The E. coli chromosome is condensed into insulated regions termed macrodomains (MDs), which are essential for genomic packaging. How chromosomal MDs are specifically organized and compacted is unknown. Here, we report studies revealing the molecular basis for Terminus-containing (Ter) chromosome condensation by the Ter-specific factor MatP. MatP contains a tripartite fold with a four-helix bundle DNA-binding motif, ribbon-helix-helix and C-terminal coiled-coil. Strikingly, MatP-matS structures show that the MatP coiled-coils form bridged tetramers that flexibly link distant matS sites. Atomic force microscopy and electron microscopy studies demonstrate that MatP alone loops DNA. Mutation of key coiled-coil residues destroys looping and causes a loss of Ter condensation in vivo. Thus, these data reveal the molecular basis for a protein-mediated DNA-bridging mechanism that mediates condensation of a large chromosomal domain in enterobacteria.
The authors note that on page 13064, right column, first full paragraph, lines 4-7, "Some of the climatic events linked to such concerns are the severe droughts experienced by the Amazon basin in 2005 and 2010, which reportedly reduced tropical forest NPP by 1.6 to 2.2 PgC/y and increased tree mortality (50, 51)" should instead appear as "Some of the climatic events linked to such concerns are the severe droughts experienced by the Amazon basin in 2005 and 2010, which reportedly reduced tropical forest NPP and increased tree mortality by a total biomass carbon loss of 1.6 to 2.2 PgC (50, 51)."On page 13064, right column, first full paragraph, lines 12-17, "Assuming that the large reductions of tropical NPP reported previously (50, 51) are realistic, the absence of marked variations of the global CO 2 growth rate after the 2005 and 2010 Amazon droughts may imply that the drought conditions also coincidently reduced tropical Rh along with NPP, resulting in (relatively) small NEE anomalies" should instead appear as "Assuming that the large reductions of tropical forest biomass reported previously (50, 51) are realistic, the absence of marked variations of the global CO 2 growth rate after the 2005 and 2010 Amazon droughts may imply that the drought conditions also coincidently reduced tropical Rh along with NPP, resulting in (relatively) small NEE anomalies."These changes do not affect the conclusions of the article.
The quality of pediatric resuscitative care delivered across the spectrum of emergency departments (EDs) in the United States is poorly described. In a recent study, more than 4000 EDs completed the Pediatric Readiness Survey (PRS); however, the correlation of PRS scores with the quality of simulated or real patient care has not been described. OBJECTIVE To measure and compare the quality of resuscitative care delivered to simulated pediatric patients across a spectrum of EDs and to examine the correlation of PRS scores with quality measures. DESIGN, SETTING, AND PARTICIPANTS This prospective multicenter cohort study evaluated 58 interprofessional teams in their native pediatric or general ED resuscitation bays caring for a series of 3 simulated critically ill patients (sepsis, seizure, and cardiac arrest). MAIN OUTCOMES AND MEASURES A composite quality score (CQS) was measured as the sum of 4 domains: (1) adherence to sepsis guidelines, (2) adherence to cardiac arrest guidelines, (3) performance on seizure resuscitation, and (4) teamwork. Pediatric Readiness Survey scores and health care professional demographics were collected as independent data. Correlations were explored between CQS and individual domain scores with PRS. RESULTS Overall, 58 teams from 30 hospitals participated (8 pediatric EDs [PEDs], 22 general EDs [GEDs]). The mean CQS was 71 (95% CI, 68-75); PEDs had a higher mean CQS (82; 95% CI, 79-85) vs GEDs (66; 95% CI, 63-69) and outperformed GEDs in all domains. However, when using generalized estimating equations to estimate CQS controlling for clustering of the data, PED status did not explain a higher CQS (β = 4.28; 95% CI, −4.58 to 13.13) while the log of pediatric patient volume did explain a higher CQS (β = 9.57; 95% CI, 2.64-16.49). The correlation of CQS to PRS was moderate (r = 0.51; P < .001). The correlation was weak for cardiac arrest (r = 0.24; P = .07), weak for sepsis (ρ = 0.45; P < .001) and seizure (ρ = 0.43; P = .001), and strong for teamwork (ρ = 0.71; P < .001). CONCLUSIONS AND RELEVANCE This multicenter study noted significant differences in the quality of simulated pediatric resuscitative care across a spectrum of EDs. The CQS was higher in PEDs compared with GEDs. However, when controlling for pediatric patient volume and other variables in a multivariable model, PED status does not explain a higher CQS while pediatric patient volume does. The correlation of the PRS was moderate for simulation-based measures of quality.
All cells must sense and adapt to changing nutrient availability. However, detailed molecular mechanisms coordinating such regulatory pathways remain poorly understood. In Bacillus subtilis, nitrogen homeostasis is controlled by a unique circuitry composed of the regulator TnrA, which is deactivated by feedback-inhibited glutamine synthetase (GS) during nitrogen excess and stabilized by GlnK upon nitrogen depletion, and the repressor GlnR. Here we describe a complete molecular dissection of this network. TnrA and GlnR, the global nitrogen homeostatic transcription regulators, are revealed as founders of a new structural family of dimeric DNA-binding proteins with C-terminal, flexible, effector-binding sensors that modulate their dimerization. Remarkably, the TnrA sensor domains insert into GS intersubunit catalytic pores, destabilizing the TnrA dimer and causing an unprecedented GS dodecamer-to-tetradecamer conversion, which concomitantly deactivates GS. In contrast, each subunit of the GlnK trimer “templates” active TnrA dimers. Unlike TnrA, GlnR sensors mediate an autoinhibitory dimer-destabilizing interaction alleviated by GS, which acts as a GlnR chaperone. Thus, these studies unveil heretofore unseen mechanisms by which inducible sensor domains drive metabolic reprograming in the model Gram-positive bacterium B. subtilis.
, for the INSPIRE LP investigators abstract BACKGROUND AND OBJECTIVE: Simulation-based skill trainings are common; however, optimal instructional designs that improve outcomes are not well specified. We explored the impact of just-in-time and just-in-place training (JIPT) on interns' infant lumbar puncture (LP) success.
There was no increase in triage accuracy when paramedics evaluating disaster victims used telemedicine, and telemedicine required more time than conventional triage. There are a number of obstacles to available technology that, if overcome, might improve the utility of telemedicine in disaster response.
Our collaborative improvement program that involved simulation was associated with improvement in pediatric readiness scores in 10 EDs participating statewide. Future work will focus on further expanding of the network and establishing a national model for pediatric readiness improvement.
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