The Conserved nhaAR Operon Is Drastically Divergent between B2 and Non-B2 Escherichia coli and Is Involved in Extra-Intestinal Virulence

The Escherichia coli species is divided in phylogenetic groups that differ in their virulence and commensal distribution. Strains belonging to the B2 group are involved in extra-intestinal pathologies but also appear to be more prevalent as commensals among human occidental populations. To investigate the genetic specificities of B2 sub-group, we used 128 sequenced genomes and identified genes of the core genome that showed marked difference between B2 and non-B2 genomes. We focused on the gene and its surrounding region with the strongest divergence between B2 and non-B2, the antiporter gene nhaA. This gene is part of the nhaAR operon, which is in the core genome but flanked by mobile regions, and is involved in growth at high pH and high sodium concentrations. Consistently, we found that a panel of non-B2 strains grew faster than B2 at high pH and high sodium concentrations. However, we could not identify differences in expression of the nhaAR operon using fluorescence reporter plasmids. Furthermore, the operon deletion had no differential impact between B2 and non-B2 strains, and did not result in a fitness modification in a murine model of gut colonization. Nevertheless, sequence analysis and experiments in a murine model of septicemia revealed that recombination in nhaA among B2 strains was observed in strains with low virulence. Finally, nhaA and nhaAR operon deletions drastically decreased virulence in one B2 strain. This effect of nhaAR deletion appeared to be stronger than deletion of all pathogenicity islands. Thus, a population genetic approach allowed us to identify an operon in the core genome without strong effect in commensalism but with an important role in extra-intestinal virulence, a landmark of the B2 strains

Effect of Early Erythropoietin on Retinopathy of Prematurity: A Stratified Meta-Analysis

Background: Recombinant human erythropoietin (rhEPO) lost its role in minimizing red blood cell transfusion in very preterm infants after it had been associated with severe retinopathy of prematurity (ROP). Previous systematic reviews did not stratify ROP by gestation and birth weight (BW). Objectives: The aim of this study was to investigate the effect of early prophylactic rhEPO on ROP in a stratified meta-analysis of randomized controlled trials (RCTs). Methods: The databases EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched in January 2022 and complemented by citation searching. RCTs comparing early rhEPO treatment with no treatment or placebo were selected if they were published in a peer-reviewed journal and reported ROP outcomes. Previously unpublished data were requested from the study authors to allow stratified analyses by gestational age (GA) and BW. Data were extracted and analyzed using the standard methods of the Cochrane Neonatal Review Group. Pre-specified outcomes were "ROP stage =3" (primary outcome) and "any ROP." Results: Fourteen RCTs, comprising 2,040 infants of <29 weeks of GA, were included for meta-analysis. Data syntheses showed no effects of rhEPO on ROP stage =3 or on any ROP, neither in infants of <29 weeks GA, nor in infants of <1,000 g BW, nor in any GA strata. The risk ratio (95% confidence interval) for ROP stage =3 in infants of <29 weeks of GA was 1.13 (0.84, 1.53), p = 0.41 (quality of evidence: moderate). Conclusions: The present meta-analysis detected no effects of early rhEPO on ROP in any comparison, but most stratified analyses were limited by low statistical power

Correction of non-linearity effects in detectors for electron spectroscopy

Using photoemission intensities and a detection system employed by many groups in the electron spectroscopy community as an example, we have quantitatively characterized and corrected detector non-linearity effects over the full dynamic range of the system. Non-linearity effects are found to be important whenever measuring relative peak intensities accurately is important, even in the low-countrate regime. This includes, for example, performing quantitative analyses for surface contaminants or sample bulk stoichiometries, where the peak intensities involved can differ by one or two orders of magnitude, and thus could occupy a significant portion of the detector dynamic range. Two successful procedures for correcting non-linearity effects are presented. The first one yields directly the detector efficiency by measuring a flat-background reference intensity as a function of incident x-ray flux, while the second one determines the detector response from a least-squares analysis of broad-scan survey spectra at different incident x-ray fluxes. Although we have used one spectrometer and detection system as an example, these methodologies should be useful for many other cases.Comment: 13 pages, 12 figure

Broadband Optical Serrodyne Frequency Shifting

We demonstrate serrodyne frequency shifting of light from 200 MHz to 1.2 GHz with an efficiency of better than 60 percent. The frequency shift is imparted by an electro-optic phase modulator driven by a high-frequency, high-fidelity sawtooth waveform that is passively generated by a commercially available Non-Linear Transmission Line (NLTL). We also implement a push-pull configuration using two serrodyne-driven phase modulators allowing for continuous tuning between -1.6 GHz and +1.6 GHz. Compared to competing technologies, this technique is simple and robust, and offers the largest available tuning range in this frequency band.Comment: 3 pages, 4 figure

Fermilab E791

Fermilab E791, a very high statistics charm particle experiment, recently completed its data taking at Fermilab's Tagged Photon Laboratory. Over 20 billion events were recorded through a loose transverse energy trigger and written to 8mm tape in the the 1991-92 fixed target run at Fermilab. This unprecedented data sample containing charm is being analysed on many-thousand MIP RISC computing farms set up at sites in the collaboration. A glimpse of the data taking and analysis effort is presented. We also show some preliminary results for common charm decay modes. Our present analysis indicates a very rich yield of over 200K reconstructed charm decays.Comment: 4 pages, 1 figure, LaTe

Rev-erbα in the brain is essential for circadian food entrainment.

Foraging is costly in terms of time and energy. An endogenous food-entrainable system allows anticipation of predictable changes of food resources in nature. Yet the molecular mechanism that controls food anticipation in mammals remains elusive. Here we report that deletion of the clock component Rev-erbα impairs food entrainment in mice. Rev-erbα global knockout (GKO) mice subjected to restricted feeding showed reduced elevations of locomotor activity and body temperature prior to mealtime, regardless of the lighting conditions. The failure to properly anticipate food arrival was accompanied by a lack of phase-adjustment to mealtime of the clock protein PERIOD2 in the cerebellum, and by diminished expression of phosphorylated ERK 1/2 (p-ERK) during mealtime in the mediobasal hypothalamus and cerebellum. Furthermore, brain-specific knockout (BKO) mice for Rev-erbα display a defective suprachiasmatic clock, as evidenced by blunted daily activity under a light-dark cycle, altered free-running rhythm in constant darkness and impaired clock gene expression. Notably, brain deletion of Rev-erbα totally prevented food-anticipatory behaviour and thermogenesis. In response to restricted feeding, brain deletion of Rev-erbα impaired changes in clock gene expression in the hippocampus and cerebellum, but not in the liver. Our findings indicate that Rev-erbα is required for neural network-based prediction of food availability.journal article2016 Jul 062016 07 06importe

Inhibition promotes long-term potentiation at cerebellar excitatory synapses.

The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses.journal article2016 Sep 192016 09 19importe

Enhancing implementation of tobacco use prevention and cessation counselling guideline among dental providers: a cluster randomised controlled trial

Background: Tobacco use adversely affects oral health. Tobacco use prevention and cessation (TUPAC) counselling guidelines recommend that healthcare providers ask about each patient's tobacco use, assess the patient's readiness and willingness to stop, document tobacco use habits, advise the patient to stop, assist and help in quitting, and arrange monitoring of progress at follow-up appointments. Adherence to such guidelines, especially among dental providers, is poor. To improve guideline implementation, it is essential to understand factors influencing it and find effective ways to influence those factors. The aim of the present study protocol is to introduce a theory-based approach to diagnose implementation difficulties of TUPAC counselling guidelines among dental providers.Methods: Theories of behaviour change have been used to identify key theoretical domains relevant to the behaviours of healthcare providers involved in implementing clinical guidelines. These theoretical domains will inform the development of a questionnaire aimed at assessing the implementation of the TUPAC counselling guidelines among Finnish municipal dental providers. Specific items will be drawn from the guidelines and the literature on TUPAC studies. After identifying potential implementation difficulties, we will design two interventions using theories of behaviour change to link them with relevant behaviour change techniques aiming to improve guideline adherence. For assessing the implementation of TUPAC guidelines, the electronic dental record audit and self-reported questionnaires will be used.Discussion: To improve guideline adherence, the theoretical-domains approach could provide a comprehensive basis for assessing implementation difficulties, as well as designing and evaluating interventions. After having identified implementation difficulties, we will design and test two interventions to enhance TUPAC guideline adherence. Using the cluster randomised controlled design, we aim to provide further evidence on intervention effects, as well as on the validity and feasibility of the theoretical-domain approach. The empirical data collected within this trial will be useful in testing whether this theoretical-domain approach can improve our understanding of the implementation of TUPAC guidelines among dental providers

Mindfulness-Based Stress Reduction in Women with Overweight or Obesity: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the feasibility and cardiometabolic effects of mindfulness-based stress reduction (MBSR) in women with overweight or obesity. METHODS: Eighty-six women with BMI ≥ 25 kg/m RESULTS: Compared to health education, the MBSR group demonstrated significantly improved mindfulness at 8 weeks (mean change from baseline, 4.5 vs. -1.0; P = 0.03) and significantly decreased perceived stress at 16 weeks (-3.6 vs. -1.3, P = 0.01). In the MBSR group, there were significant reductions in fasting glucose at 8 weeks (-8.9 mg/dL, P = 0.02) and at 16 weeks (-9.3 mg/dL, P = 0.02) compared to baseline. Fasting glucose did not significantly improve in the health education group. There were no significant changes in blood pressure, weight, or insulin resistance in the MBSR group. CONCLUSIONS: In women with overweight or obesity, MBSR significantly reduces stress and may have beneficial effects on glucose. Future studies demonstrating long-term cardiometabolic benefits of MBSR will be key for establishing MBSR as an effective tool in the management of obesity