Direct Electrochemistry of Redox Enzymes as a Tool for Mechanistic Studies

International audienceThis review regards the use of dynamic electrochemistry to study the mechanism of redox enzymes, with exclusive emphasis on the configuration where the protein is adsorbed onto an electrode and electron tranfer is direct

Energy expenditure of extreme competitive mountaineering skiing

Purpose: Multi-hour ski mountaineering energy balance may be negative and intake below recommendations. Methods: Athletes on the ‘Patrouille des Glaciers' racecourses (17 on course Z, 27km, +2,113m; 11 on course A, 26km, +1,881m) volunteered. Pre-race measurements included body mass, stature, VO2max, and heart rate (HR) vs VO2 at simulated altitude; race measurements HR, altitude, incline, location, and food and drink intake (A). Energy expenditure (EE) was calculated from altitude corrected HR derived VO2. Results: Race time was 5h 7min±44min (mean±SD, Z) and 5h 51min±53min (A). Subjects spent 19.2±3.2MJ (Z), respectively, 22.6±2.9MJ (A) during the race. Energy deficit was −15.5±3.9MJ (A); intake covered 20±7% (A). Overall energy cost of locomotion (EC) was 9.9±1.3Jm−1kg−1 (Z), 8.0±1.0Jm−1kg−1 (A). Uphill EC was 11.7±1Jm−1kg−1 (Z, 13% slope) and 15.7±2.3Jm−1kg−1 (A, 19% slope). Race A subjects lost −1.5±1.1kg, indicating near euhydration. Age, body mass, gear mass, VO2max and EC were significantly correlated with performance; energy deficit was not. Conclusions: Energy expenditure and energy deficit of a multi-hour ski mountaineering race are very high and energy intake is below recommendations

Sociologie du religieux

Danièle Hervieu-Léger, directrice d’études Après plusieurs années pendant lesquelles le séminaire a été consacré à l’exploration sociologique des formes contemporaines de la religiosité et à l’étude des formes de communalisation émergentes, à l’intérieur aussi bien qu’à l’extérieur des grandes traditions, le séminaire a été marqué – en ce qui concerne la première partie de l’année (jusqu’en mars) – par une reprise de la question des institutions religieuses en modernité. Plus précisément, dan..

Sociologie du religieux

Daniele Hervieu-Léger, directrice d’études La scène religieuse contemporaine est caractérisée, en terrain chrétien, par l’extraordinaire expansion, à l’échelle planétaire, de mouvements nouveaux issus pour l’essentiel du tronc protestant (plus spécifiquement : de sa branche pentecôtiste), mais qui prolifèrent également, à travers la poussée charismatique, dans les mondes catholiques. En Afrique, en Amérique latine, en Asie, mais également en Europe et dans l’ensemble des sociétés occidentales..

Combining experimental and theoretical methods to learn about the reactivity of gas-processing metalloenzymes

International audienceAfter enzymes were first discovered in the late XIX century, and for the first seventy years of enzymology, kinetic experiments were the only source of information about enzyme mechanisms. Over the following fifty years, these studies were taken over by approaches that give information at the molecular level, such as crystallography, spectroscopy and theoretical chemistry (as emphasized by the Nobel Prize in Chemistry awarded last year to M. Karplus, M. Levitt and A. Warshel). In this review, we thoroughly discuss the interplay between the information obtained from theoretical and experimental methods, by focussing on enzymes that process small molecules such as H 2 or CO 2 (hydrogenases, CO-dehydrogenase and carbonic anhydrase), and that are therefore relevant in the context of energy and environment. We argue that combining theoretical chemistry (DFT, MD, QM/MM) and detailed investigations that make use of modern kinetic methods, such as protein film voltammetry, is an innovative way of learning about individual steps and/or complex reactions that are part of the catalytic cycles. We illustrate this with recent results from our labs and others, including studies of gas transport along substrate channels, long range proton transfer, and mechanisms of catalysis, inhibition or inactivation. Broader context Some reactions which are very important in the context of energy and environment, such as the conversion between CO and CO2 , or H+ and H2 , are catalyzed in living organisms by large and complex enzymes that use inorganic active sites to transform substrates, chains of redox centers to transfer electrons, ionizable amino acids to transfer protons, and networks of hydrophobic cavities to guide the diffusion of substrates and products within the protein. This highly sophisticated biological plumbing and wiring makes turnover frequencies of thousands of substrate molecules per second possible. Understanding the molecular details of catalysis is still a challenge. We explain in this review how a great deal of information can be obtained using an interdisciplinary approach that combines state-of-the art kinetics and computational chemistry. This differs from—and complements—the more traditional strategies that consist in trying to see the catalytic intermediates using methods that rely on the interaction between light and matter, such as X-ray diffraction and spectroscopic techniques

Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation

Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3&beta;/4E-BP1, and muscle atrophy, including TNF&alpha;/SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 &plusmn; 0.2 years) and 16 older (70 &plusmn; 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40&ndash;45% in the type II muscle fibers. TNF&alpha; and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3&beta; were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNF&alpha;, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation.<br /

Systematic Review of Biopsychosocial Prognostic Factors for Return to Work After Acute Orthopedic Trauma: A 2020 Update

ObjectiveTo provide updated evidence on prognostic factors for return to work (RTW) in the early and late phases after acute orthopedic trauma from a biopsychosocial perspective.MethodsA systematic review of articles indexed in the MEDLINE, CINAHL, and Embase databases between 2010 and 2020 was performed. The inclusion criteria were cohort studies of employed populations sustaining acute orthopedic trauma with follow-up data on RTW. Biopsychosocial prognostic factors for RTW must be reported in the multiple regression models and divided into early (≤ 6 months) and late phases (&gt; 6 months) postinjury. Two reviewers performed study selection, assessed the risk of bias and quality using the Quality in Prognosis Studies (QUIPS) tool and the Newcastle–Ottawa Scale (NOS), and extracted data independently.ResultsThirty articles were included with a follow-up period of 1–58 months. Based on the QUIPS tool, 7 studies (23%) were considered to have a low risk of bias, and 21 studies (70%) were considered to have a moderate risk of bias. Based on the NOS, the quality was high in 87% of the included studies. The RTW rates ranged from 22% to 74% in the early phase and from 44% to 94% in the late phase. In the early phase, strong evidence was found for injury severity. In the late phase, strong evidence was found for age, injury severity, level of pain, self-efficacy, educational level, blue-collar work, and compensation status; moderate evidence was found for recovery expectations and physical workload. There was limited or inconsistent evidence for the other factors.ConclusionBased on the levels of evidence, injury severity should be considered as one of the key barriers to RTW in the early and late phases postinjury. This finding underlines the need for serious injury prevention efforts. Our results also emphasize the multifaceted actions of the biopsychosocial model to facilitate RTW: promoting policies for older injured workers, improving access to medical and rehabilitation facilities, and adapting physical workload. Multiple other factors are likely important but require additional high-quality studies to assess their role in the RTW process

Design and synthesis of triphenylphosphonium-porphyrin@xylan nanoparticles for anticancer photodynamic therapy

Most photosensitizers (PS) suffer from a lack of water solubility and from a low selectivity toward tumor cells. Delivery systems using nanoparticles make it possible to improve PS water solubility, and also tumor targeting via the enhanced permeability and retention (EPR) effect. Among the organelles, mitochondria are attractive target sites for drug-delivery strategies since they perform a variety of key cellular processes. Our study was aimed at synthesizing nanoparticles consisting of xylan-carrying porphyrins attached to a triphenylphosphonium moiety, in order to enhance the PDT effect through mitochondrial targeting. Hybrid nanoparticles were designed that consisted of a silica core coated with xylan substituted with porphyrin derivatives carrying a triphenylphosphonium moiety. These hybrid nanoparticles have been constructed, along with their counterparts devoid of silica core, taking into consideration the controversy surrounding the use of silica nanoparticles. Phototoxicity experiments, conducted against the HCT-116 and HT-29 colorectal cancer cell lines, showed that nanoparticles with porphyrins bearing a triphenylphosphonium moiety exhibited an enhanced photocytotoxic effect in comparison with free porphyrin or nanoparticles with porphyrins without the triphenylphosphonium moiety

Design and synthesis of triphenylphosphonium-porphyrin@xylan nanoparticles for anticancer photodynamic therapy

Most photosensitizers (PS) suffer from a lack of water solubility and from a low selectivity toward tumor cells. Delivery systems using nanoparticles make it possible to improve PS water solubility, and also tumor targeting via the enhanced permeability and retention (EPR) effect. Among the organelles, mitochondria are attractive target sites for drug-delivery strategies since they perform a variety of key cellular processes. Our study was aimed at synthesizing nanoparticles consisting of xylan-carrying porphyrins attached to a triphenylphosphonium moiety, in order to enhance the PDT effect through mitochondrial targeting. Hybrid nanoparticles were designed that consisted of a silica core coated with xylan substituted with porphyrin derivatives carrying a triphenylphosphonium moiety. These hybrid nanoparticles have been constructed, along with their counterparts devoid of silica core, taking into consideration the controversy surrounding the use of silica nanoparticles. Phototoxicity experiments, conducted against the HCT-116 and HT-29 colorectal cancer cell lines, showed that nanoparticles with porphyrins bearing a triphenylphosphonium moiety exhibited an enhanced photocytotoxic effect in comparison with free porphyrin or nanoparticles with porphyrins without the triphenylphosphonium moiety

A 2015 International Geomagnetic Reference Field (IGRF) candidate model based on <i>Swarm’s</i> experimental absolute magnetometer vector mode data

International audienceEach of the three satellites of the European Space Agency Swarm mission carries an absolute scalar magnetometer (ASM) that provides the nominal 1-Hz scalar data of the mission for both science and calibration purposes. These ASM instruments, however, also deliver autonomous 1-Hz experimental vector data. Here, we report on how ASM-only scalar and vector data from the Alpha and Bravo satellites between November 29, 2013 (a week after launch) and September 25, 2014 (for on-time delivery of the model on October 1, 2014) could be used to build a very valuable candidate model for the 2015.0 International Geomagnetic Reference Field (IGRF). A parent model was first computed, describing the geomagnetic field of internal origin up to degree and order 40 in a spherical harmonic representation and including a constant secular variation up to degree and order 8. This model was next simply forwarded to epoch 2015.0 and truncated at degree and order 13. The resulting ASM-only 2015.0 IGRF candidate model is compared to analogous models derived from the mission's nominal data and to the now-published final 2015.0 IGRF model. Differences among models mainly highlight uncertainties enhanced by the limited geographical distribution of the selected data set (essentially due to a lack of availability of data at high northern latitude satisfying nighttime conditions at the end of the time period considered). These appear to be comparable to differences classically observed among IGRF candidate models. These positive results led the ASM-only 2015.0 IGRF candidate model to contribute to the construction of the final 2015.0 IGRF model