Effect of permafrost thawing on organic carbon and trace element colloidal speciation in the thermokarst lakes of western Siberia

To examine the mechanisms of carbon mobilization and biodegradation during permafrost thawing and to establish a link between organic carbon (OC) and other chemical and microbiological parameters in forming thermokarst (thaw) lakes, we studied the biogeochemistry of OC and trace elements (TEs) in a chronosequence of small lakes that are being formed due to permafrost thawing in the northern part of western Siberia. Twenty lakes and small ponds of various sizes and ages were sampled for dissolved and colloidal organic carbon, metals and culturable heterotrophic bacterial cell number. We observed a sequence of ecosystems from peat thawing and palsa degradation due to permafrost subsidence in small ponds to large, km-size lakes that are subject to drainage to, finally, the khasyrey (drained lake) formation. There is a systematic evolution of both total dissolved and colloidal concentration of OC and TEs in the lake water along with the chronosequence of lake development that may be directly linked to the microbial mineralization of dissolved organic matter and the liberation of the inorganic components (Fe, Al, and TEs) from the organo-mineral colloids. <br><br> In this chronosequence of lake development, we observed an apparent decrease in the relative proportion of low molecular weight <1 kDa (1 kDa ~ 1 nm) OC concentration along with a decrease in the concentration of total dissolved (<0.45 μm) OC. This decrease was accompanied by an increase in the small size organic ligands (probably autochthonous exometabolites produced by the phytoplankton) and a simultaneous decrease in the proportion of large-size organic (humic) complexes of allochthonous (soil) origin. This evolution may be due to the activity of heterotrophic bacterioplankton that use allochthonous organic matter and dissolved nutrients originating from peat lixiviation. Most insoluble TEs demonstrate a systematic decrease in concentration during filtration (5 μm, 0.45 μm) exhibiting a similar pattern among different samples. At the same time, there is an increase in the relative proportion of large size particles over the <1 kDa fraction for most insoluble elements along the chronosequence of lake evolution. TEs are likely to be bound to colloidal OC and coprecipitate with the mineral (Fe, Al) part of the colloids. Upon progressive consumption of dissolved OC by the heterotrophic bacteria, there is liberation of Fe, Al, and insoluble TEs in the water column that may be subjected to coagulation in the form of particles or large-size mineral colloids

The National Pediatric Surgery Simulation Program in France: A tool to develop resident training in pediatric surgery

BACKGROUND/PURPOSE: To implement resident curriculum in France based on theoretical teaching and bed side training, the national council known as the "Collège Hospitalier et Universitaire de Chirurgie Pédiatrique" examined the relevance and feasibility of systematically introducing simulation program in the pediatric surgery resident training. MATERIAL AND METHODS: A national simulation training program was developed and took place in a 2-day session organized in 7 simulation centers in France. The program included technical (laparoscopic/suturing technique on low-fidelity models) and nontechnical (6 scenarios for standardized consultation, and a team work scenario based on errors prevention in the operative room) skills. Evaluation of the program (Likert scale from 1 (bad) to 5 (excellent) and notation on 20 points) concerned trainees and trainers. RESULTS: 40 residents (95% of all pediatric surgery French residents) attended with a ratio of trainees/trainer of ½. The training objectives earned a score of 4.46/5. The pedagogical value of the seminar scored 4.7/5, teaching quality 17.95/20, and the overall seminar score was 17.35/20. CONCLUSION: This program, unique nationally, was assessed very favorably by the participating residents and by the involved trainers. To our knowledge, it represents the first mandatory national simulation training program included within a surgical training model. LEVEL OF EVIDENCE: Level IV

The inhibition of checkpoint activation by telomeres does not involve exclusion of dimethylation of histone H4 lysine 20 (H4K20me2) [version 2; referees: 2 approved, 1 not approved]

DNA double-strand breaks (DSBs) activate the DNA damage checkpoint machinery to pause or halt the cell cycle.  Telomeres, the specific DNA-protein complexes at linear eukaryotic chromosome ends, are capped DSBs that do not activate DNA damage checkpoints.  This “checkpoint privileged” status of telomeres was previously investigated in the yeast Schizosaccharomyces pombelacking the major double-stranded telomere DNA binding protein Taz1. Telomeric DNA repeats in cells lacking Taz1 are 10 times longer than normal and contain single-stranded DNA regions. DNA damage checkpoint proteins associate with these damaged telomeres, but the DNA damage checkpoint is not activated. This severing of the DNA damage checkpoint signaling pathway was reported to stem from exclusion of histone H4 lysine 20 dimethylation (H4K20me2) from telomeric nucleosomes in both wild type cells and cells lacking Taz1.  However, experiments to identify the mechanism of this exclusion failed, prompting our re-evaluation of H4K20me2 levels at telomeric chromatin.  In this short report, we used an extensive series of controls to identify an antibody specific for the H4K20me2 modification and show that the level of this modification is the same at telomeres and internal loci in both wild type cells and those lacking Taz1.  Consequently, telomeres must block activation of the DNA Damage Response by another mechanism that remains to be determined

Der Verbleib kupferbasierter Fungizide in Weinbergböden: Eine Fallstudie der stabilen Kupfer-Isotopenverhältnisse und Elektronenspinresonanz von Calco- und Vertisolen in Soave (Italien)

Kupferbasierte Fungizide sind im Weinbau weit verbreitet und im biologischen Weinbau die einzig erlaubten Pestizide zur Bekämpfung von falschem Mehltau. Durch den intensiven, dauerhaften Gebrauch von Kupfer reichert sich dieser, mit wachsenden ökotoxikologischen Konsequenzen, in Weinbergböden an. In dieser Studie untersuchen wir den Verbleib von Kupfer in einem Calcosol und einem Vertisol aus Soave (Italien). Beide Böden werden seit über 50 Jahren mit Kupfer behandelt. Wir stellen Massenbilanzen auf und nutzen die innovative Kombination aus Messung stabiler Cu-Isotopenverhältnisse und Elektronenspinresonanzspektroskopie (ESR), um Einblicke in die biogeochemischen Mechanismen der Kupferbindung zu erlangen. Die untersuchten Böden weisen hohe exogene Kupfergehalte auf, welche eine Akkumulation der heutigen maximalen Behandlungsmenge über 50 Jahre überschreiten. Dies belegt, dass einmal sehr viel größere Mengen Cu im Weinbau verwendet wurden und dass ein Großteil dieses Kupfers in den jeweiligen Böden verbleibt. In Vertisolen fallen die Cu-Konzentrationen unter dem vertischen Horizont schnell auf die geogene Hintergrundkonzentration, wobei in Calcosolen dieser Abfall progressiver erfolgt. Isotopenverhältnisse unterscheiden sich zwischen den verschieden Bodentypen (δCu-65 zwischen 0.12 und 0.37 ‰), obwohl sie die gleiche Behandlung erfahren haben. Kupferisotope in Oberböden sind schwerer als in Unterböden und Citratextraktionen zeigen, dass mobiles Kupfer isotopisch schwerer ist als der Gesamtgehalt. Die Horizonte des Calcosols sind systematisch leichter als die des Vertisols, was auf unterschiedliche biogeochemische Bindungsmechanismen von Kupfer hinweist. Dies wird durch die ESR-Spektren bestätigt. In Oberböden zeigen sie eine Kupferbindung an organisches Material, wobei es im gesamten Bodenprofil Unterschiede in der Cu-Bindung zwischen den beiden Bodentypen gibt. Wenn jedoch Horizonte des Calcosols mit Säure entkalkt werden, nähren sich deren ESR-Spektren denen der Vertisole an, wohingegen letztere nicht auf eine Säurebehandlung reagieren. Somit wird gezeigt, dass in Calcosolen Karbonate an der Bindung von Kupfer beteiligt sind wobei in Vertisolen der vertische Horizont eine wichtige Rolle spielt. Darüber hinaus wird durch die analoge Variation von ESR-Spektren und Isotopenverhältnissen wird die Anwendbarkeit von Cu-Isotopenanalysen und ESR-Spektroskopie zur Aufklärung von biogeochemischen Prozessen in Böden demonstriert

Transcription-replication conflicts: How they occur and how they are resolved

The frequent occurrence of transcription and DNA replication in cells results in many encounters, and thus conflicts, between the transcription and replication machineries. These conflicts constitute a major intrinsic source of genome instability, which is a hallmark of cancer cells. How the replication machinery progresses along a DNA molecule occupied by an RNA polymerase is an old question. Here we review recent data on the biological relevance of transcription-replication conflicts, and the factors and mechanisms that are involved in either preventing or resolving them, mainly in eukaryotes. On the basis of these data, we provide our current view of how transcription can generate obstacles to replication, including torsional stress and non-B DNA structures, and of the different cellular processes that have evolved to solve them

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Harmful Elements in Estuarine and Coastal Systems

Estuaries and coastal zones are dynamic transitional systems which provide many economic and ecological benefits to humans, but also are an ideal habitat for other organisms as well. These areas are becoming contaminated by various anthropogenic activities due to a quick economic growth and urbanization. This chapter explores the sources, chemical speciation, sediment accumulation and removal mechanisms of the harmful elements in estuarine and coastal seawaters. It also describes the effects of toxic elements on aquatic flora and fauna. Finally, the toxic element pollution of the Venice Lagoon, a transitional water body located in the northeastern part of Italy, is discussed as a case study, by presenting the procedures adopted to measure the extent of the pollution, the impacts on organisms and the restoration activities

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570