Showing papers in "M S-medecine Sciences in 2008"

Implication de la flore intestinale dans le métabolisme énergétique

Abstract: La flore intestinale est aujourd’hui consideree comme un organe a part entiere, qui joue un role cle dans le metabolisme energetique. La flore peut en effet augmenter la rentabilite energetique des aliments ingeres qui ont echappe a la digestion dans la partie haute de l’intestin, via leur fermentation. Par ailleurs, le flux des acides gras et leur stockage adipocytaire sont controles - notamment via le facteur FIAF (fastinginduced adipocyte factor), dont l’expression est tributaire de la presence de la flore intestinale. Des modifications de l’ecosysteme bacterien de l’intestin pourraient etre impliquees dans le developpement des alterations metaboliques liees au diabete de type 2 et a l’obesite. Des donnees experimentales demontrent qu’une alimentation hyperlipidique modifie la composition de la flore intestinale, en diminuant notamment les bifidobacteries, avec pour consequence une augmentation de l’absorption et des taux plasmatiques de lipopolysaccharide, qui participent a leur tour au declenchement et au developpement de l’inflammation, de l’insulino-resistance et du developpement de masse grasse. Reequilibrer ou modifier la composition de la flore intestinale pourrait constituer une voie therapeutique ou preventive susceptible de reduire l’impact d’une alimentation desequilibree sur le developpement du syndrome metabolique.

Voie alternative d’activation de NF-κB et cancer : Amis ou ennemis ?

Abstract: The family of NF-kappaB transcription factors plays a key role in diverse biological processes, such as inflammatory and immune responses, cell survival and tumor development. A new NF-kappaB activation pathway has been recently uncovered, the so-called alternative NF-kappaB activation pathway. It has been shown that this pathway mainly controls the activity of RelB, a member of the NF-kappaB family, and its activation requires IKKalpha, one of the two catalytic subunits of the IKK complex. Recent studies suggest that constitutive activation of the alternative pathway may be involved in tumor development, but most surprisingly it is also reported that IKKalpha exerts a protective function against uncontrolled cell proliferation and cancer development. This review discusses recent progresses in the understanding on how the alternative pathway may participate in cancer development, focusing more specifically on RelB and IKKalpha.

L’ampk : un lien entre métabolisme et reproduction ?

Abstract: 5'AMP-activated protein kinase (AMPK) is a serine/threonine kinase that acts as a fuel gauge in regulating energy metabolism. It restores cellular ATP levels by switching on catabolic pathways and switching off anabolic pathways. Some evidence indicates that AMPK could be also implicated in reproductive functions such as granulosa cell steroidogenesis and nuclear oocyte maturation in several species. Some metabolic hormones such as leptin, resistin, adiponectin (three adipokines) and ghrelin may in part act through the AMPK signaling. These hormones are also involved in the control of the reproductive functions at the hypothalamus-pituitary-gonadal axis level in both male and female. Thus, AMPK could be one of the signaling pathways controlling the interactions between energy balance and reproduction. The reproductive system is tightly coupled with energy balance, and thereby metabolic abnormalities can lead to the development of some physiopathological situations such as the polycystic ovary syndrome (PCOS). Women with PCOS show altered fertility mostly associated with metabolic disorders such as insulin-resistance, hyperinsulinemia and/or dyslipidemia. Metformin, an insulin-sensitizer, is used for the treatment of women with PCOS. It restores subnormal fertility and energy balance. Recent studies show that AMPK is involved in the mechanism of action of metformin. Thus, it may be a therapeutic target. However, further investigations are necessary to elucidate the functions of AMPK in both metabolic and reproductive tissues.

La dyskératose congénitale - Une maladie méconnue due à un maintien défectueux des télomères

Abstract: Dyskeratosis congenita (DC), also called Zinsser-Cole-Engman syndrome, is a rare, often fatal, inherited disease described for the first time at the dermatological level by Zinsser in 1906. It is a very polymorphous disease at the clinical level, with several modes of inheritance. Several clinical symptoms of the disease can appear after a latency period. These features render DC particularly difficult to diagnose. Mutations of several genes can cause DC, four of them having been identified so far. However, for a majority of patients, the affected gene has not been found. Remarkably, all identified genes (DKC1, hTERC, hTERT, and NOP10) encode components of telomerase, all required for telomere length maintenance. DC is thus a unique clinical model for the study of the roles of telomerase and telomeres. Moreover, proteins encoded by the DKC1 and NOP10 genes are also components of so-called box H/ACA RNPs required for ribosome synthesis and pre-mRNA processing. Alterations of these processes could contribute to the symptoms of DC patients carrying mutations in DKC1 or NOP10.

Les microalgues - Usines cellulaires productrices de molécules commerciales recombinantes

Abstract: Extraction of natural substances and chemical synthesis are the main sources of pharmaceutical molecules. When possible, one may transfer the gene of the molecule in living cells creating individual factories producing on demand and in a safe way the requested molecule. Today, bacteria, yeast, mammalian cells and plants constitute the main plate-forms for various commercial products. Microalgae present numerous advantages and could offer a powerful tool for the production of commercial molecules in a near future.

Les canaux TRP (transient receptor potential) - Une nouvelle famille de canaux à expression variée

Abstract: Transient receptor potential, TRP channels are a new superfamily of functionally versatile non-selective cation channels present from yeast to mammals. On the basis of their structural homology, TRP channels are subdivided in 7 groups : TRPC 1-7 Canonical, TRPV 1-6 Vanilloid, TRPM 1-8 Melastatin, TRPP 1-3 Polycystin, TRPML Mucolipin, TRPA Ankyrin and TRPN (NO mechanotransducer potential C), the latter not expressed in mammals. Their cloning and heterologous expression allowed to demonstrating that these channels are generally weakly voltage-dependent. They are activated by various ligands involving a signal transduction cascade as well as directly by multiple compounds, heat and pH. TRP channels are found in a broad range of cell types. TRP channels are essential in allowing animals to sense the outside world and cells to sense their local environment. Following mutations or anomalous behaviour, these channels have a major role in several human diseases.

Les cellules Th17 - Une nouvelle population de cellules T CD4 effectrices pro-inflammatoires

Abstract: After more than 20 years of hegemony, the Th1-Th2 paradigm was recently shaken by the discovery of a novel population of CD4 effector T cells, the Th17 cells. Th17 effector cells produce IL-17 and IL-22 and thus have pro-inflammatory properties notably favoring neutrophils recruitment and thus control of extracellular bacteria mainly at the epithelium surface. Th17 cells appear also as the major inducer of organ specific autoimmune pathologies such as EAE or rheumatoid arthritis, a function previously attributed to Th1 effector cells. The discovery of Th17 cells further supports the notion that effector CD4 T cells responses are diverse in vivo and that fine tuning of these different effector cells is critical to maintain tissue integrity.

Pathogénie du syndrome néphrotique à lesions glomérulaires minimes

Abstract: Idiopathic nephrotic syndrome is the most frequent glomerular disease in children. While genetic analyses have provided new insights into disease pathogenesis through the discovery of several podocyte genes mutated in distinct forms of inherited nephrotic syndrome, the molecular bases of minimal change nephrotic syndrome (MCNS) and focal and segmental glomerulosclerosis (FSGS) with relapse remain unclear. Although immune cell disorders, which may involve both innate and adaptive immunity, appear to play a role in the pathogenesis of steroid sensitive MCNS, the mechanisms by which they induce podocyte dysfunction remain unresolved. It was postulated that podocyte injury results from a circulating factor secreted by abnormal T cells, but the possibility that bipolarity of the disease results from a functional disorder shared by both cell systems is not excluded. MCNS relapses are associated with an activation of the immune system, including an expansion of T and B cell compartments and production of growth factors as well as many cytokines. Dysfunction of T cells is supported by three main findings: (1) inhibition of a type III hypersensitivity reaction ; (2) defects in immunoglobulin switch ; (3) unclassical T helper polarization resulting from transcriptional interference between Th1 and Th2 transcriptional factors.

Sexualité, prévention et rapports sociaux de sexe au fil de la vie

Abstract: Afin d'ameliorer les capacites de negociation des femmes en matiere de sexualite et de prevention, certains auteurs recommandent d'agir sur les representations sociales qui opposent une sexualite feminine fondee sur l'affectivite et la conjugalite et une sexualite masculine qui s'appuierait sur des besoins physiques. A partir de l'enquete Contexte de la sexualite en France (CSF), menee en 2006 aupres de 12 364 personnes, cet article propose une lecture biographique des trajectoires sexuelles et preventives et une analyse des dimensions normatives les plus structurantes. Les resultats attestent d'un rapprochement des pratiques sexuelles feminines et masculines mais egalement de la stabilite des representations differentialistes de la sexualite (qui attribuent a la nature les differences entre femmes et hommes). Revelatrices des inegalites sociales de sexe qui prevalent dans d'autres spheres, notamment professionnelles et familiales, ces representations generent des tensions qui rendent plus difficile pour les femmes l'adoption de pratiques preventives. L'enjeu revientalorsacreerlesconditionssocialesdel'egalite despratiques concretes entre les sexes dans les differentes spheres sociales.

Intérêt des lignanes dans la prévention et le traitement de cancers

Abstract: Lignans are diphenolic compounds widely distributed in the plant kingdom. They are mainly localised in lignified tissues, seeds and roots. These molecules are involved in plant defence mechanisms, but are also interesting for human health. Flax lignans belonging to the phytoestrogens are metabolised after ingestion into enterolignans that may offer a protection against the onset and development of hormono-dependant cancers. In vitro studies based on mammalian cellular models tend to confirm their beneficial effects observed during epidemiological studies and give us insights about their mechanisms of action. The most studied lignan, podophyllotoxin, and its semi-synthetic derivatives (etoposide, teniposide, etoposide phosphate), are particularly interesting at a curative level due to their cytotoxic properties. These semi-synthetic derivatives are used in chemotherapy of lung cancer for example. However, the extensive use of these anticancer drugs will lead to the problem of podophyllotoxin supply. This molecule is currently extracted from the rhizomes and roots of an Indian species Podophyllum hexandrum which has subsequently become endangered. Strategies are investigated to obtain economically viable alternative sources of Podophyllotoxin from plants and in vitro cultures of several species. Among them, north american Podophyllum peltatum, Linum wild species, Hyptis, Anthriscus, Juniperus or Dysosma species which accumulate Podophyllotoxin or closely related derivatives, are good candidates. double dagger.

L’histoire de la genèse de la loi Huriet-Sérusclat de décembre 1988 - Loi sur la protection des personnes qui se prêtent à des recherches biomédicales

Abstract: La genese de la loi du 20 decembre 1988 sur la protection des personnes qui se pretent a des recherches biomedicales est une histoire longue et complexe. Vingt-quatre ans s'ecouleront entre la Declaration d'Helsinki (1964) et la loi de 1988 avant que soit reconnu en France le besoin d'une protection specifique a menager aux patients ainsi qu'aux sujets sains lors de la mise en oeuvre d'une recherche biomedicale. La loi de 1988 a profondement modifie la pratique de la recherche medicale en France, mais, la encore, il a fallu du temps pour que ces modifications soient communement acceptees. Cette lente evolution des esprits des medecins et des juristes francais s'inscrit dans l'evolution de l'ethique medicale dans notre pays. Elle temoigne egalement de l'apparition de nouvelles exigences scientifiques et methodologiques pour l'evaluation des medicaments, de la modification profonde du statut de l'expert medical investigateur, des responsabilites des promoteurs et finalement de la reconnaissance des droits des personnes sujets d'experimentation.

Coup d’œil sur les petites GTPases Rho

Abstract: RhoA, Rac1, and Cdc42, the founding members of the Rho subfamily of small GTPases, have been the focus of many research studies since the first discovery of their primary roles in the reorganisation of the actin cytoskeleton. Since then, it is clear that they are involved in a great deal of cellular functions, including cell migration and adhesion, cell growth control, and membrane trafficking. The complete sequencing of the human genome has now highlighted a total of 20 genes encoding Rho-like proteins. Little is known about their distinct cellular functions, however, numerous studies are now beginning to unravel that each of the Rho GTPase must play a specific role in the cell in a timely and spatially regulated fashion. Here, we are presenting a brief overview of the distinct functional roles and similarities known to date for each of the Rho members.

Amiante et inflammation, rôle de l’inflammasome

Abstract: M/S n° 11, vol. 24, novembre 2008 > L’amiante comprend un ensemble de substances minerales (silicate de calcium ou de magnesium) de texture fibreuse dont la principale caracteristique est de resister au feu, et de posseder des proprietes isolantes. L’exposition repetee aux fibres d’amiante entraine communement une fibrose pulmonaire ou asbestose, ainsi que l’apparition de tumeurs specifiques de la plevre, du peritoine ou du pericarde, les mesotheliomes. Les mesotheliomes se developpent apres 30 a 40 ans d’exposition aux poussieres d’amiante. L’amiante favorise egalement l’apparition de tumeurs broncho-pulmonaires, deux a cinq fois plus frequentes que chez des personnes non exposees, apres seulement 10 a 20 ans d’exposition [1]. Des complications similaires sont liees a la silicose, declenchee par l’inhalation repetee des particules de silice. Dans les deux cas, asbestose et silicose, le developpement de la maladie se traduit par une etape initiale d’inflammation. Bien que de nombreuses etudes epidemiologiques aient demontre la relation causale entre l’amiante et l’apparition de fibroses pulmonaires et de mesotheliomes, les mecanismes biologiques aboutissant a l’inflammation pulmonaire apres exposition a l’amiante ou au silice sont a ce jour tres peu connus.

Phylogénie des SIV et des VIH - Mieux comprendre l’origine des VIH

Abstract: Emergence of human immunodeficiency viruses HIV-1 and HIV-2 results from interspecies transmission from simian viruses SIV. SIVcpzPtt infecting chimpanzees, and from which the HIV-1 (subgroups M and N) is derived is still found in the Pan troglodytes troglodytes population of south Cameroon chimpanzees. The ancestor of HIV-1 group O, is found in the Gorilla residing in Western Africa, but chimpanzees are in fact the initial reservoir of the SIV viruses SIVgor, and it is still unclear whether the group O HIV-1 has been transmitted to humans by gorillas and/or chimpanzees. At least eight interspecies transmissions between and humans implicating SIVsmm (from sooty mangabey monkeys) have occurred, corresponding to the eight VIH-2 groups. Since habits of hunting and meat preparation in the bush still persistently expose humans in Africa to SIV infection, new interspecies transmission of these viruses remains a possibility.

Les associations de parents d’enfants autistes - De nouvelles orientations

Abstract: Si dans les annees 1970 les associations de parents d'enfants autistes reclamaient l'ouverture d'hopitaux de jour, dans les annees 1990, cette revendication s'est transformee en une remise en cause des professionnels et une volonte de s'eloigner du milieu psychiatrique. Longtemps mises en accusation, les familles se montrent de plus en plus sceptiques vis-a-vis des autorites medicales et administratives et rejettent parfois les prises en charge proposees par les institutions. Elles reclament un diagnostic precoce pour obtenir des aides et mettre en place des interventions adaptees. La psychanalyse, qui pendant longtemps a constitue l'approche privilegiee en matiere d'autisme, est aujourd'hui decriee par les associations qui reclament l'integration scolaire pour leurs enfants et la generalisation des methodes educatives et comportementales.

[Transient brain ischemia: NMDA receptor modulation and delayed neuronal death].

Abstract: Transient global ischemia induces delayed neuronal death in certain cell types and brain regions while sparing cells in other areas. A key process through which oxygen-glucose deprivation triggers cell death is the excessive accumulation of the neurotransmitter glutamate leading to over excitation of neurons. In certain neurons this increase in glutamate will potentiate the NMDA type of glutamate receptor, which can then initiate cell death. This review provides an update of the neurophysiological, cellular and molecular mechanisms inducing post-ischemic plasticity of NMDA receptors, focusing on the sensitive CA1 pyramidal neurons in the hippocampus as compared to the relatively resistant neighboring CA3 neurons. Both a change in the equilibrium between protein tyrosine kinases/phosphatases and an increased density of surface NMDA receptors in response to ischemia may explain the selective vulnerability of specific cell types. Implications for the treatment of stroke and reasons for the failures of human clinical trials utilizing NMDA receptor antagonists are also discussed.

Profils de méthylation de l’ADN dans les cellules normales et cancéreuses

Abstract: In eukaryotes, the epigenetic mark DNA methylation is found exclusively at cytosine residues in the CpG islands of genes, transposons and intergenic DNA. Among functional roles, DNA methylation is essential for mammalian embryonic development, and is classically thought to function by stably silencing promoter activity. However, until recently, understanding of the distribution of cytosine methylation in the whole genome - and hence, identification of its targets - was very limited. High-throughput methodologies, including methylated DNA immunoprecipitation, have recently revealed genome-wide mapping of DNA methylation, and provided new and unexpected data. Clearly DNA methylation is selectively associated with some key promoters- and is not a prerequisite for promoter inactivation, since strong CpG island promoters are mostly unmethylated, even when inactive. Most germline-specific genes are methylated and permanently silenced in somatic cells, suggesting a role of this mark in maintaining somatic cellular identity. These large scale studies will also help understanding the deregulation of DNA methylation associated with cancer, among which unmethylation of germinal cells genes, and recent observtion of large hypomethylated regions in tumoral specimens. The next challenge will be to understand if these methylation changes occur randomly, or more likely are specified by oncogenes or linked to environmental pressure.

Asymétrie des génomes parentaux - Implications en pathologie

Abstract: At the time of fertilisation, the parental genomes have a strikingly different organisation. Sperm DNA is packaged globally with protamines, whereas the oocyte's genome is wrapped around nucleosomes. The maternal and paternal genomes are functionally different as well, and are both required for normal uterine and postnatal development. The functional requirement of both parental genomes is a consequence of differential epigenetic marking by DNA methylation during oogenesis and spermatogenesis, on a group of genes called imprinted genes. After fertilisation, these parental marks persist throughout development and convey the allelic expression of imprinted genes. Pathological perturbation of methylation imprints, before fertilisation in the germ cells, or during development, gives rise to growth-related syndromes, and is frequently observed in cancer as well. Alteration of imprints is thought to occur early in carcinogenesis and shows similarities with the acquisition of aberrant DNA methylation at tumour suppressor genes. This suggests that similar underlying mechanisms could be involved.

Micro-ARN : oncogènes et suppresseurs de tumeurs

Abstract: Les micro-ARN representent une decouverte majeure dans le domaine de la regulation de l’expression des genes. Ils participent a la regulation de l’expression de proteines en inhibant la traduction et/ou en induisant la degradation de leurs ARNm correspondants. L’etude de leurs fonctions a revele leur role dans la proliferation cellulaire et le developpement chez les metazoaires. La recherche des alterations moleculaires en cause dans l’apparition de cancers a permis d’identifier ces molecules en tant que nouveaux acteurs de la transformation neoplasique. Ainsi, des micro-ARN presentant les caracteristiques d’oncogenes (miR-17-92 ) ou celles de suppresseur de tumeurs (let-7 ) ont ete decouverts ces dernieres annees.

Classification pronostique du cancer du sein et profils d’expression génique sur puces à ADN

Abstract: Clinical and pathological heterogeneity of breast cancer, partly responsible of therapeutic failures, reflects complex and combinatory molecular alterations until now poorly documented by classical investigation tools. Thorough molecular typing is crucial. The advent of DNA microarray-based gene expression profiling allowed consistent progresses in this direction. A novel molecular taxonomy of breast cancer has been defined, signatures that predict clinical outcome or therapeutic response have been identified, some of them being tested in ongoing prospective clinical trials. In this review, we present the main results and their potential clinical applications. We also discuss their current limits and future hopes in the therapeutic management of patients.

La RNase L, un acteur essentiel de la réponse cellulaire antivirale

Abstract: The 2-5A/RNase L pathway is one of the first cellular defences against viruses. RNase L is an unusual endoribonuclease which activity is strictly regulated by its binding to a small oligonucleotide, 2-5A. 2-5A itself is very unusual, consisting of a series of 5'- triphosphorylated oligoadenylates with 2'-5' bonds. But RNase L activity is not limited to viral RNA cleavage. RNase L plays a central role in innate immunity, apoptosis, cell growth and differentiation by regulating cellular RNA stability and expression. Default in its activity leads to increased susceptibility to virus infections and to tumor development. RNase L gene has been identified as HPC1 (Hereditary Prostate Cancer 1) gene. Study of RNase L variant R462Q in etiology of prostate cancer has led to the identification of the novel human retrovirus closely related to xenotropic murine leukemia viruses (MuLVs) and named XMRV;

La « synergie phages-antibiotiques » - Un enjeu pour la phagothérapie

Abstract: L’activité antibactérienne des phages : un regain d’intérêt Nous avons tous nos prédateurs... L’être humain, après avoir surmonté les dangers des gros prédateurs (tigres aux dents de sabre par exemple), est maintenant menacé par de minuscules prédateurs comme les bactéries pathogènes. Heureusement, les bactéries sont aussi victimes de prédateurs naturels puisque, comme tous les autres organismes vivants, elles peuvent être infectées par des virus. Ces virus de bactéries, les bactériophages ou phages, sont très spécifiques ; ils infectent en général une seule espèce de bactérie et même souvent seulement certaines souches de l’espèce [1, 2]. Presque toutes les espèces bactériennes peuvent être infectées par de nombreux phages différents. Au total, plus de 5 500 phages distincts ont été identifiés par microscopie électronique dans les laboratoires du monde entier [3]. Cependant, cet échantillon de phages ne représente qu’une infime fraction de leur vraie diversité. Ces types de virus sont ubiquitaires et sont les « entités biologiques » les plus abondantes de la biosphère ; leur nombre dépasse de 10 à 15 fois celui de leurs bactéries hôtes [4, 5]. Les phages ont été découverts au début du XXe siècle par Félix d’Hérelle [6], un microbiologiste franco-canadien ayant travaillé un certain temps à l’Institut Pasteur de Paris. Dès leur découverte, ils ont été utilisés pour combattre certaines infections bactériennes. La vague de « phagothérapie » s’est alors propagée dans la communauté médicale jusqu’à ce qu’elle soit rapidement supplantée par la découverte et l’utilisation des antibiotiques. La phagothérapie a cependant continué d’exister jusqu’à ce jour en ex-Union soviétique, en particulier en République de Géorgie, grâce à l’Institut George Eliava cofondé par d’Hérelle et Eliava dans les années 1920 [7]. Depuis l’émergence de bactéries pathogènes résistantes aux antibiotiques, les travaux soviétiques suscitent un vif intérêt dans le monde médical et scientifique ; des sociétés biotechnologiques, pharmaceutiques et agroalimentaires tentent d’exploiter commercialement l’activité antibactérienne des phages. Ce regain d’intérêt touche aussi bien la recherche fondamentale que les enjeux cliniques et se traduit par un nombre croissant de publications scientifiques et de colloques internationaux, tel celui de l’Institut Pasteur de Paris en novembre 2007 [8].

Le double jeu de l'épigénétique : Cible et acteur du cancer

Abstract: The processes that affect the activity of the genome in a heritable manner without changing its sequence are called epigenetic. Here we review the modes of epigenetic gene regulation, and describe their alterations in cancer. We show how these mechanisms are interdependent, and how they intersect with genetic mutations. We argue that epigenetic abnormalities can occur both as a cause, and as a consequence of cancer. Indeed, oncogenic transformation can deeply alter the epigenetic information contained in the pattern of DNA methylation or histone tail modification. Conversely, epigenetic dysfunctions can drive cellular transformation. We then touch on some practical consequences of the prominence of epigenetic alterations in cancer : increasing knowledge of this field has allowed the development of a new generation of diagnostic tools and therapeutic avenues. Finally we point out that epigenetic phenomena may act as sensors that link environmental conditions to cancer.

Hépatite E - De la transmission zoonotique du virus à l’évolution chronique de l’infection chez l’immunodéprimé

Abstract: Pendant longtemps consideree comme une hepatite virale aigue d'origine hydrique evoluant selon un mode epidemique dans les regions tropicales et subtropicales, l'hepatite E est de plus en plus frequemment identifiee dans les pays industrialises sous la forme de cas sporadiques survenant chez des sujets n'ayant jamais sejourne en region endemique. Le depistage genomique et la caracterisation des genotypes viraux ont permis de documenter deux particularites de cette infection : la transmission zoonotique du virus a partir d'un reservoir porcin et l'evolution chronique de l'infection chez les personnes immunodeprimees.

OPG/RANKL - Implication et cible thérapeutique dans l’ostéoporose

Abstract: Given the increasing risk of fractures with aging in western countries, there is a need for the development of safe and efficient anti-osteoporotic drugs for the prevention and treatment of osteoporosis. Recent studies have provided evidence for an essential role of RANKL (Receptor Activator of Nuclear Factor-kappa B Ligand) and its decoy receptor osteoprotegerin in the control of osteoclast differentiation and survival. Post-menopausal osteoporosis results from an imbalance between resorption and formation associated with decreased OPG/RANKL. Targeting the OPG/RANKL system may therefore have a beneficial impact in osteoporosis. Accordingly, the development of novel strategies targeting OPG/RANKL using anti-RANKL or therapeutic intervention proved to be efficient to reduce bone resorption and to prevent bone loss in postmenopausal osteoporosis. This opens the way for novel therapeutic strategies for correcting bone metabolism in various pathologic disorders characterized by increased bone remodelling and bone loss.

Survivine en cancérologie : Aspects moléculaires et applications thérapeutiques

Abstract: Decouverte il y a dix ans, Survivine orchestre a la fois le cycle et la mort cellulaire, deux fonctions particulierement deregulees dans les cellules cancereuses. Presente au cours du developpement embryonnaire, puis absente des tissus differencies adultes, Survivine est fortement exprimee dans la plupart des tumeurs. Sa capacite a interagir avec differents partenaires moleculaires et sa distribution subcellulaire commencent a etre mieux connues. Ses proprietes pro-oncogeniques multiples et sa valeur pronostique demontree dans divers cancers ont fait de Survivine une cible anti-tumorale particulierement attractive et les premiers essais cliniques semblent prometteurs.

Structure et dynamique de la particule cœur de nucléosome

Abstract: In eukaryotic cell, a few meters of DNA are compacted in nuclear compartment of a few microns This high level of compaction is an important way to regulate gene expression In the present paper, we present a description of the organization of DNA into its first level of compaction: the nucleosome core particle The structure of the nucleosome has been described at an atomic resolution more than 10 years ago, where DNA is wrapped around an octamer of histones Post-translational modifications affecting histone tails have been shown to regulate the chromatin degree of compaction and thus the gene expression and regulation The structure of the NCP is far from being frozen and is highly dynamic Remodeling factors can induce DNA sliding around the histones, DNA transaction processes such as transcription and replication

Contribution de la Régulation post-transcriptionnelle à l’émergence de maladies : L’enfance de L’ARE

Abstract: De nombreux ARN messagers (ARNm) portent dans leur region 3’ non codante une sequence riche en adenosines et uridines (ARE) qui constitue un element regulateur cle de leur expression. L’ARE dicte la duree de vie et/ou la traductibilite de l’ARN qui le porte, via son interaction avec des proteines specifiques, les AUBP, et des miARN. Il permet ainsi a la cellule de s’adapter a un changement environnemental en modulant de maniere coordonnee, rapide et transitoire, le niveau d’expression d’un certain nombre d’ARNm. Etant donne que la plupart des proteines impliquees dans la reponse au stress et les reponses immune et inflammatoire, la croissance et la proliferation cellulaire sont codees par des ARNm portant un ARE, toute alteration de l’ARE ou de l’expression des AUBP peut provoquer une synthese proteique anormale a l’origine du developpement de maladies.