Biochemical properties of Paracoccus denitrificans FnrP:Reactions with molecular oxygen and nitric oxide

In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster containing homologue of the archetypal O2 sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O2, and also NO, availability. Here we show that FnrP undergoes O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O2 per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O2 concentrations. The rate of the cluster reaction was found to be ~6-fold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O2 affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

The restorative role of annexin A1 at the blood–brain barrier

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood–brain barrier damage in disease and aging

Changes in Ureteral Stone Treatment During COVID-19: A Single-Center Emergency Department Study

Adrian Militaru,1,2 Catalin Andrei Bulai,1,2 Cosmin Victor Ene,1,2 Razvan Ionut Popescu,1,3 Cristian Mares,1,2 Stefan Marian Balacescu,1,2 Razvan Dragos Multescu,1,2 Dragos Adrian Georgescu,1,2 Petrisor Aurelian Geavlete,1,2 Bogdan Florin Geavlete1,2 1Department of Urology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; 2Department of Urology, “Saint John” Clinical Emergency Hospital, Bucharest, Romania; 3Department of Urology, “Prof. Dr. Th. Burghele” Clinical Hospital, Bucharest, RomaniaCorrespondence: Catalin Andrei Bulai, Department of Urology, “Saint John” Clinical Emergency Hospital, 13 Vitan-Barzesti str, Bucharest, 042122, Romania, Tel +40749184205, Email [email protected]: We evaluated the hospitalization rate, length of stay, and management of patients with ureteric lithiasis admitted under emergency conditions at a single institution during the COVID-19 pandemic.Patients and Methods: A retrospective study was conducted on 219 patients with ureteral lithiasis, divided into pre-COVID-19 (1.10.2019– 29.02.2020) and COVID-19 groups (1.10.2020– 29.02.2021). The study examined patient and stone characteristics, hospitalization duration, surgical interventions, creatinine levels, and associated urinary tract infections. It also evaluated the complications related to delayed treatment during the pandemic.Results: The study found a 73.41% reduction in admissions for obstructive ureteral lithiasis during the COVID-19 pandemic compared to the pre-pandemic period. Notable differences were observed in age (61.5 vs 46 years, p=0.000), gender (p=0.046), stone laterality (p=0.024), location (p=0.002), serum creatinine levels (1.59 vs 1.09 mg/dL, p=0.000), and urine cultures (45.65% vs 23.12%, p=0.002). During the pandemic period, the rate of primary stone extraction procedures decreased (32.6% vs 59%, p< 0.001), while operative time (52.89 vs 39.84 minutes, p< 0.001) and hospital stay significantly increased (13.09 vs 3.76 days, p< 0.001).Conclusion: The pandemic resulted in fewer hospitalizations for ureteral lithiasis and an increase in complications, likely due to reduced access to medical care and a greater tendency for upper urinary tract drainage.Keywords: COVID-19, urolithiasis, ureteroscopy, double J stent, ureteral stone, percutaneous nephrostom

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Identification and Filtering of Uncharacteristic Noise in the CMS Hadron Calorimeter

VertaisarvioitupeerReviewe

Performance of CMS hadron calorimeter timing and synchronization using test beam, cosmic ray, and LHC beam data

This paper discusses the design and performance of the time measurement technique and of the synchronization systems of the CMS hadron calorimeter. Time measurement performance results are presented from test beam data taken in the years 2004 and 2006. For hadronic showers of energy greater than 100 GeV, the timing resolution is measured to be about 1.2 ns. Time synchronization and out-of-time background rejection results are presented from the Cosmic Run At Four Tesla and LHC beam runs taken in the Autumn of 2008. The inter-channel synchronization is measured to be within ±2 ns

Defective Interfering Viral Particles in Acute Dengue Infections

While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3′ and 5′ ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6–36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses

Search for supersymmetry in pp collisions at 7 TeV in events with jets and missing transverse energy

A search for supersymmetry with R-parity conservation in proton-proton collisions at a centre-of-mass energy of 7 TeV is presented. The data correspond to an integrated luminosity of 35 pb(-1) collected by the CMS experiment at the LHC. The search is performed in events with jets and significant missing transverse energy, characteristic of the decays of heavy, pair-produced squarks and gluinos. The primary background, from standard model multijet production, is reduced by several orders of magnitude to a negligible level by the application of a set of robust kinematic requirements. With this selection, the data are consistent with the standard model backgrounds, namely t (t) over bar, W + jet and Z + jet production, which are estimated from data control samples. Limits are set on the parameters of the constrained minimal supersymmetric extension of the standard model. These limits extend those set previously by experiments at the Tevatron and LEP colliders. (C) 2011 CMS Collaboration