Sea star tenacity mediated by a protein that fragments, then aggregates

Hennebert, Elise,Wattiez, Ruddy,Demeuldre, Mé,lanie,Ladurner, Peter,Hwang, Dong Soo,Waite, J. Herbert,Flammang, Patrick National Academy of Sciences 2014 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.111 No.17

<P>Sea stars adhere firmly but temporarily to various substrata as a result of underwater efficient adhesive secretions released by their tube feet. Previous studies showed that this material is mainly made up of proteins, which play a key role in its adhesiveness and cohesiveness. Recently, we solubilized the majority of these proteins and obtained 43 de novo-generated peptide sequences by tandem MS. Here, one of these sequences served to recover the full-length sequence of Sea star footprint protein 1 (Sfp1), by RT-PCR and tube foot transcriptome analysis. Sfp1, a large protein of 3,853 aa, is the second most abundant constituent of the secreted adhesive. By using MS and Western blot analyses, we showed that Sfp1 is translated from a single mRNA and then cleaved into four subunits linked together by disulphide bridges in tube foot adhesive cells. The four subunits display specific protein-, carbohydrate-, and metal-binding domains. Immunohistochemistry and immunocytochemistry located Sfp1 in granules stockpiled by one of the two types of adhesive cells responsible for the secretion of the adhesive material. We also demonstrated that Sfp1 makes up the structural scaffold of the adhesive footprint that remains on the substratum after tube foot detachment. Taken together, the results suggest that Sfp1 is a major structural protein involved in footprint cohesion and possibly in adhesive interactions with the tube foot surface. In recombinant form, it could be used for the design of novel sea star-inspired biomaterials.</P>

The PMIP4 contribution to CMIP6 - Part 3: The last millennium, scientific objective, and experimental design for the PMIP4 <i>past1000</i> simulations

Jungclaus, Johann H.,Bard, Edouard,Baroni, Mé,lanie,Braconnot, Pascale,Cao, Jian,Chini, Louise P.,Egorova, Tania,Evans, Michael,Gonzá,lez-Rouco, J. Fidel,Goosse, Hugues,Hurtt, George C.,Jo Copernicus GmbH 2017 Geoscientific model development Vol.10 No.11

<P><p><strong>Abstract.</strong> The pre-industrial millennium is among the periods selected by the Paleoclimate Model Intercomparison Project (PMIP) for experiments contributing to the sixth phase of the Coupled Model Intercomparison Project (CMIP6) and the fourth phase of the PMIP (PMIP4). The <i>past1000</i> transient simulations serve to investigate the response to (mainly) natural forcing under background conditions not too different from today, and to discriminate between forced and internally generated variability on interannual to centennial timescales. This paper describes the motivation and the experimental set-ups for the PMIP4-CMIP6 <i>past1000</i> simulations, and discusses the forcing agents orbital, solar, volcanic, and land use/land cover changes, and variations in greenhouse gas concentrations. The <i>past1000</i> simulations covering the pre-industrial millennium from 850 Common Era (CE) to 1849<span class='thinspace'></span>CE have to be complemented by <i>historical</i> simulations (1850 to 2014<span class='thinspace'></span>CE) following the CMIP6 protocol. The external forcings for the <i>past1000</i> experiments have been adapted to provide a seamless transition across these time periods. Protocols for the <i>past1000</i> simulations have been divided into three tiers. A default forcing data set has been defined for the Tier 1 (the CMIP6 <i>past1000</i>) experiment. However, the PMIP community has maintained the flexibility to conduct coordinated sensitivity experiments to explore uncertainty in forcing reconstructions as well as parameter uncertainty in dedicated Tier 2 simulations. Additional experiments (Tier 3) are defined to foster collaborative model experiments focusing on the early instrumental period and to extend the temporal range and the scope of the simulations. This paper outlines current and future research foci and common analyses for collaborative work between the PMIP and the observational communities (reconstructions, instrumental data).</p> </P>

Inactivation of Mycobacterium tuberculosis l,d-Transpeptidase Ldt_Mt1by Carbapenems and Cephalosporins

Dubé,e, Vincent,Triboulet, Sé,bastien,Mainardi, Jean-Luc,Ethè,ve-Quelquejeu, Mé,lanie,Gutmann, Laurent,Marie, Arul,Dubost, Lionel,Hugonnet, Jean-Emmanuel,Arthur, Michel American Society for Microbiology 2012 Antimicrobial agents and chemotherapy Vol.56 No.8

<B>ABSTRACT</B><P>The structure ofMycobacterium tuberculosispeptidoglycan is atypical since it contains a majority of 3→3 cross-links synthesized byl,d-transpeptidases that replace 4→3 cross-links formed by thed,d-transpeptidase activity of classical penicillin-binding proteins. Carbapenems inactivate thesel,d-transpeptidases, and meropenem combined with clavulanic acid is bactericidal against extensively drug-resistantM. tuberculosis. Here, we used mass spectrometry and stopped-flow fluorimetry to investigate the kinetics and mechanisms of inactivation of the prototypicM. tuberculosisl,d-transpeptidase LdtMt1by carbapenems (meropenem, doripenem, imipenem, and ertapenem) and cephalosporins (cefotaxime, cephalothin, and ceftriaxone). Inactivation proceeded through noncovalent drug binding and acylation of the catalytic Cys of LdtMt1, which was eventually followed by hydrolysis of the resulting acylenzyme. Meropenem rapidly inhibited LdtMt1, with a binding rate constant of 0.08 μM<SUP>−1</SUP>min<SUP>−1</SUP>. The enzyme was unable to recover from this initial binding step since the dissociation rate constant of the noncovalent complex was low (<0.1 min<SUP>−1</SUP>) in comparison to the acylation rate constant (3.1 min<SUP>−1</SUP>). The covalent adduct resulting from enzyme acylation was stable, with a hydrolysis rate constant of 1.0 × 10<SUP>−3</SUP>min<SUP>−1</SUP>. Variations in the carbapenem side chains affected both the binding and acylation steps, ertapenem being the most efficient LdtMt1inactivator. Cephalosporins also formed covalent adducts with LdtMt1, although the acylation reaction was 7- to 1,000-fold slower and led to elimination of one of the drug side chains. Comparison of kinetic constants for drug binding, acylation, and acylenzyme hydrolysis indicates that carbapenems and cephems can both be tailored to optimize peptidoglycan synthesis inhibition inM. tuberculosis.</P>

Density profile of dark matter haloes and galaxies in the horizon–agn simulation: the impact of AGN feedback

Peirani, Sé,bastien,Dubois, Yohan,Volonteri, Marta,Devriendt, Julien,Bundy, Kevin,Silk, Joe,Pichon, Christophe,Kaviraj, Sugata,Gavazzi, Raphaë,l,Habouzit, Mé,lanie Oxford University Press 2017 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.472 No.2

A new flap combination for reconstruction of lower nasal dorsum and supra-tip skin defects

Mélanie Guesnier,Xavier Claveleau,Marielle Longeac,Isabelle Barthélémy,Nathalie Pham Dang,Arnaud Depeyre 대한성형외과학회 2019 Archives of Plastic Surgery Vol.46 No.5

Repairing surgical defects of the nose is still challenging due to its tridimensional shape and its aesthetic concern. Difficulty in reconstructing nasal subunits lies in their contour, skin texture and limited availability of adjacent skin. For lower nasal dorsum and supra-tip regions, we design a new combined local flap as existing local flaps may give disappointing results. This combination flap was performed on two patients for reconstruction of the lower nasal dorsum area after basal cell carcinoma excision. Size of the excision ranged from 20 to 25 mm diameter and safe margins were obtained. The defects were reconstructed with a local flap that combined a rotation nasal flank flap and a V-Y advancement nasolabial flap. Excision and reconstruction were performed in a one-stage surgery under intravenous sedation and local anesthesia. There were no postoperative complications and no flap loss occurred. Aesthetic and functional results after 6 months postoperatively were satisfying without modification of nasal shape. This flap is reliable and offers interesting functional and aesthetic outcomes. It can be considered as a new reconstruction alternative for supra-tip and lower nasal dorsum skin defects performed in a one-stage procedure under local anesthesia.

Probiotics as Complementary Treatment for Metabolic Disorders

Mélanie Le Barz,Fernando F. Anhê,Thibaut V. Varin,Yves Desjardins,Emile Levy,Denis Roy,Maria C. Urdaci,André Marette 대한당뇨병학회 2015 Diabetes and Metabolism Journal Vol.39 No.4

Over the past decade, growing evidence has established the gut microbiota as one of the most important determinants of metabolic disorders such as obesity and type 2 diabetes. Indeed, obesogenic diet can drastically alter bacterial populations (i.e., dysbiosis) leading to activation of pro-inflammatory mechanisms and metabolic endotoxemia, therefore promoting insulin resistance and cardiometabolic disorders. To counteract these deleterious effects, probiotic strains have been developed with the aim of reshaping the microbiome to improve gut health. In this review, we focus on benefits of widely used probiotics describing their potential mechanisms of action, especially their ability to decrease metabolic endotoxemia by restoring the disrupted intestinal mucosal barrier. We also discuss the perspective of using new bacterial strains such as butyrate-producing bacteria and the mucolytic Akkermansia muciniphila, as well as the use of prebiotics to enhance the functionality of probiotics. Finally, this review introduces the notion of genetically engineered bacterial strains specifically developed to deliver anti-inflammatory molecules to the gut.

Preterm birth is associated with epigenetic programming of transgenerational hypertension in mice

Laurence Dumeige,Mélanie Nehlich,Say Viengchareun,Julie Perrot,Eric Pussard,Marc Lombès,Laetitia Martinerie 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Renal and cardiovascular complications of prematurity are well established, notably the development of hypertension in adulthood. However, the underlying molecular mechanisms remain poorly understood. Our objective was to investigate the impact of prematurity on the ontogenesis of renal corticosteroid pathways, to evaluate its implication in perinatal renal complications and in the emergence of hypertension in adulthood. Swiss CD1 pregnant mice were injected with lipopolysaccharides at 18 days of gestation (E18) to induce prematurity at E18.5. Pups were sacrificed at birth, 7 days and 6 months of life. Second (F2) and third (F3) generations, established by mating prematurely born adult females with wild-type males, were also analyzed. Former preterm males developed hypertension at M6 (P< 0.0001). We found robust activation of renal corticosteroid target gene transcription at birth in preterm mice (αENaC (+45%), Gilz (+85%)), independent of any change in mineralocorticoid or glucocorticoid receptor expression. The offspring of the preterm group displayed increased blood pressure in F2 and F3, associated with increased renal Gilz mRNA expression, despite similar MR or GR expression and plasma corticosteroid levels measured by LC-MS/MS. Gilz promoter methylation measured by methylated DNA immunoprecipitation-qPCR was reduced with a negative correlation between methylation and expression (P=0.0106). Our study demonstrates prematurity-related alterations in renal corticosteroid signaling pathways, with transgenerational inheritance of blood pressure dysregulation and epigenetic Gilz regulation up to the third generation. This study provides a better understanding of the molecular mechanisms involved in essential hypertension, which could partly be due to perinatal epigenetic programming from previous generations.

Head computed tomography for elderly patients with acute altered mental status in the emergency setting: value for decision-making and predictors of abnormal findings

Gerlier Camille,Forster Mélanie,Fels Audrey,Zins Marc,Chatellier Gilles,Ganansia Olivier 대한응급의학회 2022 Clinical and Experimental Emergency Medicine Vol.9 No.4

Objective This study evaluated the impact of head computed tomography (CT) on clinical decision-making about older adults with acute altered mental status (AMS) in the emergency department in terms of CT’s diagnostic yield, emergency department length of stay, and changes in medical strategy. It also attempted to find predictors of an acute imaging abnormality.Methods This was a 1-year, retrospective, single-center observational study of patients aged ≥75 years who underwent noncontrast head CT because of an isolated episode of AMS. The acute positive CT findings were ischemic strokes, hemorrhages, tumors, demyelinating lesions, hydrocephalus, and intracranial infections.Results A total of 594 CTs were performed, of which 38 (6.4%) were positive. The main etiology of AMS was sepsis (29.1%). Changes in medical strategy were more common in patients with a positive CT, and the major changes were ordering additional neuro exams (odds ratio [OR], 95.3; 95% confidence interval [CI], 38.4–233.8; P<0.001), adjusting treatments (OR, 12.2; 95% CI, 5.0–29.5; P<0.001), and referral to a neurologic unit (OR, 7.3; 95% CI, 3.0–17.5; P<0.01). Three factors were significantly associated with a positive outcome: Glasgow Coma Scale <13 (OR, 8.5; 95% CI, 2.3–28.9; P<0.001), head wound (OR, 3.1; 95% CI, 1.1–8.2; P=0.025), and dehydration (OR, 0.3; 95% CI, 0.1–0.4; P=0.021). For elderly patients with a Glasgow Coma Scale ≥13 and no head wound or clinical dehydration, the probability of a positive CT was 0.02 (95% CI, 0.01–0.04). Considering only those patients, the diagnostic yield fell to 1.7%.Conclusion In elderly patients, the causes of AMS are primarily extracerebral. Randomized clinical trials are needed to validate a clinical pathway for selecting patients who require emergent neuroimaging.

Multiple Exposures and Coexposures to Occupational Hazards Among Agricultural Workers: A Systematic Review of Observational Studies

Thi-Hai-Yen Nguyen,Mélanie Bertin,Julie Bodin,Natacha Fouquet,Nathalie Bonvallot,Yves Roquelaure 한국산업안전보건공단 산업안전보건연구원 2018 Safety and health at work Vol.9 No.3

Background: Workers may be exposed to various types of occupational hazards at the same time, potentially increasing the risk of adverse health outcomes. The aim of this review was to analyze the effects of multiple occupational exposures and coexposures to chemical, biomechanical, and physical hazards on adverse health outcomes among agricultural workers. Methods: Articles published in English between 1990 and 2015 were identified using five popular databases and two complementary sources. The quality of the included publications was assessed using the methodology developed by the Effective Public Health Practice Project assessment tool for quantitative studies. Results: Fifteen articles were included in the review. Multiple chemical exposures were significantly associated with an increased risk of respiratory diseases, cancer, and DNA and cytogenetic damage. Multiple physical exposures seemed to increase the risk of hearing loss, whereas coexposures to physical and biomechanical hazards were associated with an increased risk of musculoskeletal disorders among agricultural workers. Conclusion: Few studies have explored the impact of multiple occupational exposures on the health of agricultural workers. A very limited number of studies have investigated the effect of coexposures among biomechanical, physical, and chemical hazards on occupational health, which indicates a need for further research in this area.

Ligamentoplasty with interposition of the proximal interphalangeal joint in the treatment of unicondylar osteochondral defects: a cadaveric feasibility study

Jean-Charles Hery,Baptiste Picart,Mélanie Malherbe,Christophe Hulet,Aude Lombard 대한성형외과학회 2021 Archives of Plastic Surgery Vol.48 No.6

Background Injuries to the proximal interphalangeal (PIP) joint are common and complex. However, the treatment of osteochondral defects of the head of the proximal phalanx has rarely been described. Herein, we propose a new technique for the management of unicondylar defects of the proximal phalanx that can restore joint amplitudes and provide PIP stability. Methods In this cadaveric feasibility study, unicondylar defects were generated using striking wedges and chisels. First, a transverse tunnel measuring 2 mm in diameter passing through the head of the proximal phalanx was made. A second tunnel at the base of the middle phalanx with the same diameter was then created. The hemitendon of the flexor carpi radialis graft was passed through each of these tunnels. The proximal end of the graft was interposed in the area with a loss of bone substance. The ligamentoplasty was then tensed and fixed by two anchors on the proximal phalanx. Joint amplitudes and frontal stability were measured preoperatively and postoperatively. Results There was no significant change in the joint’s range of motion: preoperatively, the mean mobility arcs were –2° to 113.80°, and they were –2° to 110° after the procedure (P= 0.999). There was no significant difference in joint stability (P>0.05). Conclusions Ligamentoplasty with PIP interposition appears to be a possible solution for the management of unicondylar defects of the proximal phalanx. An evaluation of clinical results is planned in order to definitively confirm the validity of this procedure.