Laboratoire Of Biochimie Et Of Biologie Moleculaire

Timezgana, Morocco

Laboratoire Of Biochimie Et Of Biologie Moleculaire

Timezgana, Morocco
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Zhao W.,Aix - Marseille University | Moest T.,Aix - Marseille University | Zhao Y.,Aix - Marseille University | Guilhon A.-A.,Aix - Marseille University | And 4 more authors.
Scientific Reports | Year: 2015

The virulence of Salmonella relies on the expression of effector proteins that the bacterium injects inside infected cells. Salmonella enters eukaryotic cells and resides in a vacuolar compartment on which a number of effector proteins such as SifA are found. SifA plays an essential role in Salmonella virulence. It is made of two distinct domains. The N-terminal domain of SifA interacts with the host protein SKIP. This interaction regulates vacuolar membrane dynamics. The C-terminal has a fold similar to other bacterial effector domains having a guanine nucleotide exchange factor activity. Although SifA interacts with RhoA, it does not stimulate the dissociation of GDP and the activation of this GTPase. Hence it remains unknown whether the C-terminal domain contributes to the function of SifA in virulence. We used a model of SKIP knockout mice to show that this protein mediates the host susceptibility to salmonellosis and to establish that SifA also contributes to Salmonella virulence independently of its interaction with SKIP. We establish that the C-terminal domain of SifA mediates this SKIP-independent contribution. Moreover, we show that the two domains of SifA are functionally linked and participate to the same signalling cascade that supports Salmonella virulence.

Molinier S.,Laboratoire Of Biochimie Et Of Biologie Moleculaire
European Journal of Clinical Nutrition | Year: 2017

Although the global benefits of gastrostomy have been proven in amyotrophic lateral sclerosis (ALS), the impact on biological parameters has not been explored yet. The aim of this preliminary work was to evaluate the modification of biological parameters in patients with ALS undergoing gastrostomy. We retrospectively collected clinical and biological data from 44 patients having undergone gastrostomy at three time points (T0, T1 and T2: before, at the time of and after gastrostomy). We examined the relationship between the biological parameters and disease progression. Variations of the concentrations of total cholesterol significantly differed before (T1–T0) vs those after gastrostomy (T2–T1; P=0.0044). The variations of total cholesterol and low-density lipoprotein cholesterol concentrations after gastrostomy were negatively associated with survival (P=0.0002). This study showed for the first time that patients with ALS fed quite exclusively by gastrostomy had decreased blood cholesterol after gastrostomy. We suggest that a restoration of normal lipid metabolism should be planned in patients with ALS.European Journal of Clinical Nutrition advance online publication, 19 April 2017; doi:10.1038/ejcn.2017.54. © 2017 Macmillan Publishers Limited, part of Springer Nature.

PubMed | Nouakchott Military Hospital, Service de Chirurgie Orthopedique, Laboratoire Of Biochimie Et Of Biologie Moleculaire and Center Hospitalier National Of Nouakchott
Type: | Journal: Case reports in genetics | Year: 2016

Osteoporosis-pseudoglioma (OPPG) syndrome is a very rare autosomal recessive disorder, caused by mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. It manifests by severe juvenile osteoporosis with congenital or infancy-onset visual loss. We describe a case of OPPG due to novel mutation in LRP5 gene, occurring in a female Mauritanian child. This 10-year-old female child was born blind, and after then multiple fragility fractures appeared. PCR amplification and sequencing revealed a novel homozygous nonsense mutation in exon 10 of the LRP5 gene (c.2270G>A; pTrP757()); this mutation leads to the production of a truncated protein containing 757 amino acids instead of 1615, located in the third -propeller domain of the LRP5 protein. Both parents were heterozygous for the mutation. This is the first case of the OPPG described in black Africans, which broadens the spectrum of LRP5 gene mutations in OPPG.

Diaw M.,Laboratoire Of Physiologie Et Explorations Fonctionnelles | Samb A.,Laboratoire Of Physiologie Et Explorations Fonctionnelles | Diop S.,Laboratoire dHematoimmunologie | Sall N.D.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | And 3 more authors.
British Journal of Sports Medicine | Year: 2014

The present study compared the changes in blood viscosity, hydration status, body temperature and heart rate between a group of sickle cell trait (SCT) carriers and a control (Cont) group before and after a soccer game performed in two conditions: one with water offered ad libitum (hydration condition; Hyd) and the other one without water (dehydration condition; Dehyd). Blood viscosity and haematocrit per blood viscosity ratio (HVR; an index of red blood cell oxygen transport effectiveness) were measured before and at the end of each game. Resting blood viscosity was greater in the SCT carriers than in the Cont group. The increase of blood viscosity over baseline at the end of the game in the Cont group was similar in the two conditions. In contrast, the change in blood viscosity occurring in SCT carriers during soccer games was dependant on the experimental condition: (1) in Dehyd condition, blood viscosity rose over baseline; (2) in Hyd condition, blood viscosity decreased below resting level reaching Cont values. The Cont group had higher HVR than SCT carriers at rest. HVR remained unchanged in the Cont group at the end of the games, whatever the experimental condition. Although HVR of SCT carriers decreased below baseline at the end of the game performed in Dehyd condition, it increased over resting level in Hyd condition reaching the values of the Cont group. Our study demonstrated that ad libitum hydration in exercising SCT carriers normalises the blood hyperviscosity.

Boudaya M.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Fredj S.H.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Haj R.B.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Khrouf M.,Center Ibn Zohr Tunis | And 3 more authors.
Annals of Human Biology | Year: 2012

Background: Congenital bilateral absence of vas deferens (CBAVD) is responsible for 26% of male infertility. It occurs in 95% of men with cystic fibrosis.This malformation is present in patients with a sterile obstructive azoospermia but without clinical evidence of cystic fibrosis. Molecular study of the cystic fibrosis transmembrane conductance regulator (CFTR) gene responsible for cystic fibrosis could show the relationship between this disease and bilateral absence of vas deferens.Patients and methods: The study involved 20 male patients aged between 2840 years, referred with suspected cystic fibrosis and in whom bilateral absence of vas deferens was confirmed by cyto-biochemical analyses and urogenital ultrasound. Molecular study of the CFTR gene was based on several techniques: DHPLC, DGGE and direct sequencing.Results: Thirteen patients had CFTR mutations: F508del, G542X, W1282X, E1104X, 711+1G → T, V201M (TG) m and IVS8-5T. These mutations were associated with polymorphisms: M470V and D1270N. Seven cases presented only polymorphisms.Conclusion: The different mutations found in this study were associated with polymorphisms which decrease the severity of the disease and delay its onset. Thus, bilateral agenesis of the vas deferens is classed as a form of cystic fibrosis with only genital expression. © 2012 Informa UK, Ltd.

Veyrat-Durebex C.,University of Tours | Veyrat-Durebex C.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Corcia P.,University of Tours | Dangoumau A.,University of Tours | And 9 more authors.
Molecular Neurobiology | Year: 2014

Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disorder, is fatal for most patients less than 3 years from when the first symptoms appear. The aetiologies for sporadic and most familial forms of ALS are unknown, but genetic factors are increasingly recognized as causal in a subset of patients. Studies of disease physiology suggest roles for oxidative stress, glutamate-mediated excitotoxicity or protein aggregation; how these pathways interact in the complex pathophysiology of ALS awaits elucidation. Cellular models are being used to examine disease mechanisms. Recent advances include the availability of expanded cell types, from neuronal or glial cell culture to motoneuron-astrocyte co-culture genetically or environmentally modified. Cell culture experiments confirmed the central role of glial cells in ALS. The recent adaptation of induced pluripotent stem cells (iPSC) for ALS modeling could allow a broader perspective and is expected to generate new hypotheses, related particularly to mechanisms underlying genetic factors. Cellular models have provided meaningful advances in the understanding of ALS, but, to date, complete characterization of in vitro models is only partially described. Consensus on methodological approaches, strategies for validation and techniques that allow rapid adaptation to new genetic or environmental influences is needed. In this article, we review the principal cellular models being employed in ALS and highlight their contribution to the understanding of disease mechanisms. We conclude with recommendations on means to enhance the robustness and generalizability of the different concepts for experimental ALS. © 2013 Springer Science+Business Media.

Hadj Fredj S.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Fattoum S.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Chabchoub A.,Clinique Alyssa | Messaoud T.,Laboratoire Of Biochimie Et Of Biologie Moleculaire
Annals of Human Biology | Year: 2011

Background: There are few data on the molecular basis of Cystic Fibrosis (CF) in North Africa, probably due to under-diagnosis. Aim: This is the first study of cystic fibrosis transmembrane conductance regulator (CFTR) mutations in the Libyan population. Subjects and methods: This study analysed the complete coding region and flanking intronic sequences of the CFTR gene in 10 unrelated Libyan CF patients. Results: This study identified four mutations (F508del, c.1670delC, N1303K and E1104X), with a high frequency of the latter. Conclusion: Identification of CF mutations facilitates molecular investigation of cystic fibrosis in the Libyan population and helps to provide effective genetic counselling among CF families. © Informa UK, Ltd.

PubMed | Mahidol University, Laboratoire Of Biochimie Et Of Biologie Moleculaire, Chiang Mai University and University of Lyon
Type: Journal Article | Journal: International journal of biological macromolecules | Year: 2016

Ribosome biogenesis is the process of synthesis of the cellular ribosomes which mediate protein translation. Integral with the ribosomes are four cytoplasmic ribosomal RNAs (rRNAs) which show extensive post-transcriptional modifications including 2-O-methylation and pseudouridylation. Several hereditary hematologic diseases including Diamond-Blackfan anemia have been shown to be associated with defects in ribosome biogenesis. Thalassemia is the most important hematologic inherited genetic disease worldwide, and this study examined the post-transcriptional ribose methylation status of three specific active sites of the 28S rRNA molecule at positions 1858, 4197 and 4506 of -thalassemia trait carriers and normal controls. Samples from whole blood and cultured erythroid cells were examined. Results showed that site 4506 was hypermethylated in -thalassemia trait carriers in both cohorts. Expression of fibrillarin, the ribosomal RNA methyltransferase as well as snoRNAs were additionally quantified by RT-qPCR and evidence of dysregulation was seen. Hemoglobin E trait carriers also showed evidence of dysregulation. These results provide the first evidence that ribosome biogenesis is dysregulated in -thalassemia trait carriers.

Lassoued A.B.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Beaufils N.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Dales J.-P.,Laboratoire dAnatomie cytologie Pathologique | Gabert J.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Gabert J.,French Institute of Health and Medical Research
Expert Opinion on Medical Diagnostics | Year: 2013

Introduction: Hypoxia-inducible factor-1α (HIF-1α) is a key player in the signaling pathway that mediates a complex and pleiotropic range of adaptive responses to hypoxia. It serves as cellular hypoxia sensor and plays a critical role in physiologic processes including glucose metabolism, iron metabolism, erythropoiesis, angiogenesis, cell survival and apoptosis, but also, pathologic processes such as carcinogenesis, progression and metastasis of many cancers. With the recent advent of new molecular targeted therapies, there is a growing need of molecular understanding of physiology and physiopathology and increased demand of diagnosis, prognosis and follow-up markers. Areas covered: This paper reviews the biology of regulation of HIF-1α, its physiological and physiopathological effects. Expert opinion: The authors discuss the potential diagnosis and the prognosis significance of HIF-1α that was evaluated in recent studies. © 2013 Informa UK, Ltd.

Ben Lassoued A.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Nivaggioni V.,Laboratoire dHematologie | Gabert J.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Gabert J.,French Institute of Health and Medical Research
Expert Review of Molecular Diagnostics | Year: 2014

Minimal residual disease (MRD) assays are of a great value to assess treatment efficacy and may provide prognostic information. This is particularly relevant in the era of targeted therapy where the introduction of MRD monitoring has fundamentally transformed the way in which cancer patients are managed. While MRD guidelines are well-established for chronic myeloid leukemia, acute promyelocytic leukemia and acute lymphoblastic leukemia, areas for continuing development are available. High level of standardization and regular external quality control rounds and recommendations for data interpretation remain essential to improve MRD monitoring. In this review, we describe the different applications of MRD assays in most frequent hematologic malignancies and solid cancer and provide an overview of the strengths and potential weaknesses of each method. © 2014 Informa UK, Ltd.

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