Institute Of Biologie Of Lille

Lille, France

Institute Of Biologie Of Lille

Lille, France
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Fabien S.,French Institute of Health and Medical Research | Olivier M.,Institute Of Biologie Of Lille | Khaldoun G.,French Institute of Health and Medical Research | Vivian V.,Unite de Biostatistique | And 6 more authors.
BioMed Research International | Year: 2014

The TRANSPEG study was a prospective study to assess the efficacy of antiviral therapy in patients with a recurrent hepatitis C virus (HCV) after liver transplantation. The influence of regulatory T-cells (Tregs) on the response to antiviral therapy was analyzed. Patients were considered as a function of their sustained virological response (SVR) at 18 months after treatment initiation. A transcriptomic analysis was performed to assess Treg markers (Tr1 and FoxP3+) in serum, PBMC, and liver biopsies. 100 patients had been included in the TRANSPEG study. Data from 27 of these patients were available. The results showed that the expression of CD49b (a predominant marker of Tr1) before the introduction of antiviral therapy was significantly associated with SVR. Responders displayed lower serum levels of CD49b than nonresponders (P < 0.02). These findings were confirmed in PBMC and liver biopsies even if in a nonsignificant manner for the limited number of samples. The assessment of CD49b levels is thus predictive of the response to antiviral therapy. This data suggests that CD49b may be a marker of the failure of the immune response and antiviral therapy during HCV recurrence. The assessment of CD49b could help to select patients who require earlier and more intensive antiviral therapy. © 2014 Stenard Fabien et al.


Moche H.,Institute Pasteur Of Lille | Moche H.,Servier Group | Moche H.,Lille 2 University of Health and Law | Chevalier D.,Lille 2 University of Health and Law | And 5 more authors.
Toxicological Sciences | Year: 2014

With the increasing human exposure to nanoparticles (NP), the evaluation of their genotoxic potential is of significant importance. However, relevance for NP of the routinely used in vitro genotoxicity assays is often questioned, and a nanoparticulate reference positive control would therefore constitute an important step to a better testing of NP, ensuring that test systems are really appropriate. In this study, we investigated the possibility of using tungsten carbide-cobalt (WC-Co) NP as reference positive control in in vitro genotoxicity assays, including 2 regulatory assays, the mouse lymphoma assay and the micronucleus assay, and in the Comet assay, recommended for the toxicological evaluation of nanomedicines by the French Agency of Human Health Products (Afssaps). Through these assays, we were able to study different genetic endpoints in 2 cell types commonly used in regulatory genotoxicity assays: the L5178Y mouse lymphoma cell line and primary cultures of human lymphocytes. Our results showed that the use of WC-Co NP as positive control in in vitro genotoxicity assays was conceivable, but that different parameters have to be considered, such as cell type and treatment schedule. L5178Y mouse lymphoma cells did not provide satisfactory results in the 3 performed tests. However, human lymphocytes were more sensitive to genotoxic effects induced by WC-Co NP, particularly after a 24-h treatment in the in vitro micronucleus assay and after a 4-h treatment in the in vitro Comet assay. Under such conditions, WC-Co could be used as a nanoparticulate reference positive control in these assays. © The Author 2013. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.


Freville A.,University of Lille Nord de France | Landrieu I.,Lille University of Science and Technology | Garcia-Gimeno M.A.,Institute Biomedicina Of Valencia Csic | Vicogne J.,Institute Of Biologie Of Lille | And 8 more authors.
Journal of Biological Chemistry | Year: 2012

Growing evidence indicates that the protein regulators governing protein phosphatase 1 (PP1) activity have crucial functions because their deletion drastically affects cell growth and division. PP1 has been found to be essential in Plasmodium falciparum, but little is known about its regulators. In this study, we have identified a homolog of Inhibitor-3 of PP1, named PfI3. NMR analysis shows that PfI3 belongs to the disordered protein family. High affinity interaction of PfI3 and PfPP1 is demonstrated in vitro using several methods, with an apparent dissociation constant K D of 100 nM. Wefurther show that the conserved 41KVVRW 45 motif is crucial for this interaction as the replacement of the Trp 45 by an Ala 45 severely decreases the binding to PfPP1. Surprisingly, PfI3 was unable to rescue a yeast strain deficient in I3 (Ypi1). This lack of functional orthology was supported as functional assays in vitro have revealed that PfI3, unlike yeast I3 and human I3, increases PfPP1 activity. Reverse genetic approaches suggest an essential role of PfI3 in the growth and/or survival of blood stage parasites because attempts to obtain knockout parasites were unsuccessful, although the locus of PfI3 is accessible. The main localization of a GFP-tagged PfI3 in the nucleus of all blood stage parasites is compatible with a regulatory role of PfI3 on the activity of nuclear PfPP1. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.


Lin T.,University of Texas Health Science Center at Houston | Gao L.,University of Texas Health Science Center at Houston | Zhang C.,University of Texas Health Science Center at Houston | Odeh E.,University of Texas Health Science Center at Houston | And 6 more authors.
PLoS ONE | Year: 2012

The identification of genes important in the pathogenesis of Lyme disease Borrelia has been hampered by exceedingly low transformation rates in low-passage, infectious organisms. Using the infectious, moderately transformable B. burgdorferi derivative 5A18NP1 and signature-tagged versions of the Himar1 transposon vector pGKT, we have constructed a defined transposon library for the efficient genome-wide investigation of genes required for wild-type pathogenesis, in vitro growth, physiology, morphology, and plasmid replication. To facilitate analysis, the insertion sites of 4,479 transposon mutants were determined by sequencing. The transposon insertions were widely distributed across the entire B. burgdorferi genome, with an average of 2.68 unique insertion sites per kb DNA. The 10 linear plasmids and 9 circular plasmids had insertions in 33 to 100 percent of their predicted genes. In contrast, only 35% of genes in the 910 kb linear chromosome had incapacitating insertions; therefore, the remaining 601 chromosomal genes may represent essential gene candidates. In initial signature-tagged mutagenesis (STM) analyses, 434 mutants were examined at multiple tissue sites for infectivity in mice using a semi-quantitative, Luminex-based DNA detection method. Examples of genes found to be important in mouse infectivity included those involved in motility, chemotaxis, the phosphoenolpyruvate phosphotransferase system, and other transporters, as well as putative plasmid maintenance genes. Availability of this ordered STM library and a high-throughput screening method is expected to lead to efficient assessment of the roles of B. burgdorferi genes in the infectious cycle and pathogenesis of Lyme disease. © 2012 Lin et al.


Steenackers A.,University of Lille Nord de France | Steenackers A.,Lille University of Science and Technology | Cazet A.,University of Lille Nord de France | Cazet A.,Lille University of Science and Technology | And 14 more authors.
Comptes Rendus Chimie | Year: 2012

B- and c-series of gangliosides are over-expressed in neuro-ectoderm- related cancers, including breast cancer. It has been shown that G D3 ganglioside is over-expressed in about 50% of invasive ductal breast carcinoma and the G D3 synthase (GD3S) gene displays higher expression among estrogen receptor (ER) negative breast tumors. We previously showed that GD3S expression in MDA-MB-231 breast cancer cells induces the expression of G D2 and increased cell proliferation and migration via a G D2-dependent activation of c-Met receptor. Here, we show that in ER-positive MCF-7 breast cancer cells, GD3S expression resulted in an increase of G D1b, which was associated with a decrease of G M1a and G M2. Meanwhile, GD3S expressing MCF-7 cells exhibited an increased migration without any modification of proliferation rate. Therefore, GD3S expression can result in different modifications of both ganglioside profiles and cell phenotypes depending on breast cell types. © 2011 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.


Lapierre F.,IEMN | Piret G.,University of Lille Nord de France | Drobecq H.,Institute Of Biologie Of Lille | Melnyk O.,Institute Of Biologie Of Lille | And 3 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2011

We present for the first time an electrowetting on dielectric (EWOD) microfluidic system coupled to a surface-assisted laser desorption-ionization (SALDI) silicon nanowire-based interface for mass spectrometry (MS) analysis of small biomolecules. Here, the transfer of analytes has been achieved on specific locations on the SALDI interface followed by their subsequent mass spectrometry analysis without the use of an organic matrix. To achieve this purpose, a device comprising a digital microfluidic system and a patterned superhydrophobic/superhydrophilic silicon nanowire interface was developed. The digital microfluidic system serves for the displacement of the droplets containing analytes, via an electrowetting actuation, inside the superhydrophilic patterns. The nanostructured silicon interface acts as an inorganic target for matrix-free laser desorption-ionization mass spectrometry analysis of the dried analytes. The proposed device can be easily used to realize several basic operations of a Lab-on-Chip such as analyte displacement and rinsing prior to MS analysis. We have demonstrated that the analysis of low molecular weight compounds (700 m/z) can be achieved with a very high sensitivity (down to 10 fmol μL-1). © 2011 The Royal Society of Chemistry.


Flajollet S.,European Genomic Institute for Diabetes EGID | Flajollet S.,French Institute of Health and Medical Research | Flajollet S.,Lille 2 University of Health and Law | Flajollet S.,Institute Pasteur Of Lille | And 9 more authors.
Hormone Molecular Biology and Clinical Investigation | Year: 2013

Vitamin A, ingested either as retinol or β-carotene from animal- or plant-derived foods respectively, is a nutrient essential for many biological functions such as embryonic development, vision, immune response, tissue remodeling, and metabolism. Its main active metabolite is all trans-retinoic acid (atRA), which regulates gene expression through the activation of α, β, and γ isotypes of the nuclear atRA receptor (RAR). More recently, retinol derivatives were also shown to control the RAR activity, enlightening the interplay between vitamin A metabolism and RAR-mediated transcriptional control. The white and brown adipose tissues regulate the energy homeostasis by providing dynamic fatty acid storing and oxidizing capacities to the organism, in connection with the other fatty acid-consuming tissues. This concerted interorgan response to fatty acid fluxes is orchestrated, in part, by the endocrine activity of the adipose tissue depots. The adipose tissues are also sites for synthesizing and storing vitamin A derivatives, which will act as hormonal cues or intracellularly to regulate essential aspects of adipocyte biology. As agents that prevent adipocyte differentiation hence, expected to decrease fat mass, and inducers of uncoupling protein expression, thus, favoring energy expenditure, retinoids have prompted many investigations to decipher their roles in adipose tissue pathophysiology, which are summarized in this review.


Hochart-Behra A.-C.,University of Lille Nord de France | Hochart-Behra A.-C.,Laboratoire Of Bacteriologie | Drobecq H.,University of Lille Nord de France | Drobecq H.,Institute Of Biologie Of Lille | And 6 more authors.
Anaerobe | Year: 2014

Bacteroides thetaiotaomicron maybe one of the most adaptable intestinal bacteria due to its complex genome. Known to be an opportunistic pathogenic anaerobe, B.thetaiotaomicron has recently been described as a symbiont with anti-inflammatory properties. In this study, peptide mass finger printing technique was used to identify the stress proteins (maybe anti-stress proteins for the host) extracted from B.thetaiotaomicron grown under nutrient starvation (without heme, blood or bile) prior to be placed in an aerobic solution containing a mild non-ionic detergent derived from cholic acid. We focus here on proteins related to stress, knowing that superoxide dismutase was previously identified in the extract. In parallel, the morphology of the bacterial cells was observed using electronic microscopy before and after the extraction process. The effective antioxidant effect of the extract was evaluated invitro against hydrogen peroxide. This work highlights the B.thetaiotaomicron ability to produce a large amount of stress proteins and to remain viable during the extraction. Budding vesicles were observed on its cell wall. The extraction process did not exceed 20h in order to preserve the bacterial viability that decreased significantly after 24h in preliminary studies. In our experimental conditions, an inhibitory effect of the extract was found against hydrogen peroxide. Animal models of inflammation will later check invivo if this extract of anti-stress proteins is able to counter the respiratory burst beginning an inflammation process. © 2014 Elsevier Ltd.


Dumas D.,University of Lorraine | Henrionnet C.,University of Lorraine | Hupont S.,University of Lorraine | Werkmeister E.,Institute Of Biologie Of Lille | And 3 more authors.
Bio-Medical Materials and Engineering | Year: 2010

We propose an innovative invasiveless technique in the field of nonlinear optical imaging to facilitate monitoring of cell/scaffold combinations for tissue repair. By using a near infrared (NIR) femtosecond excitation, we were able to introduce a new index based on decay time response for fluorescence (F) and Second Harmonic Generation (SHG) obtained with Time Correlated Single Photon Counting (TCSPC) microscopy to monitor structural information on the state of the matrix collagen. Some human Mesenchymal Stem Cells (hMSCs) seeded in 3D scaffolds were tested with different culture times (from D7 to D56) to analyze the effect of Tumor Growth Factor beta 1 (TGF-β1) on type-2 collagen expression in the matrix. After 14 days in the presence of TGF-β1, our results showed an increase in the expression of type-2 collagen synthesized by hMSCs, and a change in collagen conformation, as an indication of its ability to be detected as a harmonophore by TCSPC-SHG without the need for an exogenous probe. © 2010 IOS Press and the authors. All rights reserved.


PubMed | Unite de Biostatistique, French Institute of Health and Medical Research and Institute Of Biologie Of Lille
Type: | Journal: BioMed research international | Year: 2014

The TRANSPEG study was a prospective study to assess the efficacy of antiviral therapy in patients with a recurrent hepatitis C virus (HCV) after liver transplantation. The influence of regulatory T-cells (Tregs) on the response to antiviral therapy was analyzed. Patients were considered as a function of their sustained virological response (SVR) at 18 months after treatment initiation. A transcriptomic analysis was performed to assess Treg markers (Tr1 and FoxP3(+)) in serum, PBMC, and liver biopsies. 100 patients had been included in the TRANSPEG study. Data from 27 of these patients were available. The results showed that the expression of CD49b (a predominant marker of Tr1) before the introduction of antiviral therapy was significantly associated with SVR. Responders displayed lower serum levels of CD49b than nonresponders (P < 0.02). These findings were confirmed in PBMC and liver biopsies even if in a nonsignificant manner for the limited number of samples. The assessment of CD49b levels is thus predictive of the response to antiviral therapy. This data suggests that CD49b may be a marker of the failure of the immune response and antiviral therapy during HCV recurrence. The assessment of CD49b could help to select patients who require earlier and more intensive antiviral therapy.

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