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Jaspard E.,UniversitedAngers | Jaspard E.,French National Institute for Agricultural Research | Jaspard E.,Agrocampus Ouest | Hunault G.,UniversitedAngers
PLoS ONE | Year: 2014

Late Embryogenesis Abundant proteins (LEAPs) comprise several diverse protein families and are mostly involved in stress tolerance. Most of LEAPs are intrinsically disordered and thus poorly functionally characterized. LEAPs have been classified and a large number of their physico-chemical properties have been statistically analyzed. LEAPs were previously proposed to be a subset of a very wide family of proteins called hydrophilins, while a domain called WHy (Water stress and Hypersensitive response) was found in LEAP class 8 (according to our previous classification). Since little is known about hydrophilins and WHy domain, the cross-analysis of their amino acids physico-chemical properties and amino acids usage together with those of LEAPs helps to describe some of their structural features and to make hypothesis about their function. Physico-chemical properties of hydrophilins and WHy domain strongly suggest their role in dehydration tolerance, probably by interacting with water and small polar molecules. The computational analysis reveals that LEAP class 8 and hydrophilins are distinct protein families and that not all LEAPs are a protein subset of hydrophilins family as proposed earlier. Hydrophilins seem related to LEAP class 2 (also called dehydrins) and to Heat Shock Proteins 12 (HSP12). Hydrophilins are likely unstructured proteins while WHy domain is structured. LEAP class 2, hydrophilins and WHy domain are thus proposed to share a common physiological role by interacting with water or other polar/charged small molecules, hence contributing to dehydration tolerance. © 2014 Jaspard, Hunault.


Kremer H.,Hopitaux Universitaires Of Strasbourg | Kremer H.,University of Strasbourg | Baron-Menguy C.,Hopitaux Universitaires Of Strasbourg | Baron-Menguy C.,French Institute of Health and Medical Research | And 9 more authors.
Critical Care Medicine | Year: 2011

Objectives: The mechanisms by which human serum albumin might protect against sepsis-induced organ dysfunction and improve survival are not elucidated. The present study was designed to assess the effects of two concentrations of human serum albumin on endotoxin-induced mortality as well as on endothelial and organ dysfunctions in both mouse and cell models. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratories. Subjects: Swiss mice (n = 10-15/group) were injected with either lipopolysaccharide or vehicle. Four and 12 hrs later, mice were infused or not with human serum albumin HSA (4% or 20%, 10 mL/kg) or normal saline (0.9% NaCl, 30 mL/kg). Human uterine vein endothelial cells were exposed to both lipopolysaccharide and tumor necrosis factor-α during 8 hrs in the presence or absence of human serum albumin (4% or 20%). Measurements and Main Results: Mice survival, reactivity of mesenteric arteries, and Western blot protein analysis were assessed. Circulating endothelin-1, gluthatione, gluthatione disulfide, and creatinine plasma levels were measured. Nitric oxide production, oxidative, and nitrosative stresses were also measured in situ in endothelial cells. Human serum albumin 4%, but not human serum albumin 20% or normal saline solution, improved survival time of endotoxemic mice. Furthermore, human serum albumin 4% activated endothelial nitric oxide synthase and restored lipopolysaccharide-impaired flow-dependent endothelial dilation in mesenteric arteries. This was associated with a downregulation of nuclear factor κB and an upregulation of nuclear respiratory factor-2 and heme oxygenase-1. Human serum albumin 4% reduced lipopolysaccharide-induced renal dysfunction, enhanced endothelin-1 production and glutathione plasmatic levels, whereas human serum albumin 20% increased gluthatione disulfide. Furthermore, human serum albumin 4% but not 20% blunted lipopolysaccharide-tumor necrosis factor-α-induced oxidative and nitrosative stresses in endothelial cells and increased their gluthatione levels. Conclusions: The present data confirm a protective effect of 4% human serum albumin treatment both on mice survival and endothelial dysfunction by inhibiting inflammatory and oxidative stress pathways induced by endotoxins. Conversely, higher concentrations of human serum albumin were detrimental suggesting a dose-dependent effect. Copyright © 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Tabah A.,The Royal Brisbane and Womens Hospital | Tabah A.,University of Queensland | de Waele J.,Ghent University | Lipman J.,The Royal Brisbane and Womens Hospital | And 10 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2015

Objectives: There is little evidence and few guidelines to inform the most appropriate dosing and monitoring for antimicrobials in the ICU. We aimed to survey current practices around the world. Methods: An online structured questionnaire was developed and sent by e-mail to obtain information on local antimicrobial prescribing practices for glycopeptides, piperacillin/tazobactam, carbapenems, aminoglycosides and colistin. Results: A total of 402 professionals from 328 hospitals in 53 countries responded, of whom 78%were specialists in intensive care medicine (41% intensive care, 30% anaesthesiology, 14% internal medicine) and 12% were pharmacists. Vancomycin was used as a continuous infusion in 31% of units at a median (IQR) daily dose of 25 (25-30) mg/kg. Piperacillin/tazobactam was used as an extended infusion by 22% and as a continuous infusion by 7%. An extended infusion of carbapenem (meropenem or imipenem) was used by 27% and a continuous infusion by 5%. Colistin was used at a daily dose of 7.5 (3.9-9)million IU (MIU)/day, predominantly as a short infusion. The most commonly used aminoglycosides were gentamicin (55%) followed by amikacin (40%), with administration as a single daily dose reported in 94%of the cases. Gentamicinwas used at a daily dose of 5 (5-6) mg/day and amikacin at a daily dose of 15 (15-20) mg/day. Therapeutic drug monitoring of vancomycin, piperacillin/ tazobactamandmeropenemwas used by 74%, 1% and 2% of the respondents, respectively. Peak aminoglycoside concentrations were sampled daily by 28% and trough concentrations in all patients by 61% of the respondents. Conclusions:We foundwide variability in reported practices for antibiotic dosing andmonitoring. Research is required to develop evidence-based guidelines to standardize practices. © The Author 2015.


Ramond A.,UniversitedAngers | Bouton C.,UniversitedAngers | Richard I.,UniversitedAngers | Richard I.,Angers University Hospital Center | And 7 more authors.
Family Practice | Year: 2011

Background: Low back pain (LBP) is a major public health problem, often encountered in primary care. Guidelines recommend early identification of psychosocial factors that could prevent recovery from acute LBP. Methods: To review the evidence on the prognostic value of psychosocial factors on transition from acute to chronic non-specific LBP in the adult general population. Systematic review is the design of the study. A systematic search was undertaken for prospective studies dealing with psychosocial risk factors for poor outcome of LBP in primary care, screening PuBmed, PsychInfo and Cochrane Library databases. The methodological quality of studies was assessed independently by two reviewers using standardized criteria before analysing their main results. Results: Twenty-three papers fulfilled the inclusion criteria, covering 18 different cohorts. Sixteen psychosocial factors were analysed in three domains: social and socio-occupational, psychological and cognitive and behavioural. Depression, psychological distress, passive coping strategies and fear-avoidance beliefs were sometimes found to be independently linked with poor outcome, whereas most social and socio-occupational factors were not. The predictive ability of a patient's self-perceived general health at baseline was difficult to interpret because of biomedical confounding factors. The initial patient's or care provider's perceived risk of persistence of LBP was the factor that was most consistently linked with actual outcome. Conclusion: Few independent psychosocial risk factors have been demonstrated to exist. Randomized clinical trials aimed at modifying these factors have shown little impact on patient prognosis. Qualitative research might be valuable to explore further the field of LBP and to define new management strategies. © The Author 2010. Published by Oxford University Press. All rights reserved.


Chinier E.,University of Angers | Chinier E.,UniversitedAngers | N'Guyen S.,University of Angers | N'Guyen S.,Angers University Hospital Center | And 6 more authors.
PLoS ONE | Year: 2014

Background: Motor imagery is considered as a promising therapeutic tool for rehabilitation of motor planning problems in patients with cerebral palsy. However motor planning problems may lead to poor motor imagery ability. Aim: The aim of this functional magnetic resonance imaging study was to examine and compare brain activation following motor imagery tasks in patients with hemiplegic cerebral palsy with left or right early brain lesions. We tested also the influence of the side of imagined hand movement. Method: Twenty patients with clinical hemiplegic cerebral palsy (sixteen males, mean age 12 years and 10 months, aged 6 years 10 months to 20 years 10 months) participated in this study. Using block design, brain activations following motor imagery of a simple opening-closing hand movement performed by either the paretic or nonparetic hand was examined. Results: During motor imagery tasks, patients with early right brain damages activated bilateral fronto-parietal network that comprise most of the nodes of the network well described in healthy subjects. Inversely, in patients with left early brain lesion brain activation following motor imagery tasks was reduced, compared to patients with right brain lesions. We found also a weak influence of the side of imagined hand movement. Conclusion: Decreased activations following motor imagery in patients with right unilateral cerebral palsy highlight the dominance of the left hemisphere during motor imagery tasks. This study gives neuronal substrate to propose motor imagery tasks in unilateral cerebral palsy rehabilitation at least for patients with right brain lesions. © 2014 Chinier et al.


Lardy S.,University of Lyon | Lardy S.,UniversiteLyon 1 | Lardy S.,CNRS Biometry and Evolutionary Biology Laboratory | Lardy S.,UniversitedAngers | And 10 more authors.
Ecology | Year: 2015

Sociality should evolve when the fitness benefits of group living outweigh the costs. Theoretical models predict an optimal group size maximizing individual fitness. However, beyond the number of individuals present in a group, the characteristics of these individuals, like their sex, are likely to affect the fitness payoffs of group living. Using 20 years of individually based data on a social mammal, the Alpine marmot (Marmota marmota), we tested for the occurrence of an optimal group size and composition, and for sex-specific effects of group characteristics on fitness. Based on lifetime data of 52 males and 39 females, our findings support the existence of an optimal group size maximizing male fitness and an optimal group composition maximizing fitness of males and females. Additionally, although group characteristics (i.e., size, composition and instability) affecting male and female fitness differed, fitness depended strongly on the number of same-sex subordinates within the social group in the two sexes. By comparing multiple measures of social group characteristics and of fitness in both sexes, we highlighted the sex-specific determinants of fitness in the two sexes and revealed the crucial role of intrasexual competition in shaping social group composition. © 2015 by the Ecological Society of America.


El Haj M.,UniversitedAngers | Postal V.,University of Bordeaux Segalen | Le Gall D.,UniversitedAngers | Allain P.,UniversitedAngers
Memory | Year: 2011

Using the autobiographical directed forgetting method (Barnier et al., 2007), the present paper addressed the intentional inhibitory processes of episodic and semantic autobiographical memory in Alzheimer's disease (AD). Mild AD patients and healthy elderly people were instructed to either forget or to continue remembering previously generated autobiographical events. In a later recall test they were asked to reconstruct the early-generated memories regardless of the forget/remember instruction. Autobiographical reconstruction was further distributed into episodic and semantic memories. Results showed no forget instruction effect on episodic or semantic autobiographical recall with AD patients, whereas healthy elderly people were able to inhibit only episodic autobiographical memories. The findings suggest an impairment of the intentional inhibitory processes in autobiographical memory with AD and a relative preservation of these mechanisms with normal ageing. They also demonstrate an earlier decline in the intentional inhibitory processes compared to the autobiographical deterioration in AD. © 2011 Copyright Psychology Press.


Illouz F.,Angers University Hospital Center | Braun D.,University of Bonn | Briet C.,Hopitaux Universitaires Paris Sud | Schweizer U.,University of Bonn | And 3 more authors.
European Journal of Endocrinology | Year: 2014

Tyrosine kinase inhibitors (TKIs) are currently used by most oncologists. Among their side effects, thyroid dysfunctions are nowadays clearly observed. Whereas changes in thyroid function tests have been originally described with sunitinib, we now know that many TKIs can induce hypothyroidism and hyperthyroidism. In this study, the various molecules implicated in thyroid dysfunctions are analysed and the latest data on physiopathological mechanisms are approached in order to propose a strategy of thyroid monitoring of patients on TKI therapy. © 2014 European Society of Endocrinology Printed in Great Britain.


Freidja M.L.,UniversitedAngers | Tarhouni K.,UniversitedAngers | Toutain B.,UniversitedAngers | Fassot C.,UniversitedAngers | And 2 more authors.
Diabetes | Year: 2012

Flow-mediated remodeling of resistance arteries is essential for revascularization in ischemic diseases, but this is impaired in diabetes. We hypothesized that breaking advanced glycation end product (AGE) cross-links could improve remodeling in mesenteric resistance arteries in Zucker diabetic fatty (ZDF) rats compared with lean Zucker (LZ) rats. Arteries, exposed to high (HF) or normal (NF) blood flow after alternate arterial ligation in vivo, were collected after 2 weeks. In LZ rats, HF artery diameter was larger than for NF vessels, but this was not the case in ZDF rats. Endothelium-mediated dilation in ZDF rats, which was lower than in LZ rats, was further decreased in HF arteries. Treatment of rats with the AGE-breaker 4,5-dimethyl-3- phenacylthiazolium chloride (ALT-711) (3 mg/kg/day; 3 weeks) reversed diabetes-induced impairment of HF-dependent remodeling. ALT-711 also improved endothelium nitric oxide-dependent relaxation in mesenteric resistance arteries. Reactive oxygen species reduction restored relaxation in ZDF rats but not in LZ or ALT-711-treated rats. AGEs were reduced in ALT-711-treated ZDF rats compared with ZDF rats. Metalloproteinase activity, necessary for HF-dependent remodeling, was reduced in ZDF rats compared with LZ rats and restored by ALT-711. Thus, targeting AGE cross-links may provide a therapeutic potential for overcoming microvascular complications in ischemic disorders occurring in diabetes. © 2012 by the American Diabetes Association.

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