Etude de l'influence de voies électroniques mortes ou bruyantes sur les performances du système de déclenchement dimuons de l'expérience ALICE

ALICE, rapport JANU

Intégrales de chemin et fentes de Young

Stage Janus 0

Research priorities for liver glycogen storage disease:An international priority setting partnership with the James Lind Alliance

The international liver glycogen storage disease (GSD) priority setting partnership (IGSDPSP) was established to identify the top research priorities in this area. The multiphase methodology followed the principles of the James Lind Alliance (JLA) guidebook. An international scoping survey in seven languages was distributed to patients, carers, and healthcare professionals to gather uncertainties, which were consolidated into summary questions. The existing literature was reviewed to ensure that the summary questions had not yet been answered. A second survey asked responders to prioritize these summary questions. A final shortlist of 22 questions was discussed during an international multi-stakeholder workshop, and a consensus was reached on the top 11 priorities using an adapted nominal group technique.In the first survey, a total of 1388 questions were identified from 763 responders from 58 countries. These original uncertainties were refined into 72 summary questions for a second prioritization survey. In total 562 responders from 58 countries answered the second survey. From the second survey, the top 10 for patients, carers and healthcare professionals was identified and this shortlist of 22 questions was taken to the final workshop. During the final workshop, participants identified the worldwide top 11 research priorities for liver GSD. In addition, a top three research priorities per liver GSD subtype was identified.This unique priority setting partnership is the first international, multilingual priority setting partnership focusing on ultra-rare diseases. This process provides a valuable resource for researchers and funding agencies to foster interdisciplinary and transnational research projects with a clear benefit for patients

Effect of cadmium on cytosine hydroxymethylation in gastropod hepatopancreas

5-Hydroxymethylcytosine (5hmC) is an important, yet poorly understood epigenetic DNA modification, especially in invertebrates. Aberrant genome-wide 5hmC levels have been associated with cadmium (Cd) exposure in humans, but such information is lacking for invertebrate bioindicators. Here, we aimed to determine whether this epigenetic mark is present in DNA of the hepatopancreas of the land snail Cantareus aspersus and is responsive to Cd exposure. Adult snails were reared under laboratory conditions and exposed to graded amounts of dietary cadmium for 14 days. Weight gain was used as a sublethal endpoint, whereas survival as a lethal endpoint. Our results are the first to provide evidence for the presence of 5hmC in DNA of terrestrial mollusks; 5hmC levels are generally low with the measured values falling below 0.03%. This is also the first study to investigate the interplay of Cd with DNA hydroxymethylation levels in a non-human animal study system. Cadmium retention in the hepatopancreas of C. aspersus increased from a dietary Cd dose of 1 milligram per kilogram dry weight (mg/kg d. wt). For the same treatment, we identified the only significant elevation in percentage of samples with detectable 5hmC levels despite the lack of significant mortalities and changes in weight gain among treatment groups. These findings indicate that 5hmC is an epigenetic mark that may be responsive to Cd exposure, thereby opening a new aspect to invertebrate environmental epigenetics

Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers

"This is the peer reviewed version of the following article: Gottselig, N., W. Amelung, J. W. Kirchner, R. Bol, W. Eugster, S. J. Granger, C. Hernández-Crespo, et al. 2017. Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers. Global Biogeochemical Cycles 31 (10). American Geophysical Union (AGU): 1592 1607. doi:10.1002/2017gb005657, which has been published in final form at https://doi.org/10.1002/2017GB005657. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Biogeochemical cycling of elements largely occurs in dissolved state, but many elements may also be bound to natural nanoparticles (NNP, 1-100 nm) and fine colloids (100-450 nm). We examined the hypothesis that the size and composition of stream water NNP and colloids vary systematically across Europe. To test this hypothesis, 96 stream water samples were simultaneously collected in 26 forested headwater catchments along two transects across Europe. Three size fractions (similar to 1-20 nm, >20-60 nm, and >60 nm) of NNP and fine colloids were identified with Field Flow Fractionation coupled to inductively coupled plasma mass spectrometry and an organic carbon detector. The results showed that NNP and fine colloids constituted between 2 +/- 5% (Si) and 53 +/- 21% (Fe; mean +/- SD) of total element concentrations, indicating a substantial contribution of particles to element transport in these European streams, especially for P and Fe. The particulate contents of Fe, Al, and organic C were correlated to their total element concentrations, but those of particulate Si, Mn, P, and Ca were not. The fine colloidal fractions >60 nm were dominated by clay minerals across all sites. The resulting element patterns of NNP <60 nm changed from North to South Europe from Fe-to Ca-dominated particles, along with associated changes in acidity, forest type, and dominant lithology.The authors gratefully acknowledge the assistance of the following people in locating suitable sampling sites, contacting site operators, performing the sampling, and providing data: A. Avila Castells (Autonomous University of Barcelona), R. Batalla (University of Lleida), P. Blomkvist (Swedish University of Agricultural Sciences), H. Bogena (Julich Research Center), A.K. Boulet (University of Aveiro), D. Estany (University of Lleida), F. Garnier (French National Institute of Agricultural Research), H.J. Hendricks-Franssen (Research Center Julich), L. JacksonBlake (James Hutton Institute, NIVA), T. Laurila (Finnish Meteorological Institute), A. Lindroth (Lund University), M.M. Monerris (Universitat Politecnica de Valencia), M. Ottosson Lofvenius (Swedish University of Agricultural Sciences), I. Taberman (Swedish University of Agricultural Sciences), F. Wendland (Research Center Julich), T. Zetterberg (Swedish University of Agricultural Sciences and The Swedish Environmental Research Institute, IVL) and further unnamed contributors. The Swedish Infrastructure for Ecosystem Science (SITES) and the Swedish Integrated Monitoring, the latter financed by the Swedish Environmental Protection Agency, and ICOS Sweden have supported sampling and provided data for the Swedish sites. J.J.K. gratefully acknowledges the support from CESAM (UID/AMB/50017/2013), funded by the FCT/MCTES (PIDDAC) with cofunding by FEDER through COMPETE. N.G. gratefully acknowledges all those who contributed to organizing and implementing the continental sampling. The raw data can be found at http://hdl.handle.net/2128/14937. This project was partly funded by the German Research Foundation (DFG KL2495/1-1).Gottselig, N.; Amelung, W.; Kirchner, J.; Bol, R.; Eugster, W.; Granger, S.; Hernández Crespo, C.... 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Subglacial discharge at tidewater glaciers revealed by seismic tremor

Subglacial discharge influences glacier basal motion and erodes and redeposits sediment. At tidewater glacier termini, discharge drives submarine terminus melting, affects fjord circulation, and is a central component of proglacial marine ecosystems.Subglacial discharge influences glacier basal motion and erodes and redeposits sediment. At tidewater glacier termini, discharge drives submarine terminus melting, affects fjord circulation, and is a central component of proglacial marine ecosystems. However, our present inability to track subglacial discharge and its variability significantly hinders our understanding of these processes. Here we report observations of hourly to seasonal variations in 1.5–10 Hz seismic tremor that strongly correlate with subglacial discharge but not with basal motion, weather, or discrete icequakes. Our data demonstrate that vigorous discharge occurs from tidewater glaciers during summer, in spite of fast basal motion that could limit the formation of subglacial conduits, and then abates during winter. Furthermore, tremor observations and a melt model demonstrate that drainage efficiency of tidewater glaciers evolves seasonally. Glaciohydraulic tremor provides a means by which to quantify subglacial discharge variations and offers a promising window into otherwise obscured glacierized environments.We thank the U.S. National Science Foundation for supporting data collection at Yahtse Glacier through grant EAR-0810313. T.C.B. was substantially supported by a postdoctoral fellowship from the University of Texas Institute for Geophysics. J.M.A. was supported by Alaska NASA EPSCoR Program (NNX13AB28A). S.O. was supported by the U.S. Geological Survey Climate and Land Use Change Mission and the U.S. Department of Interior Alaska Climate Science Center. Seismic instrumentationwas provided by the PASSCAL polar program of the Incorporated Research Institutions for Seismology (IRIS). Jamie Bradshaw and Marci Beitch assisted in the Mendenhall Glacier data collection effort. Two anonymous reviewers helped to improve the manuscript. Seismic data used in this study are archived at the Incorporated Research Institutions for Seismology Data Management Center (IRIS DMC, http://www.iris.edu/dms/nodes/dmc/). Stream gaging data for the Mendenhall River and Nugget Creek are available though http://waterdata.usgs.gov/ak/nwis/dv/?site_no=15052500 and http://waterdata.usgs.gov/ak/nwis/dv/?site_no=15052495. Any additional data may be obtained from T.C.B. ([email protected]). Use of trade, product, or firm names is for descriptive purposes only and does not imply endorsement by the U.S. Government. The Editor thanks Gordon Hamilton and an anonymous reviewer for their assistance in evaluating this paper.Ye

Biology and biotechnology of Trichoderma

Fungi of the genus Trichoderma are soilborne, green-spored ascomycetes that can be found all over the world. They have been studied with respect to various characteristics and applications and are known as successful colonizers of their habitats, efficiently fighting their competitors. Once established, they launch their potent degradative machinery for decomposition of the often heterogeneous substrate at hand. Therefore, distribution and phylogeny, defense mechanisms, beneficial as well as deleterious interaction with hosts, enzyme production and secretion, sexual development, and response to environmental conditions such as nutrients and light have been studied in great detail with many species of this genus, thus rendering Trichoderma one of the best studied fungi with the genome of three species currently available. Efficient biocontrol strains of the genus are being developed as promising biological fungicides, and their weaponry for this function also includes secondary metabolites with potential applications as novel antibiotics. The cellulases produced by Trichoderma reesei, the biotechnological workhorse of the genus, are important industrial products, especially with respect to production of second generation biofuels from cellulosic waste. Genetic engineering not only led to significant improvements in industrial processes but also to intriguing insights into the biology of these fungi and is now complemented by the availability of a sexual cycle in T. reesei/Hypocrea jecorina, which significantly facilitates both industrial and basic research. This review aims to give a broad overview on the qualities and versatility of the best studied Trichoderma species and to highlight intriguing findings as well as promising applications

Trials

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. PARTICIPANTS: Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate 5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. INTERVENTION AND COMPARATOR: The four experimental treatments planned in protocol version 1.2 (April 8(th), 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. MAIN OUTCOME: The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. RANDOMISATION: Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). BLINDING (MASKING): This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. TRIAL STATUS: This describes the Version 1.2 (April 8(th), 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15(th), 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15(th), 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 22(nd), 2020 (Identifier: NCT04356495): and on EudraCT on April 10(th), 2020 (Identifier: 2020-001435-27). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2)