Role of mTOR, Bad, and Survivin in RasGAP Fragment N-Mediated Cell Protection.

Partial cleavage of p120 RasGAP by caspase-3 in stressed cells generates an N-terminal fragment, called fragment N, which activates an anti-apoptotic Akt-dependent survival response. Akt regulates several effectors but which of these mediate fragment N-dependent cell protection has not been defined yet. Here we have investigated the role of mTORC1, Bad, and survivin in the capacity of fragment N to protect cells from apoptosis. Neither rapamycin, an inhibitor of mTORC1, nor silencing of raptor, a subunit of the mTORC1 complex, altered the ability of fragment N from inhibiting cisplatin- and Fas ligand-induced death. Cells lacking Bad, despite displaying a stronger resistance to apoptosis, were still protected by fragment N against cisplatin-induced death. Fragment N was also able to protect cells from Fas ligand-induced death in conditions where Bad plays no role in apoptosis regulation. Fragment N expression in cells did neither modulate survivin mRNA nor its protein expression. Moreover, the expression of cytoplasmic survivin, known to exert anti-apoptotic actions in cells, still occurred in UV-B-irradiated epidermis of mouse expressing a caspase-3-resistant RasGAP mutant that cannot produce fragment N. Additionally, survivin function in cell cycle progression was not affected by fragment N. These results indicate that, taken individually, mTOR, Bad, or Survivin are not required for fragment N to protect cells from cell death. We conclude that downstream targets of Akt other than mTORC1, Bad, or survivin mediate fragment N-induced protection or that several Akt effectors can compensate for each other to induce the pro-survival fragment N-dependent response.

Tissue transglutaminase (TG2) acting as G protein protects hepatocytes against Fas-mediated cell death in mice.

Tissue transglutaminase (TG2) is a protein cross-linking enzyme known to be expressed by hepatocytes and to be induced during the in vivo hepatic apoptosis program. TG2 is also a G protein that mediates intracellular signaling by the alpha-1b-adrenergic receptor (AR) in liver cells. Fas/Fas ligand interaction plays a crucial role in various liver diseases, and administration of agonistic anti-Fas antibodies to mice causes both disseminated endothelial cell apoptosis and fulminant hepatic failure. Here we report that an intraperitoneal dose of anti-Fas antibodies, which is sublethal for wild-type mice, kills all the TG2 knock-out mice within 20 hours. Although TG2-/- thymocytes exposed to anti-Fas antibodies die at the same rate as wild-type mice, TG2-/- hepatocytes show increased sensitivity toward anti-Fas treatment both in vivo and in vitro, with no change in their cell surface expression of Fas, levels of FLIP(L) (FLICE-inhibitory protein), or the rate of I-kappaBalpha degradation, but a decrease in the Bcl-xL expression. We provide evidence that this is the consequence of the impaired AR signaling that normally regulates the levels of Bcl-xL in the liver. In conclusion, our data suggest the involvement of adrenergic signaling pathways in the hepatic regeneration program, in which Fas ligand-induced hepatocyte proliferation with a simultaneous inhibition of the Fas-death pathway plays a determinant role.

Selective accumulation of mature DC-Lamp+ dendritic cells in tumor sites is associated with efficient T-cell-mediated antitumor response and control of metastatic dissemination in melanoma.

The clinical relevance of dendritic cells (DCs) at the tumor site remains a matter of debate concerning their role in the generation of effective antitumor immunity in human cancers. We performed a comprehensive immunohistochemical analysis using a panel of DC-specific antibodies on regressing tumor lesions and sentinel lymph nodes (SLNs) in melanoma patients. Here we show in a case report involving spontaneous regression of metastatic melanoma that the accumulation of DC-Lamp+ DCs, clustered with tumor cells and lymphocytes, is associated with local expansion of antigen-specific memory effector CTLs. These findings were extended in a series of 19 melanoma-positive SLNs and demonstrated a significant correlation between the density of DC-Lamp+ DC infiltrates in SLNs with the absence of metastasis in downstream lymph nodes. This study, albeit performed in a limited series of patients, points to a pivotal role of mature DCs in the local expansion of efficient antitumor T-cell-mediated immune responses at the initial sites of metastasis and may have important implications regarding the prognosis, staging, and immunotherapy of melanoma patients.

ATP release due to Thy-1-integrin binding induces P2X7-mediated calcium entry required for focal adhesion formation.

Thy-1, an abundant mammalian glycoprotein, interacts with αvβ3 integrin and syndecan-4 in astrocytes and thus triggers signaling events that involve RhoA and its effector p160ROCK, thereby increasing astrocyte adhesion to the extracellular matrix. The signaling cascade includes calcium-dependent activation of protein kinase Cα upstream of Rho; however, what causes the intracellular calcium transients required to promote adhesion remains unclear. Purinergic P2X7 receptors are important for astrocyte function and form large non-selective cation pores upon binding to their ligand, ATP. Thus, we evaluated whether the intracellular calcium required for Thy-1-induced cell adhesion stems from influx mediated by ATP-activated P2X7 receptors. Results show that adhesion induced by the fusion protein Thy-1-Fc was preceded by both ATP release and sustained intracellular calcium elevation. Elimination of extracellular ATP with Apyrase, chelation of extracellular calcium with EGTA, or inhibition of P2X7 with oxidized ATP, all individually blocked intracellular calcium increase and Thy-1-stimulated adhesion. Moreover, Thy-1 mutated in the integrin-binding site did not trigger ATP release, and silencing of P2X7 with specific siRNA blocked Thy-1-induced adhesion. This study is the first to demonstrate a functional link between αvβ3 integrin and P2X7 receptors, and to reveal an important, hitherto unanticipated, role for P2X7 in calcium-dependent signaling required for Thy-1-stimulated astrocyte adhesion.

Small RNAs in bacterialcell-cell communication

When all three separate quorum-sensing signals act in concert in Vibrio harveyi, they maximize bioluminescence and fully repress type III secretion. V. harveyi has five qrr loci encoding small RNA regulatory molecules, each consisting of about 100 nucleotides; several of them are involved in repressing bioluminescence. Small RNAs also play roles in population density-dependent activities, including regulation of virulence factors, for bacterial pathogens such as Pseudomonas fluorescens, V. cholerae, Salmonella enterica, Pseudomonas aeruginosa, and Erwinia spp. Although some bacteria appear to carry redundant copies of small RNA genes with which to finely tune expression

Major: Electronics and Communication Engineering

Today, information technology is strategically important to the goals and aspirations of the business enterprises, government and high-level education institutions – university. Universities are facing new challenges with the emerging global economy characterized by the importance of providing faster communication services and improving the productivity and effectiveness of individuals. New challenges such as provides an information network that supports the demands and diversification of university issues. A new network architecture, which is a set of design principles for build a network, is one of the pillar bases. It is the cornerstone that enables the university’s faculty, researchers, students, administrators, and staff to discover, learn, reach out, and serve society. This thesis focuses on the network architecture definitions and fundamental components. Three most important characteristics of high-quality architecture are that: it’s open network architecture; it’s service-oriented characteristics and is an IP network based on packets. There are four important components in the architecture, which are: Services and Network Management, Network Control, Core Switching and Edge Access. The theoretical contribution of this study is a reference model Architecture of University Campus Network that can be followed or adapted to build a robust yet flexible network that respond next generation requirements. The results found are relevant to provide an important complete reference guide to the process of building campus network which nowadays play a very important role. Respectively, the research gives university networks a structured modular model that is reliable, robust and can easily grow.

Sex-mediated herbivory by galling insects on Baccharis concinna (Asteraceae)

The interaction patterns between the dioecious shrub Baccharis concinna Barroso (Asteraceae) and its speciose galling insect community were studied in southeastern Brazil. Two hypotheses were tested in this study: "the differential reproduction and growth hypothesis" that predicts that male plants present fewer reproductive structures and are larger than female plants; and the 'sex-biased herbivory hypothesis' that predicts that male plants support a larger abundance of insect galls than female plants. Plants did not show sexual dimorphism in growth (= mean leaf number). However, male plants had longer shoots and a lower average number of inflorescences than female plants. These results corroborate the hypothesis that male plants grow more and reproduce less than female plants. No statistically significant difference was found in the number of galls between male and female plants, but a sex by environmental effect on gall number was detected. When each species of galling insect was individually analyzed per population of the host plant, the rates of attack varied between sex and population of the host plant, and they were highly variable among the species of galling insects. These results highlight the importance of the interaction between sex and environment in the community structure of galling insects and indicate that other variables besides host sex may influence the patterns of attack by galling herbivores.

Pre-play communication and credibility: A test of Aumann's conjecture

The effectiveness of pre-play communication in achieving efficientoutcomes has long been a subject of controversy. In some environments,cheap talk may help to achieve coordination. However, Aumannconjectures that, in a variant of the Stag Hunt game, a signal forefficient play is not self-enforcing and concludes that an "agreementto play [the efficient outcome] conveys no information about what theplayers will do." Harsanyi and Selten (1988) cite this example as anillustration of risk-dominance vs. payoff-dominance. Farrell and Rabin(1996) agree with the logic, but suspect that cheap talk willnonetheless achieve efficiency. The conjecture is tested with one-waycommunication. When the sender first chooses a signal and then anaction, there is impressive coordination: a 94% probability for thepotentially efficient (but risky) play, given a signal for efficientplay. Without communication, efforts to achieve efficiency wereunsuccessful, as the proportion of B moves is only 35%. I also test ahypothesis that the order of the action and the signal affects theresults, finding that the decision order is indeed important. WhileAumann s conjecture is behaviorally disconfirmed when the signal isdetermined initially, the signal s credibility seems to be much moresuspect when the sender is known to have first chosen an action, andthe results are not statistically distinguishable from those whenthere is no signal. Some applications and issues in communication andcoordination are discussed.

RecA-mediated strand exchange traverses substitutional heterologies more easily than deletions or insertions.

RecA protein in bacteria and its eukaryotic homolog Rad51 protein are responsible for initiation of strand exchange between homologous DNA molecules. This process is crucial for homologous recombination, the repair of certain types of DNA damage and for the reinitiation of DNA replication on collapsed replication forks. We show here, using two different types of in vitro assays, that in the absence of ATP hydrolysis RecA-mediated strand exchange traverses small substitutional heterologies between the interacting DNAs, whereas small deletions or insertions block the ongoing strand exchange. We discuss evolutionary implications of RecA selectivity against insertions and deletions and propose a molecular mechanism by which RecA can exert this selectivity.

Mise en Place d’un Dispositif de Formation a Distance a l’universite du Cap-Vert« e-learning » :Les Technologies de L’information et de la Communication dans L’enseignement du Français Langue Etrangere

Ce mémoire est l’occasion de partager le résultat de la mise en place de ce dispositif de formation à distance que nous avons mené dans l’université du Cap-Vert. Dans la première partie, nous décrirons la nature de la politique éducative au Cap-Vert. Nous contextualiserons les principes de l’installation de l’université publique dans ce pays, ainsi que les intentions d’innovation pédagogique de cette université. La deuxième partie portera un regard complémentaire sur l’utilisation des TIC et de l’internet dans l’enseignement/apprentissage d’une langue, cas du français langue étrangère, et nous nous inspirerons des théories constructiviste et socio-constructiviste. Finalement, la troisième partie détaillera toutes les étapes de la conception et de la mise en place du dispositif de formation à distance. Dans cette troisième partie, nous aborderons dans un premier temps la question des enjeux et des risques du e-Learning et nous présenterons notre mission dans le projet « e-Learning.cv » mené par l’université. Puis, dans un deuxième temps nous analyserons quelques cours que nous avons mis en ligne, en sachant qu’un cours en ligne n’est pas la simple reproduction d’un support pédagogique imprimé mais il offre à l’apprenant un environnement multimédia et interactif. Finalement dans un troisième temps nous essayerons de prendre un peu de recul pour faire une analyse critique de ce que nous avons réalisé et essayer par là même de dégager les perspectives pour améliorer le travail effectué.