID-19+ (12%) and 65 of 1,036 patients who were COVID-19- (6%). In the Cox regression, adjusted for demographics, health insurance, and reason for COVID-19 testing, SARS-CoV-2 infection was associated with the risk for primary composite outcome (hazard ratio 1.71, 95% confidence interval 1.06 to 2.78, p = 0.029). Inverse probability-weighted estimation, conditioned for 31 covariates, showed that for every patient who was COVID-19+, the average time to all-cause death was 65.5 days less than when all these patients were COVID-19-: average treatment effect on the treated -65.5 (95% confidence interval -125.4 to -5.61) days, p = 0.032. In conclusion, either symptomatic or asymptomatic SARS-CoV-2 infection is associated with an increased risk for late CV outcomes and has a causal effect on all-cause mortality in a late post-COVID-19 period.

The benefits of CRM: is your home care agency missing out?

Home care executives today have at their disposal all the means necessary to manage information and strengthen relationships with customers, thanks to innovative customer relationship management (CRM) tools, Adam D. Bishop explains.