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This study set out to examine pre-analytical factors affecting the frequency of positive results in newborn screening for biotinidase deficiency. This investigation was prompted by an increase in the annual screen positive rate for biotinidase deficiency in Ontario from 2.65x10

This article shares the exciting discovery of previously unidentified arias within the music amassed by the eighteenth-century English poet Thomas Gray. His ten-volume collection, now held at the Lewis Walpole Library, Yale University, contains some of the only surviving copies of important arias dating back as far as 1690 and bears many annotations by Gray listing performance venues, composers, opera roles and singers. One volume of the collection contains many unattributed works, among which I identify a number of arias. Five of them match the libretto to La caduta del regno dell'Amazzoni (1690) and another corresponds to Il Colombo overo l'India scoperta (1691), both operas originally set by Bernardo Pasquini. The texts of the two ensuing arias align with Carlo Sigismondo Capeci's libretto for Ifigenia in Tauri (1713), the opera he wrote with Domenico Scarlatti for their patroness, Maria Kazimiera Sobieska. In addition, in the first pages of the assemblage, instructions in Gray's hand on how to execute a basso-continuo accompaniment continue from another volume, where he entitled these ‘Regole per l'Accompagnamento’ and interwove them with a ‘Toccata per il Cembalo’. This article seeks to describe the newfound works and stimulate study into the full contents of Gray's music collection, but its main focus is on the two excerpts from Ifigenia in Tauri and their possible attribution to Domenico Scarlatti. Salient characteristics of these scores are presented, as is an evaluation of their concordance with Capeci's libretto. Further, I underline features that these numbers share with other Ifigenia in Tauri arias known to be by Domenico Scarlatti and provide comprehensive tables detailing equivalent structural proportions.

Expression of Glu-tRNA and its synthetase from lanthipeptide encoding bacteria using pEVOL improves production in E. coli. Often-observed glutathionylation can be reversed using LanCL enzymes.

Haiti introduced a monovalent human group A rotavirus (RVA) vaccine (Rotarix) into its routine infant immunization program in April 2014. The goal of the surveillance program was to characterize RVA strains circulating in Haiti before and after RVA vaccine introduction.Stool samples were collected from children5 years old presenting with acute gastroenteritis at 16 hospitals in Haiti. RVA antigen enzyme immunoassay (EIA) testing was performed, and G and P genotypes were determined for positive specimens. In this study, genotype data for samples collected from May 2012 through April 2014 (the pre-vaccine introduction era) and May 2014 through July 2019 (post-vaccine introduction era) were analyzed.A total of 809 specimens were tested by the Centers for Disease Control and Prevention. During the pre-vaccine introduction era (May 2012 through April 2014), G12P[8] was the predominant genotype, detected in 88-94% of specimens. There was a high prevalence of the equine-like G3P[8] genotype among Haitian children with RVA after vaccine introduction.The predominance of equine-like G3P[8] in three of five RVA seasons post-vaccine introduction suggests possible vaccine-specific selection pressure in Haiti. These temporal variations in RVA genotype predominance will require continued monitoring in Haiti as the vaccination program continues.

Geomorphologists classically compute denudation rates from in situ cosmogenic 10Be concentrations. A major assumption is that denudation rates remain steady during the 10Be integration time scale. But early 14C-10Be data we presented last year at this conference suggested that this is hardly tested in environments slowly deformed by tectonics, with integration time covering thousands of years, and erosion rates from 10 to 100 mm/ky.Here, we extended our 14C-10Be dataset to test recent and substantial shifts in denudation. 14C is more sensitive than 10Be to recent and short-term changes in denudation, because of a shorter half-life (5,700 y versus 1.4 My). Studies (Hippe, 2017; Mudd, 2017; Skov et al., 2019; Hippe et al., 2021) have discussed this application of coupled 14C - 10Be measurements.We carried out in situ 14C measurements on river sand which has available 10Be date (Desormeaux et Al., 2021). The studied mountain range is called Massif Central and is west of the European Alp foreland, in southern France. Elevation is ~700 m on average, with an elevated low-relief surface and a steep escarpment along the Cevennes Fault bordering the Alp foreland. The area has a homogeneous lithology rich in quartz. Past glaciations were of limited extent. There is little space for sediment storage, thin soils, no dams, and presently limited anthropic activity. Massif Central is only impacted by slow tectonic deformation. Landslides are very rare but erosion processes are active.Our new 14C results combined with Desormeaux et al., 2021's 10Be data confirm the substantial 14C-10Be disequilibrium. 14C apparent denudation rates are several times higher than 10Be denudation rates. We explore four end-members which could explain such a disequilibrium. This exploration suggests that only major and recent events in denudation could produce such a disequilibrium, and that the landscape we presently see is rather transient than steady.

Independent supplementation with nitrate (NIT) and resveratrol (RSV) enriches various aspects of mitochondrial biology in key metabolic tissues. Although RSV is known to activate Sirt1 and initiate mitochondrial biogenesis, the metabolic benefits elicited by dietary nitrate appear to be dependent on 5′-adenosine monophosphate-activated protein kinase (AMPK)-mediated signaling events, a process also linked to the activation of Sirt1. Although the benefits of individual supplementation with these compounds have been characterized, it is unknown if co-supplementation may produce superior metabolic adaptations. Thus, we aimed to determine if treatment with combined +NIT and +RSV (+RN) could additively alter metabolic adaptations in the presence of a high-fat diet (HFD). Both +RSV and +NIT improved glucose tolerance compared with HFD ( P < 0.05); however, this response was attenuated following combined +RN supplementation. Within skeletal muscle, all supplements increased mitochondrial ADP sensitivity compared with HFD ( P < 0.05), without altering mitochondrial content. Although +RSV and +NIT decreased hepatic lipid deposition compared with HFD ( P < 0.05), this effect was abolished with +RN, which aligned with significant reductions in Sirt1 protein content ( P < 0.05) after combined treatment, in the absence of changes to mitochondrial content or function. Within epididymal white adipose tissue (eWAT), all supplements reduced crown-like structure accumulation compared with HFD ( P < 0.0001) and mitochondrial reactive oxygen species (ROS) emission ( P < 0.05), alongside reduced adipocyte cross-sectional area (CSA) ( P < 0.05), with the greatest effect observed after +RN treatment ( P = 0.0001). Although the present data suggest additive changes in adipose tissue metabolism after +RN treatment, concomitant impairments in hepatic lipid homeostasis appear to prevent improvements in whole body glucose homeostasis observed with independent treatment, which may be Sirt1 dependent.

We utilize molecular dynamic simulation to demonstrate that the substrate core peptide sequence plays an important role in controlling the site-selectivity of lanthipeptides.

The French West Indies are made up of the islands of Martinique, Saint-Barthélemy, the northern part of the island of Saint-Martin and the Guadeloupe Archipelago. Through the vocabulary of the Native Americans who lived in this region, it is possible to bring out their finesse of analysis to describe different intensity gradients concerning natural hazards. The research has identified that all natural hazards are mentioned except the volcanic eruptions that were very frequent. From the discussion of the concepts of cultural resilience and culture of resilience, we conclude that this society certainly had a perception of volcanoes with a different time scale than ours, adapted to the impact of hazards and their real threats for their way of life.

Rotavirus is responsible for 26% of diarrheal deaths in Latin America and the Caribbean. Haiti introduced the monovalent rotavirus vaccine in April 2014. The objective of this analysis is to describe the impact of the rotavirus vaccine on hospitalizations among Haitian children younger than 5 years old during the first 5 years after introduction. This analysis includes all children with diarrhea who were enrolled as part of a sentinel surveillance system at two hospitals from May 2013 to April 2019. We compare the proportion of rotavirus-positive specimens in each post-vaccine introduction year to the pre-vaccine period. To account for the potential dilution of the proportion of rotavirus-positive specimens from a waning cholera outbreak, we also analyzed annual trends in the absolute number of positive stools, fit a two-component finite-mixture model to the negative specimens, and fit a negative binomial time series model to the pre-vaccine rotavirus-positive specimens to predict the number of rotavirus diarrhea hospital admissions in the absence of rotavirus vaccination. The overall percentage of rotavirus-positive specimens declined by 22% the first year after introduction, increased by 17% the second year, and declined by 33% to 50% the subsequent 3 years. All sensitivity analyses confirmed an overall decline. We observed a clear annual rotavirus seasonality before and after vaccine introduction, with the greatest activity in December through April, and a biennial pattern, with high sharp peaks and flatter longer periods of increased rotavirus activity in alternating years, consistent with suboptimal vaccination coverage. Overall, our study shows evidence that the introduction of the rotavirus vaccine reduced the burden of severe rotavirus diarrhea.

Lanthipeptides are ribosomally synthesized and post-translationally modified peptides that are generated from precursor peptides through a dehydration and cyclization process in the biosynthetic pathways. In contrast to most other lanthipeptide synthetases, ProcM, a class II lanthipeptide synthetase, demonstrates high substrate tolerance. It is enigmatic that a single enzyme can catalyze the cyclization process of a diverse range of substrates with high fidelity. Previous studies suggested that the site-selectivity of lanthionine formation is determined by substrate sequence rather than by the enzyme. However, exactly how substrate sequence contributes to site-selective lanthipeptide biosynthesis is not clear. In this study, we performed molecular dynamic simulations for ProcA3.3 core peptide variants to explore how the predicted solution structure of the substrate without enzyme correlates to final product formation. Our simulation results support a model in which the secondary structure of the core peptide controls the ring pattern of the final product. We also demonstrate that the dehydration step in the biosynthesis pathway does not influence the site-selectivity of ring formation. In addition, we performed simulation for the core peptides of ProcA1.1 and 2.8, which are well-suited candidates to investigate the connection between order of ring formation and solution structure. Simulation results indicate that in both cases, C-terminal ring formation is more likely which was supported by experimental results. Our findings indicate that the substrate sequence and its solution structure can be used to predict the site-selectivity and order of ring formation, and that secondary structure is a crucial factor influencing the site-selectivity. Taken together, these findings will facilitate our understanding of the lanthipeptide biosynthetic mechanism and accelerate bioengineering efforts for lanthipeptide-derived products.

Introduction: Latino parents have significant knowledge gaps and misconceptions about fever. In this study, we explored Latino beliefs and practices around fever and its impact on their care decisions. Methods: A qualitative-focused ethnography was conducted with 21 Latino parents. Semi-structured interviews were completed, and inductive thematic analysis was used to identify themes and subthemes. Results: Three major themes emerged: (a) the meaning of fever; (b) seeking guidance; and (c) navigating fever. Subthemes included: a sign of folk illness, a sign of infection, trust in health care providers, watchful waiting, and barriers and needs. Discussion: Latino parents have significant knowledge gaps about the role of fever in illness. They engage multiple systems of care but rarely share their fears with health care providers. Culturally-sensitive interventions incorporating traditional and biomedical approaches are needed. Findings can help inform future interventions targeting knowledge gaps in this population.

The transport of long chain fatty acids (LCFA) and adenosine diphosphate (ADP) across the inner mitochondrial membrane are two major control points which influence the rate of oxidative phosphorylation. Although very little is known of the regulation of substrate transport/delivery, the recent discovery of a specific pool of 5’AMP kinase (AMPK) bound to the mitochondria presents as an attractive avenue. Herein, acute activation of AMPK by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) increases mitochondrial ADP sensitivity and L-Carnitine sensitivity independent of changes in maximal respiratory capacity. Additionally, mice fasted for 24h displayed a strong trend for increased AMPK phosphorylation (p=0.075) but had a decrease in ADP sensitivity in the absence of changes in maximal oxidative phosphorylation. While both models resulted in increased AMPK phosphorylation, the diverging response on ADP sensitivity could be due to the activation of different subcellular AMPK pools, where AICAR increases mitochondrial AMPK phosphorylation, but fasting does not. 2023-08-04

La promesse d’un « réel » incrédible fait partie du champ du récit considéré comme une marchandise ; cela hausse le « prix » du récit [...] Roland Barthes, L’Aventure sémiologique, 1985, p. 347 ou Œuvres complètes, p. 431. Dès 1844, au moment de la publication de Jeanne, qu’elle considère comme son premier roman-feuilleton, George Sand embrasse son nouveau métier, sinon à contrecœur, du moins avec réticence. Romancière têtue et sûre de ses moyens, elle reconnaît pourtant ses limites face à de...

On ignore encore souvent que George Sand a été une journaliste prolixe tout au long de sa vie. Polygraphe, elle ne s’est pas cantonnée à une forme ou une rubrique mais elle a utilisé toute la palette du journaliste et du reviewer : elle a pratiqué la critique dramatique, la critique littéraire, la critique picturale, les grands articles politiques, le récit de voyage, les études de mœurs, les nécrologies, le billet d’humeur, le droit de réponse. Elle a fréquenté tous les types possibles de journaux : quotidiens, grandes revues, magazines, illustrés, petits journaux littéraires... Elle-même ne considérait pas cette production comme mineure dans l’ensemble de son œuvre puisque régulièrement elle s’est évertuée à faire publier en recueils ses articles. Cet ouvrage se propose d’étudier les relations de George Sand avec la presse notamment dans l’édification d’une pensée du média, ce qu’elle-même appelait « la science du journalisme », avec ses crises et ses aléas. Mais ce volume montre aussi que si George Sand est réceptive aux mutations d’une écriture journalistique en plein bouleversement, elle fait aussi du journal très explicitement son propre œuvre en détournant tous les codes attendus pour produire des textes hors norme. Cette expérience de la presse irrigue le reste de son œuvre, du roman-feuilleton à l’œuvre autobiographique en passant par le théâtre.

A self-complementary graph is a graph isomorphic to its complement. A set S of vertices in a graph G is a restrained dominating set if every vertex in V(G) \ S is adjacent to a vertex in S and to a vertex in V(G) \ S. The restrained domination number of a graph G is the minimum cardinality of a restrained dominating set of G. In this paper, we study restrained domination in self-complementary graphs. In particular, we characterize the self-complementary graphs having equal domination and restrained domination numbers.

The aim of this study was to provide a baseline assessment of the turtle community in the coastal wetlands of the Greater Toronto Area. We documented turtle species diversity, abundance, reproductive classes, sex-ratios, and evidence of inter-wetland movement. Our study consisted of a series of mark-recapture surveys across eleven Lake Ontario coastal wetland complexes of the Greater Toronto Area performed between 2016 and 2019. We captured and marked 532 individual turtles of four native species (298 midland painted, Chrysemys picta marginata; 180 snapping, Chelydra serpentina; 7 Blanding’s, Emydoidea blandingii, and 5 map, Graptemys geographica) and three non-native species (40 red-eared slider, Trachemys scripta elegans; 1 false map, Graptemys pseudogeographica, and 1 Chinese softshell, Pelodiscus sinensis). Of note was the capture of an exceptionally large male snapping turtle, one of the largest recorded in Canada for both length and mass. The age classes of both snapping and midland painted species presented large proportions of breeding-sized adults, yet midland painted turtles showed a potential low recruitment with an underrepresentation of non-reproductive females. The sex ratios of both midland painted and snapping turtles across the whole waterfront did not differ from the expected 1:1 ratio. We also recaptured 198 turtles (135 midland painted, 53 snapping, 6 Blanding’s and 12 red-eared Sliders). The recaptured turtles revealed inter-wetland movements of 12 km over a two-year span for a midland painted turtle and an 8 km journey for a snapping turtle, potentially demonstrating some connectivity between geographically separate wetland complexes.

Casein Kinase 2 (CSNK2) is an extremely pleiotropic, ubiquitously expressed protein kinase involved in the regulation of numerous key biological processes. Mapping the CSNK2-dependent phosphoproteome is necessary for better characterization of its fundamental role in cellular signalling. While ATP-competitive inhibitors have enabled the identification of many putative kinase substrates, compounds targeting the highly conserved ATP-binding pocket often exhibit off-target effects limiting their utility for definitive kinase-substrate assignment. To overcome this limitation, we devised a strategy combining chemical genetics and quantitative phosphoproteomics to identify and validate CSNK2 substrates. We engineered U2OS cells expressing exogenous wild type CSNK2A1 (WT) or a triple mutant (TM, V66A/H160D/I174A) with substitutions at residues important for inhibitor binding. These cells were treated with CX-4945, a clinical-stage inhibitor of CSNK2, and analyzed using large-scale triple SILAC (Stable Isotope Labelling of Amino Acids in Cell Culture) quantitative phosphoproteomics. In contrast to wild-type CSNK2A1, CSNK2A1-TM retained activity in the presence of CX-4945 enabling identification and validation of several CSNK2 substrates on the basis of their increased phosphorylation in cells expressing CSNK2A1-TM. Based on high conservation within the kinase family, we expect that this strategy can be broadly adapted for identification of other kinase-substrate relationships.

Exotic species are often vilified as “bad” without consideration of the potential they have for contributing to ecological functions in degraded ecosystems. The red-eared slider turtle (RES) has been disparaged as one of the worst invasive species. Based on this review, we suggest that RES contribute some ecosystem functions in urban wetlands comparable to those provided by the native turtles they sometimes dominate or replace. While we do not advocate for releases outside their native range, or into natural environments, in this review, we examine the case for the RES to be considered potentially beneficial in heavily human-altered and degraded ecosystems where native turtles struggle or fail to persist. After reviewing the ecosystem functions RESs are known to provide, we conclude that in many modified environments the RES is a partial ecological analog to native turtles and removing them may obviate the ecological benefits they provide. We also suggest research avenues to better understand the role of RESs in heavily modified wetlands.

Between 2011 and 2020, the Ontario Turtle Conservation Centre's veterinary hospital admitted 6,335 turtles of eight different species, with 3,246 being midland painted turtles (Chrysemys picta marginata). At the time of admission from the wild, aural abscesses were present in 26 of the painted turtles (0.8%). Aural abscesses were never observed in juvenile turtles and were not found in any other species of turtle admitted to the hospital. An equal number of males and females were affected. All cases showed signs of chronicity. Abscesses alone did not appear to affect the overall health of turtles regardless of clinical signs. All turtles with abscesses as the sole cause for admission were released after successful treatment.

Active faults play a major role in relief building, partly through the accumulation of vertical co seismic displacement during major earthquakes. Triangular facets are geomorphic features recording normal fault cumulative displacements on relatively long time scales (10-100ka). To unravel the relationships between the rate at which slip accumulates on a fault scarp and the long-term evolution of triangular facets, we have to acquire quantitative datasets on normal fault slip rates at various timescales and rates of erosion of the facets.Here we present a study on facet build-up over 10-100 ka time range in the central Apennines in Italy. The normal fault systems that control the present tectonic activity of the range are very well studied with numerous detailed paleoseismological records. We focus on the Magnola-Velino fault system which displays well preserved triangular facets and accurate chronological constraints on the 10-20m high fault scarp located at the base of the facets. We combine high resolution morphometric analysis (gullies steepness, facets slope and others), using Digital Elevation Models derived from Pléiades imagery and a new dataset for cosmogenic nuclides concentration (36Cl) including 54 bedrock samples on 9 gullies and facets profiles above the scarps. Magnola-Velino fault system is 20-25km long, and morphometric parameters such as steepness index display a systematic evolution along strike. First measured 36Cl concentrations, on Magnola, range from 6 to 50 x104 at/g on gullies and 50 to 150 x104 at/g on facets, with systematic variations along strike. We document the joint evolution of geochronological data and morphological parameters for this fault system and compare it with existing constraints on long-term slip rate.

Within brown adipose tissue (BAT), the brain isoform of creatine kinase (CKB) has been proposed to regulate the regeneration of ADP and phosphocreatine in a futile creatine cycle (FCC) that stimulates energy expenditure. However, the presence of FCC, and the specific creatine kinase isoforms regulating this theoretical model within white adipose tissue (WAT), remains to be fully elucidated. In the present study, creatine did not stimulate respiration in cultured adipocytes, isolated mitochondria or mouse permeabilized WAT. Additionally, while creatine kinase ubiquitous-type, mitochondrial (CKMT1) mRNA and protein were detected in human WAT, shRNA-mediated reductions in Ckmt1 did not decrease submaximal respiration in cultured adipocytes, and ablation of CKMT1 in mice did not alter energy expenditure, mitochondrial responses to pharmacological β3-adrenergic activation (CL 316, 243) or exacerbate the detrimental metabolic effects of consuming a high-fat diet. Taken together, these findings solidify CKMT1 as dispensable in the regulation of energy expenditure, and unlike in BAT, they do not support the presence of FCC within WAT.

This study evaluated the water quality produced by forward osmosis-reverse osmosis (FO-RO) treatment at pilot scale of RO concentrate generated at centralized potable reuse facilities and of graywa...

Cruzain, an essential cysteine protease of the parasitic protozoan, Trypanosoma cruzi, is an important drug target for Chagas disease. We describe here a new series of reversible but time-dependent inhibitors of cruzain, composed of a dipeptide scaffold appended to vinyl heterocycles meant to provide replacements for the irreversible reactive “warheads” of vinyl sulfone inactivators of cruzain. Peptidomimetic vinyl heterocyclic inhibitors (PVHIs) containing Cbz-Phe-Phe/homoPhe scaffolds with vinyl-2-pyrimidine, vinyl-2-pyridine, and vinyl-2-(N-methyl)-pyridine groups conferred reversible, time-dependent inhibition of cruzain (K(i)* = 0.1–0.4 μM). These cruzain inhibitors exhibited moderate to excellent selectivity versus human cathepsins B, L, and S and showed no apparent toxicity to human cells but were effective in cell cultures of Trypanosoma brucei brucei (EC(50) = 1–15 μM) and eliminated T. cruzi in infected murine cardiomyoblasts (EC(50) = 5–8 μM). PVHIs represent a new class of cruzain inhibitors that could progress to viable candidate compounds to treat Chagas disease and human sleeping sickness.

OBJECTIVE Data from rigorous evaluations of the impact of interventions on improving surgical antibiotic prophylaxis (SAP) compliance in pediatrics are lacking. Our objective was to assess the impact of a multifaceted intervention on improving pediatric SAP compliance in a hospital without an ongoing antimicrobial stewardship program. STUDY DESIGN A multidisciplinary team at the Montreal Children's Hospital performed a series of interventions designed to improve pediatric SAP compliance in June 2015. A retrospective, quasi-experimental study was performed to assess SAP compliance before and following the interventions. Our study included patients under 18 years old undergoing surgery between April and September in 2013 (preintervention) and in 2016 (postintervention). A 10-week washout period was included to rigorously assess the persistence of compliance without ongoing interventions. SAP, when indicated, was qualified as noncompliant, partially compliant (adequate agent and timing) or totally compliant (adequate agent, dose, timing, readministration, duration). RESULTS A total of 982 surgical cases requiring SAP were included in our primary analysis. The composite partial and total compliance increased from 51.4% to 55.8% [adjusted odds ratio 1.3; 95% confidence interval: 1.0-1.8; P = 0.06]. Although improvements in correct dose and readministration were significant, there was no significant improvement in correct timing, agent selection or duration. CONCLUSION Our study demonstrated that overall SAP compliance did not significantly improve following a washout period, illustrating the importance of ongoing surveillance and feedback from an antimicrobial stewardship program. Our strict approach in evaluating the timing criterion may also explain the lack of a significant impact on SAP compliance.

This book provides a comprehensive overview of the future scenarios of climate change and management concerns associatedwith climate change impacts on the blue economy of European islands and outermost regions. The publication collectsmajor findings of the Soclimpact project’s research outcomes, aiming to raise social awareness among policy-makers andindustry about climate change consequences at local level, and provide knowledge based information in support policy design,from local to national level. This comprehensive book will also assist students, scholars and practitioners to understand,conceptualize and effectively and responsibly manage climate change information and applied research. This book providesinvaluable material for Blue Growth Management, theory and application, at all levels. This first edition includes up-to-datedata, statistics, references, case material and figures of the 12 islands case studies. ¨Downscaling climate change impacts,socio-economic implications and alternative adaptation pathways for Islands and Outermost Regions¨ is a must-read book,given the accessible style and breadth and depth with which the topic is dealt. The book is an up-to-date synthesis of keyknowledge on this area, written by a multidisciplinary group of experts on climate and economic modelling, and policy design.

We report on the results of the first mark–recapture survey of freshwater turtles in an isolated urban wetland complex in one of Canada’s fastest growing municipalities. Although we found turtles in every surveyed wetland, the density and assemblage of turtles in smaller wetlands were significantly different than in larger wetland bodies. We also documented two species of turtles that were thought to be absent from this wetland complex, the Northern Map turtle and Eastern Musk turtle. We noted that a wetland that was bisected by a high-traffic road showed a male-skewed sex ratio in the population of Midland Painted turtles but not in the population of Eastern Snapping turtles. As a whole, the sex ratios inside the wetland complex were not skewed. These results reinforce the conclusions of a previous study of a single wetland within this same complex that had found a correlation between road mortality and a male-skewed sex ratio in Midland painted turtles. We discuss population sources and sinks within the complex and the importance of protecting the overland corridors that support the safe turtle movements within this provincially significant wetland complex.

International audience; Investigating landscapes evolution and their responses to tectonic or climatic perturbation requires accurate representations and models of surfaces processes. Rivers are keys agents of the transmission of external forcing through landscape and the main drivers of continental denudation. For these reasons the mechanisms of fluvial incision have been a key focus of geomorphological research over the last decades.Long-term river incision is usually modeled with the Stream Power Model (Howard et al. 1997; Whipple & Tucker 1999) based on the along-stream evolution of drainage area and channel elevation gradient. More complex development of the SPM (Tucker 2004; Lague et al. 2005) combine instantaneous river incision with the probability for discharge occurrence and take into account incision threshold and discharge variability. These models have been confronted with fields data in a limited number of cases (DiBiase et al. 2011, Scherler et al. 2017, Campforts et al. 2020).Our objective is to investigate the behavior of stochastic-threshold incision models across the south-eastern margin of the Massif Central (France) where a strong gradient in discharge variability is reported. We present a new dataset combining measurements of discharge variability from gauging stations, denudation rates on 34 basins from 10Be cosmogenic nuclides and morphometric parameters from river long-profile analysis.Our results show a complex relationship between denudation rates and steepness index which cannot be explain only by the regional discharge variability gradient. When compared with measured erosion rates, we observe that the predictions of a stochastic-threshold incision model are not better than simpler versions of the SPM and require to take into account spatial variations in incision thresholds.

Assessments of ecosystem service and function losses of wetlandscapes (i.e., wetlands and their hydrological catchments) suffer from knowledge gaps regarding impacts of ongoing hydro-climatic change. This study investigates hydro-climatic changes during 1976–2015 in 25 wetlandscapes distributed across the world’s tropical, arid, temperate and cold climate zones. Results show that the wetlandscapes were subject to precipitation (P) and temperature (T) changes consistent with mean changes over the world’s land area. However, arid and cold wetlandscapes experienced higher T increases than their respective climate zone. Also, average P decreased in arid and cold wetlandscapes, contrarily to P of arid and cold climate zones, suggesting that these wetlandscapes are located in regions of elevated climate pressures. For most wetlandscapes with available runoff (R) data, the decreases were larger in R than in P, which was attributed to aggravation of climate change impacts by enhanced evapotranspiration losses, e.g. caused by land-use changes.

Long-term landscape evolution is controlled by tectonic and climatic forcing acting through surface processes. Rivers are the main drivers of continental denudation because they set the base level of most hillslopes. The mechanisms of fluvial incision are thus a key focus in geomorphological research and require accurate representation and models. River incision is often modeled with a stream power model (SPM) based on the along-stream evolution of drainage area and channel elevation gradient but can also incorporate more complex processes such as threshold effects and statistical discharge distributions, which are fundamental features of river dynamics. Despite their importance in quantitative geomorphology, such model formulations have been confronted with field data only in a limited number of cases. Here we investigate the behavior of stochastic-threshold incision models across the southeastern margin of the French Massif Central, which is characterized by significant relief and the regular occurrence of high-discharge events. Our study is based on a new dataset combining measurements of discharge variability from gauging stations, denudation rates from 34 basins from 10Be cosmogenic radionuclide (CRN) concentration measurements in river sediments, morphometric analysis of river long profiles, and field observations. This new dataset is used for a systematic investigation of various formulations of the SPM and to discuss the importance of incision thresholds. Denudation rates across the SE margin of the Massif Central are in the 20–120 mm kyr−1 (equivalent to mm/ka in the figures) range, and they positively correlate with slope and precipitation. However, the relationship with the steepness index is complex and supports the importance of taking into account spatial variations in parameters (D50, discharge variability k, runoff) controlling the SPM. Overall, the range of denudation rate across the margin can mainly be explained using a simple version of the SPM accounting for spatially heterogeneous runoff. More complex formulations including stochastic discharge and incision thresholds yield poorer performances unless the spatial variations in bedload characteristics controlling incision thresholds are taken into account. Our results highlight the importance of the hypotheses used for such a threshold in SPM application to field studies and notably the impact of actual constraints on bedload size.

International audience

The liver is particularly susceptible to the detrimental effects of a high-fat diet (HFD), rapidly developing lipid accumulation and impaired cellular homeostasis. Recently, dietary nitrate has been shown to attenuate HFD-induced whole body glucose intolerance and liver steatosis, however, the underlying mechanism(s) remain poorly defined. In the current study, we investigated the ability of dietary nitrate to minimize possible impairments in liver mitochondrial bioenergetics following 8 wk of HFD (60% fat) in male C57BL/6J mice. Consumption of a HFD caused whole body glucose intolerance (P < 0.0001), and within the liver, increased lipid accumulation (P < 0.0001), mitochondrial-specific reactive oxygen species emission (P = 0.007), and markers of oxidative stress. Remarkably, dietary nitrate attenuated almost all of these pathological responses. Despite the reduction in lipid accumulation and redox stress (reduced TBARS and nitrotyrosine), nitrate did not improve insulin signaling within the liver or whole body pyruvate tolerance (P = 0.313 HFD vs. HFD + nitrate). Moreover, the beneficial effects of nitrate were independent of changes in weight gain, 5' AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) signaling, mitochondrial content, mitochondrial respiratory capacity and ADP sensitivity or antioxidant protein content. Combined, these data suggest nitrate supplementation represents a potential therapeutic strategy to attenuate hepatic lipid accumulation and decrease mitochondrial ROS emission following HFD, processes linked to improvements in whole body glucose tolerance. However, the beneficial effects of nitrate within the liver do not appear to be a result of increased oxidative capacity or mitochondrial substrate sensitivity.NEW & NOTEWORTHY The mechanism(s) for how dietary nitrate prevents high-fat diet (HFD)-induced glucose intolerance remain poorly defined. We show that dietary nitrate attenuates HFD-induced increases in lipid accumulation, mitochondrial-specific reactive oxygen species (ROS) emission, and markers of oxidative stress within the liver. The beneficial effects of nitrate were independent of changes 5' AMP-activated protein kinase signaling, mitochondrial content/respiratory capacity, or lipid-supported respiratory sensitivity. Combined, these data provide potential mechanisms underlying the therapeutic potential of dietary nitrate.

La mise en œuvre des politiques de conservation de la biodiversité en Amazonie brésilienne n'a pas toujours reposé sur des processus de négociation avec les diverses parties prenantes dans le cadre de stratégies de conservation ascendantes. Historiquement, les agendas environnementaux et de développement, décidés au niveau national, ont eu pour conséquence une perte de la biodiversité, associée à la violation des droits de l'Homme de populations locales. Les productions scientifiques liées à la planification de l'utilisation des terres au Brésil suggèrent que l'absence de référentiels géographiques coordonnés à une planification territoriale globale, entraîne des tensions spatiales qui affectent négativement les politiques de conservation de la biodiversité. L'objectif principal de ce projet est d'analyser les interactions entre « société » et « écosystème » afin de promouvoir une gestion conjointe sous l’angle des systèmes socio-écologiques (SES). La recherche a souhaité tester l'hypothèse des « politiques de dérégulation » en observant les cas de superposition spatiale et d'agrégation de différents produits géographiques pour la planification de l'utilisation des terres dans l'État du Pará au Brésil. L'approche privilégie les relations interdisciplinaires entre le droit et la géomatique. La méthodologie repose sur une l'analyse transversale des deux champs d'études en utilisant des techniques d'interprétation juridique, géomatique et géostatistique.L’objectif de cette tâche est d’identifier et d’évaluer les zones d'intersections géographiques et les doublons entre les zonages règlementaires dans l’État du Pará. Ces travaux précèdent la tâche de vérification juridique de la cohérence règlementaire entre ces zones enchevêtrées.Cette recherche a bénéficié du soutien des "Investissements d'avenir" de l'Agence nationale de la recherche (Ceba, ANR-10-LABX-25-01) et du programme CAPES-COFECUB IBIS.

The evolution of continental relief results from the combined action of tectonic and climatic forcings. These processes do not act continuously but often through punctual events (earthquakes, major floods, landslides) whose integrated action over time (100 Kyr to Myr) leads to the formation of landscapes. The distribution of these extreme events is often described by statistical functions involving power-law relationships between frequency and magnitude, which, coupled with the non-linearity of the geomorphological response and threshold effects for the activation of erosion agents, leads to a complex and often poorly understood relief dynamics.Studying the influence of discharge variability helps to better constrain river incision and long-term relief evolution. The south-eastern margin of the Massif Central (France) is a very interesting target for such investigations because it presents episodes of very intense precipitation focused on the relief resulting in marked differences in the statistical discharges distributions across the landscape. Some theoretical river incision models incorporate such variability (Lague et al., 2005) but they have been confronted with real data only in a limited number of cases (DiBiase et al., 2011; Scherler et al., 2017; Campfort et al., 2020). Here we test these models in the Massif Central area and in particular on Cévennes, Ardèche and Margeride mountains by quantifying denudation rates using cosmogenic nuclides (10Be), characterizing discharges variability and performing morphological analysis on longitudinal rivers profiles.The analysis of 326 river gauging stations allow us to observe a strong gradient in discharge variability from the external SE border to the interior of the Massif Central. The 10Be concentrations measured from river sediments in 36 catchments imply a large variation of denudation rates between 29 mm/kyr and 126 mm/kyr. We compare these denudation rates with the spatial distribution of mean annual precipitations, local relief, slope and concavity index, and also integrate all the observations in the frame of a stochastic threshold incision model. Our results confirm the complex model predictions of non-linear relationships between mean denudation rates and the channel steepness index and their dependence on hydrological variability and run-off.key-words : extreme events, stochastic threshold incision model, denudation rates, discharge variability, morphometric parameters, Massif Central

Background Rotavirus vaccines are effective in preventing severe rotavirus. Haiti introduced 2-dose monovalent (G1P[8]) rotavirus vaccine recommended for infants at 6 and 10 weeks of age in 2014. We calculated the effectiveness of rotavirus vaccine against hospitalization for acute gastroenteritis in Haiti. Methods We enrolled children 6–59 months old admitted May 2014-September 2019 for acute watery diarrhea at any sentinel surveillance hospital. Stool was tested for rotavirus using enzyme immunoassay (EIA) and genotyped with multiplex one-step RT-PCR assay and Sanger sequencing for stratification by genotype. We used a case-negative design where cases were children positive for rotavirus and controls were negative for rotavirus. Only children eligible for vaccination were included and a child was considered vaccinated if vaccine was given ≥ 14 days before enrollment. We used unconditional logistic regression to calculate odds ratios and calculated 2-dose and 1-dose vaccine effectiveness (VE) as (1 - odds ratio) * 100. Results We included 129 (19%) positive cases and 543 (81%) negative controls. Among cases, 77 (60%) were positive for equine-like G3P[8]. Two doses of rotavirus vaccine were 66% (95% CI: 44, 80) effective against hospitalizations due to any strain of rotavirus and 64% (95% CI: 33, 81) effective against hospitalizations due to the equine-like G3P[8] genotype. Conclusions These findings are comparable to other countries in the Americas region. To the best of our knowledge, this is the first VE estimate both against the equine-like G3P[8] genotype and from a Caribbean country. Overall, these results support rotavirus vaccine use and demonstrate the importance of complete vaccination.

Nucleoside analogues are among the most common medications given for the treatment of viral infections and cancers. The therapeutic effectiveness of nucleoside analogues can be dramatically improved by phosphorylation. The ProTide approach was developed using a phosphorylated nucleoside that is masked by esterification with an amino acid and phenol forming a chiral phosphorus center. The biological activity of the ProTides depends, in part, on the stereochemistry at phosphorus, and thus, it is imperative that efficient methods be developed for the chemical synthesis and isolation of diastereomerically pure ProTides. Chiral ProTides are often synthesized by direct displacement of a labile phenol (p-nitrophenol or pentafluorophenol) from a chiral phosphoramidate precursor with the appropriate nucleoside analogue. The ability to produce these chiral products is dictated by the synthesis of the chiral phosphoramidate precursors. The enzyme phosphotriesterase (PTE) from Pseudomonas diminuta is well-known for its high stereoselectivity and broad substrate profile. Screening PTE variants from enzyme evolution libraries enabled the identification of variants of PTE that can stereoselectively hydrolyze the chiral phosphoramidate precursors. The variant G60A-PTE exhibits a 165-fold preference for hydrolysis of the RP isomer, while the variant In1W-PTE has a 1400-fold preference for hydrolysis of the SP isomer. Using these mutants of PTE, the SP and RP isomers were isolated on a preparative scale with no detectable contamination of the opposite isomer. Combining the simplicity of the enzymatic resolution of the precursor with the latest synthetic strategy will facilitate the production of diastereometrically pure nucleotide phosphoramidate prodrugs.

This work enhances our understanding of catchment-scale N budgets by demonstrating the modification and application of a simple method for direct in situ measurements of vadose zone nitrate leaching and attenuation. We developed a soil passive flux meter (SPFM) to measure solute leaching based on a modified design of ion-exchange resin columns, and we tested the design in numerical simulations, laboratory experiments, plot-scale field experiments, and a catchment-scale field deployment. Our design minimized flow divergence around the resin column to attain nearly 100% capture of surface applied tracers in plot- and catchment-scale deployments. We found that mixing resin with native soil and extending the column height 10 cm above the resin layer minimized divergence of soil water around the column, resulting in a field-measured convergence factor (χ) of 1.3 that was consistent with numerical simulations. For catchment-scale testing, SPFMs were used at nine sites in three dominant land uses (crop, pasture, and turf) with known N inputs in two deployments, one during the 4-mo wet season and an additional set during the 8-mo dry season, to obtain integral annual measures of soil nitrate fluxes. In situ measured nitrate leaching determined from the SPFMs was positively correlated with known N inputs ( = 0.55, < 0.05) and attenuation averaged 67% (± 24% SD) of inputs across all sites. Although N inputs explain a large portion of the variability, our results emphasize the importance of both inter- and intra-land use variability in landscape-scale N budgets.

Road mortality poses a major threat to turtle populations. Several studies have suggested that the terrestrial movements associated with nesting increase this risk for females. The Ontario Turtle Conservation Centre (OTCC) is home to the Kawartha Turtle Trauma Centre, which admits 900 or more turtles a year, with road injuries the primary cause of admission. We tested the hypothesis that road mortality in turtles is female-biased using data from injured Midland Painted Turtles (Chrysemys picta marginata), Snapping Turtles (Chelydra serpentina), Blanding’s Turtles (Emydoidea blandingii), and Northern Map Turtles (Graptemys geographica) collected over about 126 000 km2 and admitted to OTCC’s hospital from January 2013 to October 2017. There was no difference in the number of male and female admissions of Midland Painted, Blanding’s, or Snapping Turtles (P > 0.05); however, more female Northern Map Turtles than males were admitted (P < 0.001). Admission of female turtles peaked in June during the nesting season, but male admissions were more evenly distributed throughout the season. Our admissions data provide a temporally unbiased and geographically broad snapshot of turtle–vehicle interactions that can directly inform conservation and management policies. Although our data are not equivalent to mortality rates, these results demonstrate that vehicle strikes can have a substantial impact on both female and male turtles.

The bacterial enzyme phosphotriesterase (PTE) is noted for its ability to hydrolyze many organophosphate compounds, including insecticides and chemical warfare agents. PTE has been the subject of multiple enzyme evolution attempts, which have been highly successful against specific insecticides and the G-type nerve agents. Similar attempts targeting the V-type nerve agents have failed to achieve the same degree of success. Enzyme evolution is an inherently complex problem, which is complicated by synergistic effects, the need to use analogues in high-throughput screening, and a lack of quantitative data to direct future efforts. Previous evolution experiments with PTE have assumed an absence of synergy and minimally screened large libraries, which provides no quantitative information about the effects of individual mutations. Here a systemic approach has been applied to a 28800-member six-site PTE library. The library is screened against multiple V-agent analogues, and a combination of sequence and quantitative activity analysis is used to extract data about the effects of individual mutations. We demonstrate that synergistic relationships dominate the evolutionary landscape of PTE and that analogue activity profiles can be used to identify variants with high activity for substrates. Using these approaches, multiple variants with kcat/ Km values for the hydrolysis of VX that were improved >1500-fold were identified, including one variant that is improved 9200-fold relative to wild-type PTE and is specific for the SP enantiomer of VX. Multiple variants that were highly active for ( SP)-VR were identified, the best of which has a kcat/ Km values that is improved 13400-fold relative to that of wild-type PTE.