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Matrix metalloproteinase-2 and -9 secretion by the human JAR choriocarcinoma cell line is stimulated by TNF-α  [PDF]
Benot Chénais
Advances in Bioscience and Biotechnology (ABB) , 2012, DOI: 10.4236/abb.2012.31009
Abstract: The JAR choriocarcinoma cell line share many of the characteristics of early placental trophoblast cells including the invasion properties. Matrix metallo-proteinases (MMPs), the main actors of matrix proteolysis, are involved in normal invasion as well as in the invasive character of tumor cells and the metastase formation. Tumor necrosis factor-α (TNF-α) is present in the placental environment and TNF-α levels are elevated in some placental pathologies. In the present work, we addressed whether TNF-α is a modulator of JAR cell MMP secretion. Following TNF-α stimulation, zymographic analysis showed the increased secretion of the active form of MMP-2 and to a lesser extent proMMP-2 and MMP-9. In addition, MMP-2 gene expression only increased slightly whereas MMP-9 and TIMP-1 transcripts were undetectable. This suggests that TNF-α may modulate the secretion of MMPs independently of MMP gene expression control.
Vectors for gene therapy: A place for DNA transposon  [PDF]
Benot Chénais
Open Journal of Genetics (OJGen) , 2013, DOI: 10.4236/ojgen.2013.32A1001
Abstract:

Gene therapy offers important perspectives in current and future medicine but suffers from imperfect vectors for the delivery of the therapeutic gene. Most preclinical and clinical trials have been based on the use of viral vectors, which have evident advantages but also some serious disadvantages. In the past decade the use of DNA transposon-based systems for gene delivery has emerged as a non-viral alternative. DNA transposon vector engineering remains largely in a preclinical phase but some interesting results have been obtained. This mini-review aims to provide the current state of the art on DNA transposon vectors used in a gene therapy perspective.

Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning.
Guillemette Benot,Bataille Alain R,Gévry Nicolas,Adam Maryse
PLOS Biology , 2005,
Abstract: H2A.Z is an evolutionary conserved histone variant involved in transcriptional regulation, antisilencing, silencing, and genome stability. The mechanism(s) by which H2A.Z regulates these various biological functions remains poorly defined, in part due to the lack of knowledge regarding its physical location along chromosomes and the bearing it has in regulating chromatin structure. Here we mapped H2A.Z across the yeast genome at an approximately 300-bp resolution, using chromatin immunoprecipitation combined with tiling microarrays. We have identified 4,862 small regions--typically one or two nucleosomes wide--decorated with H2A.Z. Those "Z loci" are predominantly found within specific nucleosomes in the promoter of inactive genes all across the genome. Furthermore, we have shown that H2A.Z can regulate nucleosome positioning at the GAL1 promoter. Within HZAD domains, the regions where H2A.Z shows an antisilencing function, H2A.Z is localized in a wider pattern, suggesting that the variant histone regulates a silencing and transcriptional activation via different mechanisms. Our data suggest that the incorporation of H2A.Z into specific promoter-bound nucleosomes configures chromatin structure to poise genes for transcriptional activation. The relevance of these findings to higher eukaryotes is discussed.
Variant Histone H2A.Z Is Globally Localized to the Promoters of Inactive Yeast Genes and Regulates Nucleosome Positioning
Benot Guillemette,Alain R. Bataille,Nicolas Gévry,Maryse Adam,Mathieu Blanchette,Fran?ois Robert,Luc Gaudreau
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0030384
Abstract: H2A.Z is an evolutionary conserved histone variant involved in transcriptional regulation, antisilencing, silencing, and genome stability. The mechanism(s) by which H2A.Z regulates these various biological functions remains poorly defined, in part due to the lack of knowledge regarding its physical location along chromosomes and the bearing it has in regulating chromatin structure. Here we mapped H2A.Z across the yeast genome at an approximately 300-bp resolution, using chromatin immunoprecipitation combined with tiling microarrays. We have identified 4,862 small regions—typically one or two nucleosomes wide—decorated with H2A.Z. Those “Z loci” are predominantly found within specific nucleosomes in the promoter of inactive genes all across the genome. Furthermore, we have shown that H2A.Z can regulate nucleosome positioning at the GAL1 promoter. Within HZAD domains, the regions where H2A.Z shows an antisilencing function, H2A.Z is localized in a wider pattern, suggesting that the variant histone regulates a silencing and transcriptional activation via different mechanisms. Our data suggest that the incorporation of H2A.Z into specific promoter-bound nucleosomes configures chromatin structure to poise genes for transcriptional activation. The relevance of these findings to higher eukaryotes is discussed.
Ixodes ricinus Tick Lipocalins: Identification, Cloning, Phylogenetic Analysis and Biochemical Characterization
Jér?me Beaufays, Benot Adam, Yves Decrem, Pierre-Paul Prév?t, Sébastien Santini, Robert Brasseur, Michel Brossard, Laurence Lins, Luc Vanhamme, Edmond Godfroid
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003941
Abstract: Background During their blood meal, ticks secrete a wide variety of proteins that interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. Methodology/Principal Findings Screening a cDNA library in association with RT-PCR and RACE methodologies allowed us to identify 14 new lipocalin genes in the salivary glands of the Ixodes ricinus hard tick. A computational in-depth structural analysis confirmed that LIRs belong to the lipocalin family. These proteins were called LIR for “Lipocalin from I. ricinus” and numbered from 1 to 14 (LIR1 to LIR14). According to their percentage identity/similarity, LIR proteins may be assigned to 6 distinct phylogenetic groups. The mature proteins have calculated pM and pI varying from 21.8 kDa to 37.2 kDa and from 4.45 to 9.57 respectively. In a western blot analysis, all recombinant LIRs appeared as a series of thin bands at 50–70 kDa, suggesting extensive glycosylation, which was experimentally confirmed by treatment with N-glycosidase F. In addition, the in vivo expression analysis of LIRs in I. ricinus, examined by RT-PCR, showed homogeneous expression profiles for certain phylogenetic groups and relatively heterogeneous profiles for other groups. Finally, we demonstrated that LIR6 codes for a protein that specifically binds leukotriene B4. Conclusions/Significance This work confirms that, regarding their biochemical properties, expression profile, and sequence signature, lipocalins in Ixodes hard tick genus, and more specifically in the Ixodes ricinus species, are segregated into distinct phylogenetic groups suggesting potential distinct function. This was particularly demonstrated by the ability of LIR6 to scavenge leukotriene B4. The other LIRs did not bind any of the ligands tested, such as 5-hydroxytryptamine, ADP, norepinephrine, platelet activating factor, prostaglandins D2 and E2, and finally leukotrienes B4 and C4.
Human Gamma Oscillations during Slow Wave Sleep
Mario Valderrama, Benot Crépon, Vicente Botella-Soler, Jacques Martinerie, Dominique Hasboun, Catalina Alvarado-Rojas, Michel Baulac, Claude Adam, Vincent Navarro, Michel Le Van Quyen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033477
Abstract: Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30–50 Hz) and high (60–120 Hz) frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves (“IN-phase” pattern), confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave (“ANTI-phase” pattern). This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks.
Variant Histone H2A.Z Is Globally Localized to the Promoters of Inactive Yeast Genes and Regulates Nucleosome Positioning
Benot Guillemette equal contributor,Alain R Bataille equal contributor,Nicolas Gévry,Maryse Adam,Mathieu Blanchette,Fran?ois Robert ,Luc Gaudreau
PLOS Biology , 2005, DOI: 10.1371/journal.pbio.0030384
Abstract: H2A.Z is an evolutionary conserved histone variant involved in transcriptional regulation, antisilencing, silencing, and genome stability. The mechanism(s) by which H2A.Z regulates these various biological functions remains poorly defined, in part due to the lack of knowledge regarding its physical location along chromosomes and the bearing it has in regulating chromatin structure. Here we mapped H2A.Z across the yeast genome at an approximately 300-bp resolution, using chromatin immunoprecipitation combined with tiling microarrays. We have identified 4,862 small regions—typically one or two nucleosomes wide—decorated with H2A.Z. Those “Z loci” are predominantly found within specific nucleosomes in the promoter of inactive genes all across the genome. Furthermore, we have shown that H2A.Z can regulate nucleosome positioning at the GAL1 promoter. Within HZAD domains, the regions where H2A.Z shows an antisilencing function, H2A.Z is localized in a wider pattern, suggesting that the variant histone regulates a silencing and transcriptional activation via different mechanisms. Our data suggest that the incorporation of H2A.Z into specific promoter-bound nucleosomes configures chromatin structure to poise genes for transcriptional activation. The relevance of these findings to higher eukaryotes is discussed.
A Model for Probabilistic Reasoning on Assume/Guarantee Contracts
Benot Delahaye,Benot Caillaud
Computer Science , 2008,
Abstract: In this paper, we present a probabilistic adaptation of an Assume/Guarantee contract formalism. For the sake of generality, we assume that the extended state machines used in the contracts and implementations define sets of runs on a given set of variables, that compose by intersection over the common variables. In order to enable probabilistic reasoning, we consider that the contracts dictate how certain input variables will behave, being either non-deterministic, or probabilistic; the introduction of probabilistic variables leading us to tune the notions of implementation, refinement and composition. As shown in the report, this probabilistic adaptation of the Assume/Guarantee contract theory preserves compositionality and therefore allows modular reliability analysis, either with a top-down or a bottom-up approach.
-Carleson Measures for a Class of Hardy-Orlicz Spaces
Benot Florent Sehba
International Journal of Mathematics and Mathematical Sciences , 2011, DOI: 10.1155/2011/926527
Abstract: An alternative interpretation of a family of weighted Carleson measures is used to characterize -Carleson measures for a class of Hardy-Orlicz spaces admitting a nice weak factorization. As an application, we provide with a characterization of symbols of bounded weighted composition operators and Cesàro-type integral operators from these Hardy-Orlicz spaces to some classical holomorphic function spaces. 1. Introduction Hardy-Orlicz spaces are the generalization of the usual Hardy spaces. We raise the question of characterizing those positive measures defined on the unit ball of such that these spaces embed continuously into the Lebesgue spaces . More precisely, let denote by the Lebesgue measure on and the normalized measure on the unit sphere which is the boundary of . denotes the space of holomorphic functions on . Let be continuous and nondecreasing function from onto itself. That is, is a growth function. The Hardy-Orlicz space is the space of function in such that the functions , defined by satisfy We denote the quantity on the left of the above inequality by or simply when there is no ambiguity. Let us remark that , where denotes the Luxembourg (quasi)-norm defined by Given two growth functions and , we consider the following question. For which positive measures on , the embedding map , is continuous? When and are power functions, such a question has been considered and completely answered in the unit disc and the unit ball in [1–6]. For more general convex growth functions, an attempt to solve the question appears in [7], in the setting of the unit disc where the authors provided with a necessary condition which is not always sufficient and a sufficient condition. The unit ball version of [7] is given in [8]. To be clear at this stage, let us first introduce some usual notations. For any and , let These are the higher dimension analogues of Carleson regions. We take as the power functions, that is, for . Thus, the question is now to characterize those positive measures on the unit ball such that there exists a constant such that We call such measures -Carleson measures for . We give a complete answer for a special class of Hardy-Orlicz spaces with , . For simplicity, we denote this space by . We prove the following result. Theorem 1.1. Let and . Then the following assertions are equivalent. (i)There exists a constant such that for any and , (i)There exists a constant such that To prove the above result, we combine weak-factorization results for Hardy-Orlicz spaces (see [9, 10]) and some equivalent characterizations of weighted Carleson measures
Bench-to-bedside review: Endothelial cell dysfunction in severe sepsis: a role in organ dysfunction?
Benot Vallet
Critical Care , 2002, DOI: 10.1186/cc1864
Abstract: The vascular endothelium regulates the flow of nutrient substances, diverse biologically active molecules and the blood cells themselves. This role of endothelium is achieved through the presence of membrane-bound receptors for numerous molecules, including proteins, lipid transporting particles, metabolites and hormones, as well as through specific junction proteins and receptors that govern cell–cell and cell–matrix interactions [1,2]. Endothelial dysfunction and/or injury with subendothelium exposure facilitates leucocyte and platelet aggregation, and aggravation of coagulopathy. Therefore, endothelium dysfunction and/or injury should favour impaired perfusion, tissue hypoxia and subsequent organ dysfunction.The present review describes, within the context of sepsis, why altered endothelial properties may be suspected to be involved in organ failure (Table 1).Endothelial injury describes a state in which microscopically visible endothelial cell (EC) shape change or injury can be identified, as well as defects in endothelial lining or elevated soluble markers of endothelial injury [3]. Anatomical damage to the endothelium during septic shock has been assessed in several studies [4,5,6]. A single injection of bacterial lipopolysaccharide (LPS) has long been demonstrated to be a nonmechanical technique for removing endothelium [5]. In endotoxic rabbits, observations tend to demonstrate that EC surface modification occurs easily and rapidly [5,6], with ECs being detached from the internal elastic lamina with an indication of subendothelial oedema. As early as 15 min after LPS injection [7] cellular injuries are apparent, with nuclear vacuolization, cytoplasmic swelling and protrusion, cytoplasmic fragmentation, and various degrees of detachment of the endothelium from its underlying layer. This can also be observed 10 hours after the onset of sepsis in a caecal ligation and puncture rat model [8]. Proinflammatory cytokines increase permeability of the Ecs, and this i
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