Les recherches effectuées dans l’enseignement/apprentissage des langues vivantes et surtout dans le champ de la didactique des langues étrangères et secondes ont fait apparaître, depuis les années 20, des publics ayant des demandes spécifiques en communication professionnelle et fonctionnelle. Cette prise en compte des chercheurs a donné lieu à un domaine ouvert, varié, complexe, qui se caractérise par la grande diversité de ses contextes, situations d’enseignement, méthodes, objectifs, pratiques et dispositifs appelé le Français sur Objectifs Spécifiques. C’est dans le but de faire acquérir à ces publics des compétences culturelles et langagières spécifiques que, enseignants et chercheurs sont appelés aujourd’hui à se créer des démarches méthodologiques spécifiques. En s’inscrivant dans cette problématique, ce travail cherche à apporter des éléments de réponse aux demandes réelles des enseignants et des étudiants de français des universités angolaises plus particulièrement à celles de ceux de la faculté d’économie de l’université Agostinho Neto. L’objectif principal est donc, d’une part, d’identifier les besoins réels de ces derniers en prenant en compte les spécificités de leurs filières de formation et d’autre part, de concevoir, au cas par cas, des programmes et du matériel didactique permettant de développer chez les apprenants les compétences de compréhension et d’expression tant orales qu’écrites. Ces matériaux conçus à partir de documents authentiques à visée professionnelle oraux ou écrits sont susceptibles d’être directement utilisés en classe pour les enseignants qui voudront les transférer ou les réutiliser dans des situations similaires. / Research performed since the twenties in teaching/learning of the living languages, especially in the field of didactics of foreign and second languages, helped the rise of a certain audience with specific requests in professional and functional communication. This consideration of the researchers gave rise to an opened, varied, complex domain, which is composed of an important diversity of contexts, learning situations, methods, objectives, practices and structures of formation called "French for Specific Purposes". Teachers and researchers are brought today to create specific methodological approach, to help this audience gain specific cultural and linguistic skills. Within this problematic, this research aims at bringing elements of answer to the teachers and the french students of the Angolan universities, particularly to those of the Faculty of Economy of the Agostinho Neto University. Therefore, our purpose is to identify the real needs of the latter, taking into account peculiarities of their study paths and indeed to conceive programs and teaching tools, allowing them to develop oral and written comprehension and expression skills. These materials, made from “authentic oral or written documents with professional aim”, can be used directly in class by teachers who may want to reuse them in similar situations.

Cette thèse se propose de réfléchir à l’intégration d’une démarche interculturelle dans un enseignement-apprentissage de français juridique. Axé sur le public des étudiants étrangers venant suivre un cursus de droit en France, ce travail constitue une contribution à la didactique du français sur objectifs universitaires (FOU). Les questions didactiques abordées sont étayées par une mise en perspective sociolinguistique, historique et épistémologique approfondie : éclairer la manière dont s’articulent le « linguistique » et le « juridique » permet en effet de mieux comprendre la relative difficulté à concevoir un enseignement interculturel du français juridique. Pour (ré)introduire cette dimension interculturelle, il paraît pertinent de partir de certaines propositions herméneutiques existant en droit et en sciences du langage. L’herméneutique interculturelle développée dans ce travail vise à améliorer la préparation et l’accompagnement de l’insertion des étudiants juristes étrangers, en proposant une perspective véritablement relationniste. / This thesis explores the idea of integrating a cross-cultural approach into the teaching-learning process of legal French. Focused on the foreign student public who are studying Law in France, this work constitutes a contribution to French for Academic Purposes. The didactic questions raised here are backed up by a thorough “putting into perspective” of sociolinguistic, historic and epistemic factors : clarifying the manner in which “Linguistics” and “Law” are articulated to each other allows to better understand the relative difficulty of setting up a cross-cultural teaching program of legal French. In order to (re)introduce this cross-cultural dimension, it would seem appropriate to start with certain formerly-established hermeneutic propositions in Law and Language Sciences. The cross-cultural hermeneutics developed in this work aims at improving the preparation and accompaniment of foreign students’ integration, by proposing a truly relationist perspective.

Os carcinomas de cabeça e pescoço correspondem a 10% de todos dos tumores malignos, destes aproximadamente 40% se manifestam na boca e 90% correspondem ao carcinoma espinocelular. Os principais agentes carcinogênicos relacionados ao câncer bucal são o tabaco e o álcool. A cirurgia é o tratamento de eleição para o carcinoma de boca seguido dos tratamentos quimio e radioterápicos. O uso de lipossomas como vetor de quimioterápicos abre grandes perspectivas para o tratamento do câncer, pois possibilitam maior eficácia, reduzindo a toxicidade e a dosagem do fármaco. Neste projeto foram avaliados os efeitos pró apoptóticos \"in vitro\" da fosfoetanolamina sintética (FOS) e da sua formulação lipossomal DODAC/FOS em duas linhagens celulares de carcinoma espinocelular de língua humano, SCC-9 e SCC-25. A FOS, a formulação lipossomal DODAC/FOS e o carreador DODAC vazio apresentam diferentes significados em seu potencial citotóxico. A FOS aumentou significativamente a formação de lipoperóxidos pela membrana celular nas maiores concentrações estudadas. A análise das fases do ciclo celular mostrou aumento significativo da população de células com DNA fragmentado em ambas as linhagens celulares induzindo a morte celular por apoptose com aumento da expressão de Bad, Bax, citocromo c e diminuição de Bcl-2, como também alterou o potencial elétrico mitocondrial promovendo a ativação da caspase-3. A FOS e a formulação lipossomal DODAC/FOS induziram retração dos filamentos de actina e fragmentação do DNA. O conjunto de resultados mostra que o composto FOS e a sua formulação lipossomal DODAC/FOS atuam nos efeitos citotóxicos e antitumoral promovidos por estes alquilfosfoésteres, sendo capazes de induzir a morte celular por apoptose em diferentes apresentações / Head and neck carcinomas account for 10% of all malignant tumors, approximately 40% of these tumors manifest in the mouth and 90% correspond to squamous cell carcinoma. The main carcinogenic agents related to oral cancer are tobacco and alcohol. Surgery is the treatment of choice for oral carcinoma followed by chemo and radiotherapeutic treatments. The use of liposomes as a vector of chemotherapy offers great prospects for treatment of cancer, as they allow greater efficacy, reducing the toxicity and the dosage of drug. In this project, in vitro pro apoptotic effects of synthetic phosphoethanolamine (Pho-S) and DODAC/Pho-S liposomal formulation were evaluated in two human tongue squamous cell carcinoma cell lines, SCC-9 and SCC-25. Pho-S, DODAC/Pho-S liposomal formulation and the empty DODAC carrier have different meanings in their cytotoxic potential. Pho-S significantly increased the formation of lipoperoxides by cell membrane in higher concentrations studied. Analysis of the cell cycle phases showed a significant increase in the cell population with fragmented DNA in both cell lines inducing apoptosis cell death with increase expression of Bad, Bax, cytochrome c and decrease of Bcl-2, as well as altered the potential mitochondrial activation promoting caspase-3 activation. Pho-S and the DODAC/Pho-S liposomal formulation induced retraction of the actin filaments and DNA fragmentation. The set of results shows that the Pho-S compound and its liposomal formulation DODAC/Pho-S act on the cytotoxic and antitumor effects promoted by these alkylphosphoesters, being able to induce cell death by apoptosis in different presentations

Made available in DSpace on 2016-06-02T19:22:13Z (GMT). No. of bitstreams: 1 TeseRCV.pdf: 1865864 bytes, checksum: 07a6f9c430514b03de88b087935a28a4 (MD5) Previous issue date: 2005-07-06 / The lesion of central nucleus of amygdala (NCeA) decrease sodium intake, but not thirst, induced by angiotensin II and sodium depletion in furosemide model. In the present work we investigated the effect of lesion of NCeA on sodium intake induced by the water deprivation rehydration protocol (PHRP). Adult male Holtzman rats (260-320 g) housed for five days with water, 1.8% NaCl and regular food pellets received sham (n = 12) or eletrolytic lesion of NCeA (1 mA / 20 s): unilateral (n = 10) and bilateral (n = 8). The ingestion of water and 1.8% NaCl was recorded five days pre- and post-surgery. No significant alteration in daily water or sodium intake was produced after sham-lesion surgery. The uni- or bilateral lesions of NCeA reduced the daily 1.8% NaCl intake, but did not alter daily water intake. Seven days after surgery, water and 1.8% NaCl were removed and only food remained avaiable for 24 or 36 hours. Then, food was removed and water was offered for rehydration (2 hours), PHRP protocol. After partial rehydration with water, 1.8% NaCl and water was made avaiable and ingestion was recorded at 15, 30, 60 and 120 minutes (sodium appetite test). No significant alteration was observed in cumulative 1.8% NaCl or water at sodium appetite test in NCeA lesioned rats after PH24hRP. After PH36hRP, the bilateral lesion of NCeA reduced 1.8% NaCl intake for 3.4 + 1.7 ml/h compared with sham lesion (8.6 + 1.6 ml / h, p < 0.05). Water intake was not altered by NCeA lesion. There was an enhancement in need-induced 1.8% NaCl intake of intacts rats in response to repeated episodes of water deprivation. This enhancement occurred neither in the group with NCeA lesion nor in the group with sham lesion. The NCeA lesion also reduced the 1.8% NaCl intake induced by sodium depletion with furosemide and removal of ambient sodium, thus confirme the effects of amygdalar lesion already described in the literature. The integrity of NCeA is necessary for full expression of sodium appetite in the PHRP protocol. Water deprivation induced Fos expression in hypothalamics nuclei and cells groups of the lamina terminalis. Fos expression was reverted or did not change in different nuclei after rehydratation in PHRP protocol. We also investigated the effect of lesion in the NCeA on Fos expression in forebrain and pontine structures in response to 36 hours of water deprivation and subsequent rehydration that immediately precede Na+ intake. Rats (n = 6 per group), whith sham lesion (F) or bilateral lesion of NCeA, were submitted to to PH36hRP. Expression of Fos (as assessed by immunohistochemistry) in lamina terminalis or lateral parabrachial nucleus was not altered, but increased in medial parabrachial nucleus and parvocellular division of paraventricular nucleus of hypothalamus in NCeA lesioned rats. The increased neuronal activity in medial parabrachial nucleus may be related to the inibitory effect of NCeA lesion on sodium appetite. / A lesão do núcleo central da amígdala (NCeA) reduz o comportamento de ingestão de sódio, mas não a sede, induzido por angiotensina II e depleção de sódio no modelo de furosemida. No presente trabalho investigamos o efeito da lesão do NCeA na ingestão de sódio induzida no modelo de privação hídrica-reidratacão parcial (PHRP). Ratos Holtzman adultos (260-320 g) ambientados por cinco dias com água, NaCl 1,8% e ração foram submetidos a lesão fictícia (n=12) ou lesões eletrolíticas do NCeA (1 mA /20 s): unilateral (n = 10) e bilateral (n = 8). Foi medida a ingestão diária de água e NaCl 1,8% cinco dias antes e cinco dias após as lesões. A lesão fictícia não alterou a ingestão diária de água nem de NaCl 1,8%. Lesões uni- ou bilaterais do NCeA reduziram a ingestão diária de sódio e não alteraram a ingestão diária de água. Sete dias após as lesões, foram removidas a água e NaCl 1,8%, mas não a ração por 24 ou 36 horas. Então foi removida a ração e oferecida água por duas horas (modelo PHRP) e após a reidratação parcial, NaCl 1,8% e água foram oferecidos e medidos aos 15, 30, 60 e 120 minutos (teste do apetite ao sódio). Na privação hídrica de 24 horas, lesões do NCeA não alteraram a ingestão de NaCl 1,8% ou água no teste do apetite ao sódio após reidratação parcial, já na privação hídrica de 36 horas, a lesão bilateral do NCeA reduziu a ingestão de NaCl 1,8% para 3,4 + 1,7 ml / h em relação ao grupo com lesão fictícia (8,6 + 1,6 ml / h, p < 0,05), no teste do apetite após reidratação parcial. A ingestão de água não foi alterada pela lesão do NCeA. Houve incremento na ingestão regulatória de NaCl 1,8% em resposta a episódios repetidos de privações hídricas sucessivas em animais intactos. Este incremento não ocorreu em nenhum dos grupos com lesão do NCeA e nem mesmo no grupo com lesão fictícia. A lesão do NCeA reduziu também a ingestão de NaCl 1,8% induzida por depleção de sódio com furosemida e remoção de sódio ambiente, confirmando os efeitos da lesão amigdalar já descritos na literatura.. A integridade do NCeA é necessária para a expressão completa do apetite ao sódio no modelo PHRP em ratos, sendo importante para a ingestão regulatória de sódio. A privação hídrica induz expressão da proteína c-Fos em núcleos hipotalâmicos e estruturas da lâmina terminal. Essa expressão é revertida ou permanece inalterada em diferentes núcleos após reidratação no modelo PHRP. Este trabalho também investigou o efeito de lesões do NCeA na expressão do gene c-Fos em áreas prosencefálicas e pontinas em resposta a 36 horas de privação hídrica e subsequente reidratação que precede a ingestão de sódio. Ratos (n = 6 por grupo), com lesão fictícia (F) ou com lesão eletrolítica bilateral do NCeA (L), foram mantidos hidratados ou submetidos a privação hídrica e reidratação parcial, e tiveram os encéfalos perfundidos para detecção imunohistoquímica de neurônios expressando a proteína c-Fos. A expressão de c-Fos em estruturas da lâmina terminal, núcleo supra-óptico ou no núcleo parabraquial lateral não foi alterada e aumentou no núcleo parabraquial medial e porção parvocelular do núcleo paraventricular do hipotálamo em ratos com lesão bilateral do NCeA. A atividade neuronal aumentada no núcleo parabraquial medial pode estar relacionada ao efeito inibitório da lesão do NCeA no apetite ao sódio neste modelo.

Made available in DSpace on 2014-12-17T15:36:41Z (GMT). No. of bitstreams: 1 RuthnaldoRML_TESE.pdf: 6295823 bytes, checksum: 7a96da99950cb2a0427cd0d44be715d0 (MD5) Previous issue date: 2014-08-30 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The pregeniculate nucleus (PGN) of the primate s thalamus is an agglomerate neuronal having a cap shaped located dorsomedially to the main relay visual information to the cerebral cortex, the dorsal lateral geniculate nucleus (GLD). Several cytoarchitectonic, neurochemical and retinal projections studies have pointed PGN as a structure homologous to intergeniculate leaflet (IGL) of rodents. The IGL receives retinal terminals and appears to be involved in the integration of photic and non-photic information relaying them, through geniculo-hypothalamic tract (TGH), to the main circadian oscillator in mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus. Thus, the IGL participates in the control of the biological rhythm by modulating the activity of the SCN. Pharmacological and IGL injury studies conclude that it is critical in the processing of non-photic information which is transmitted to the SCN. Other studies have found that especially neurons immunoreactive to neuropeptide Y (NPY) respond to this type of stimulation, determined by its colocation with the FOS protein. Has not been determined if the PGN responds, expressing the FOS protein, to the non-photic stimulus nor the neurochemical nature of these cells. Thus, we apply a dark pulse in the specifics circadian phases and analyze the pattern of expression of FOS protein in PGN of the marmoset (Callithrix jacchus). We found that in all animals analyzed the FOS expression was higher in the experimental than in the control group. There was a higher expression of FOS when the dark pulse was applied during the subjective day between the groups. Still, a subregion of the PGN, known by immunoreactive to NPY, had a greater number of FOS-positive cells in relation to his other just close dorsal region. Our data corroborate the theory that the PGN and IGL are homologous structures that were anatomically modified during the evolutionary process, but kept its main neurochemical and functional characteristics. However, injury and hodological studies are still needed for a more accurate conclusion / O n?cleo pr?-geniculado (NPG) do t?lamo de primatas ? um aglomerado neuronal, em forma de capuz, localizado dorsomedialmente ao principal retransmissor de informa??es visuais para o c?rtex cerebral, o n?cleo geniculado lateral dorsal (GLD). Diversos estudos citoarquitet?nicos, neuroqu?micos e de proje??es retinianas t?m apontado o NPG como estrutura hom?loga ao folheto intergeniculado (FIG) de roedores. O FIG recebe terminais retinianos e parece estar envolvido na integra??o de informa??es f?ticas e n?o-f?ticas retransmitindo-as, atrav?s do trato geniculohipotal?mico (TGH), ao principal oscilador circadiano em mam?feros, o n?cleo supraquiasm?tico (NSQ) do hipot?lamo. Desse modo, o FIG participa no controle da ritmicidade biol?gica modulando a atividade do NSQ. Estudos farmacol?gicos e de les?o concluem que o FIG ? fundamental no processamento de informa??es n?of?ticas as quais s?o transmitidas ao NSQ. Outros trabalhos verificaram que, especialmente, neur?nios imunorreativos ao neuropept?deo Y (NPY) respondem a esse tipo de est?mulo, determinados por sua co-localiza??o com a prote?na FOS. Ainda n?o foi determinado se o NPG responde, expressando a prote?na FOS, a est?mulos n?o-f?ticos nem tampouco a natureza neuroqu?mica dessas c?lulas. Assim, aplicamos um pulso de escuro em fases circadianas espec?ficas e analisamos o padr?o de express?o da prote?na FOS no NPG do sagui (Callithrix jacchus). Verificamos que em todos os animais analisados a express?o de FOS foi maior em rela??o ao grupo controle. Houve uma maior express?o de FOS quando o pulso de escuro foi aplicado durante o dia subjetivo entre os grupos estudados. Ainda, uma sub-regi?o do NPG, sabidamente imunorreativa a NPY, apresentou um maior n?mero de c?lulas FOSpositivas em rela??o ? sua outra regi?o imediatamente mais dorsal. Os nossos dados corroboram com a teoria de que o NPG e o FIG s?o estruturas hom?logas que se modificaram anatomicamente durante o processo evolutivo, mas mantiveram suas principais caracter?sticas neuroqu?micas e funcionais. No entanto, estudos de les?o e hodol?gicos ainda s?o necess?rios para uma conclus?o mais precisa

To be successful in today&apos;s competitive market, service providers should look at user&apos;s satisfaction as a critical key. In order to gain a better understanding of customers&apos; expectations, a proper evaluations which considers intrinsic characteristics of perceived quality of service is needed. Due to the subjective nature of quality, the vagueness of human judgment and the uncertainty about the degree of users&apos; linguistic satisfaction, fuzziness is associated with quality of experience. Considering the capability of Fuzzy logic in dealing with imprecision and qualitative knowledge, it would be wise to apply it as a powerful mathematical tool for analyzing the quality of experience (QoE). This thesis proposes a fuzzy procedure to evaluate the quality of experience. In our proposed methodology, we provide a fuzzy relationship between QoE and Quality of Service (QoS) parameters. To identify this fuzzy relationship a new term called Fuzzi ed Opinion Score (FOS) representing a fuzzy quality scale is introduced. A fuzzy data mining method is applied to construct the required number of fuzzy sets. Then, the appropriate membership functions describing fuzzy sets are modeled and compared with each other. The proposed methodology will assist service providers for better decision-making and resource management.

Notre étude relève du domaine de la didactique des langues et plus particulièrement sur la focalisation sur l’utilisation des présentations PowerPoint pour les réalisations des tâches. Ces dernières jouent un rôle important dans le déclenchement de processus d’apprentissage. Lorsque les apprenants réalisent des tâches sur support PowerPoint,interagissent ensemble pour construire du sens, ils sont dotés d’un statut d’acteurs sociaux.Cette étude se donne alors comme objectif d’améliorer la pratique des apprenants en classe et de résoudre certaines de leurs difficultés didactiques et pédagogiques à travers un dispositif hybride. Celui-ci est fondé sur des macro-tâches réalisées majoritairement en semi distance et mise en place majoritairement en présentiel à travers des exposés techniques. Ces derniers ont été conçus pour encourager le développement de performances langagières attendues en production orale des apprenants.Elle se base sur une recherche-action qui a été menée en Ouganda pour des apprenants anglophones qui apprennent le français comme langue étrangère à Makerere UniversityBusiness School (MUBS) à Kampala. Cette étude a porté sur un exposé technique oral parles apprenants du Français sur Objectif Spécifique (FOS) à (MUBS) en Ouganda.Cette recherche-action vise à améliorer l’expression orale en FOS des apprenants de l’université MUBS. Nous avons donc menée des multiples expérimentations qui nous ont permises dans un premier temps de questionner l’impact d’un exposé oral des tâches réelles collectivement élaborée et présentée sur support Power Point sur la production orale de ces apprenants. Ces tâches avaient comme objectif d’encourager les apprenants de transformer un texte en titre, sous-titres et paragraphes, puis de présenter leur travail sous forme de diaporama avec PowerPoint. Le but était d’éviter la lecture linéaire de l’exposé,afin d’accroître leur confiance en eux-mêmes et dans l’interaction en FOS. Grâce à la recherche-action, nous avons pu définir précisément en quoi et pourquoi les choix de nos tâches, de nos activités devraient avoir un effet positif sur notre public cible. / The initial objective of this study, which lies within the field of language teaching andespecially on the role of information and Communication Technology (ICT), is to investigate the potential of ICT in triggering oral language development in the learners of French for Specific purposes (FSP) at Makerere University Business School. This studyadopts action research that focuses on the role of technologies deployed in oral technical presentations of macro-tasks such as the use of MS Office. The aim is to enhance Frenchlearners’ skills in French for Specific purposes. The social constructivist or cultural hypotheses posit that social interaction plays an important role in L2 acquisition (French in this case) in FSP classes through a hybrid environment based on macro-tasks performed indistance and presented in class.The current action research project involved identifying and putting into place a learningsystem for learners of FSP who experienced several difficulties with their spoken French inthe learning process. It further posits that learners construct the new language through socially mediated interaction. Subsequently, this involved establishing whether the use ofPowerPoint presentation (PPP) would engage learners of FSP in collective actions both inthe classroom and in the real world activities. In addition, there was an attempt to establishif relevant web quest materials were likely to enhance oral language acquisition and prompt learners to take responsibility for their own learning.

Les marsupiaux naissent très immatures, mais doivent atteindre une tétine, sans aide de la mère, à laquelle ils s’attachent pour poursuivre leur développement. Des informations sensorielles sont nécessaires pour s’orienter vers la tétine, la trouver, et s’y attacher. Le système vestibulaire, associé au sens de l’équilibre, a été proposé comme pouvant guider les petits marsupiaux vers la tétine en agissant sur les réseaux moteurs spinaux. Diverses études des marsupiaux suggèrent que le développement de ce système pourrait être suffisamment avancé pour influencer les comportements moteurs chez les nouveau-nés, mais son fonctionnement n’a jamais été testé. Pour le faire, nous avons soumis des opossums âgés de P0 (jour de la naissance; postnatal 0) à P21 à des stimulations vestibulaires et traité les tissus de la tête par immunohistochimie pour révéler c-Fos, utilisé comme indicateur d’activité neuronale. Du marquage dans les noyaux vestibulaires a été observé seulement à partir de P15. Pour confirmer ces résultats, nous avons effectué deux types d’expériences de stimulation sur des préparations in vitro d’opossums et enregistré les réponses motrices induites. Ainsi, des élévations de la tête n’ont pas permis de déceler de réponse suite aux stimulations aux âges étudiés (P4-P12). Par contraste, des pressions mécaniques directement appliquées sur le labyrinthe afin de stimuler les organes vestibulaires ont entrainé des réponses à tous les âges testés (P1-P9). Nos résultats suggèrent que la fonction du système vestibulaire est limitée par la maturité de ses organes sensoriels, et qu’il n’influence pas la motricité des nouveau-nés d’opossum en conditions physiologiques avant environ la fin de la 2e semaine de vie, même si les voies nerveuses entre les organes vestibulaires et la moelle épinière semblent déjà établies à la naissance. / Marsupials are born very immature, but must nevertheless find a teat, unaided by the mother, to which they attach to pursue their development. Sensory inputs are necessary to find the teat and attach to it, but the senses involved are still under discussion. The vestibular system, responsible for the sense of balance, was proposed as influencing motor behavior of newborns in various marsupial species by an action on spinal motor networks. Studies in the opossum Monodelphis domestica suggest that the development of the vestibular system could be advanced enough to influence locomotion at birth but its functionality has never been tested. To do that, we subjected intact opossums aged P0 (Postnatal day 0 ; day of birth) to P21 to vestibular stimulations and immunohistochemically processed their brain tissues to reveal c-Fos, used as a marker of neuronal activity. Immunoreactivity of neurons in the vestibular nuclei was observed only from P15 onwards. To confirm those results, we performed two series of experiments on in vitro preparations of newborn opossums, using stimulation of the vestibular apparatus and physiological recording of the induced motor responses Thus, vertical head tilts did not induce motor response at any of the ages studied (P4-P12). In contrast, mechanical pressure applied on the labyrinth to stimulate the vestibular organs induced motor responses at all ages studied (P1-P9). Our results suggest that the vestibular system’s function is limited by the maturity of its sensory organs and that it can’t influence motor activity in physiological condition before the end of the 2nd postnatal week, even if functional pathways from the labyrinth to the spinal cord seem to be already in place at birth.

Alcohol, recently named the most dangerous drug in the world, contributes to nearly 40% of violent crimes and fatal traffic accidents, increases risk of roughly 60 different diseases and injuries, and is responsible for 2.5 million deaths each year worldwide. Despite these staggering figures, treatments remain ineffective and riddled with adverse side effects, making successful use of even the most effective treatments unlikely. Moreover, many of the treatments, and the supporting research, have focused only on male subjects, despite sex differences in various alcohol-related behaviors. Human alcohol use is frequently accompanied by nicotine use, and vice versa, suggesting a common mechanism of the two drugs. In fact, alcohol may act through the same family of receptors as nicotine, the nicotinic acetylcholine receptors (nAChRs), eliciting similar activation of the reward pathway as nicotine and other drugs of abuse. Studies have shown that nAChRs containing the α4 and/or α6 subunits are involved in nicotine-induced activation of the reward pathway, leading to the hypothesis that these same receptor subtypes may be important for alcohol effects in the brain as well. Using male and female genetic mouse models and various behavioral assays, we have shown not only that these α4 and/or α6-containing nAChRs are involved in alcohol- related behaviors and activation of the reward pathway, but also show sex differences in this involvement. Uncovering the mechanism of alcohol in the brain, in males as well as in females, is an important step in developing targeted treatments for alcohol abuse.

In rheumatoid arthritis (RA), the expression of many pro-destructive/pro-inflammatory proteins depends on the transcription factor AP-1. Therefore, our aim was to analyze the presence and functional relevance of mutations in the coding regions of the AP-1 subunits of the fos and jun family in peripheral blood (PB) and synovial membranes (SM) of RA and osteoarthritis patients (OA, disease control), as well as normal controls (NC). Using the non-isotopic RNAse cleavage assay, one known polymorphism (T252C: silent; rs1046117; present in RA, OA, and NC) and three novel germline mutations of the cfos gene were detected: (i) C361G/A367G: Gln121Glu/Ile123Val, denoted as “fos121/123”; present only in one OA sample; (ii) G374A: Arg125Lys, “fos125”; and (iii) C217A/G374A: Leu73Met/Arg125Lys, “fos73/125”, the latter two exclusively present in RA. In addition, three novel somatic cjun mutations (604–606ΔCAG: ΔGln202, “jun202”; C706T: Pro236Ser, “jun236”; G750A: silent) were found exclusively in the RA SM. Tansgenic expression of fos125 and fos73/125 mutants in NIH-3T3 cells induced an activation of reporter constructs containing either the MMP-1 (matrix metalloproteinase) promoter (3- and 4-fold, respectively) or a pentameric AP-1 site (approximately 5-fold). Combined expression of these two cfos mutants with cjun wildtype or mutants (jun202, jun236) further enhanced reporter expression of the pentameric AP-1 construct. Finally, genotyping for the novel functionally relevant germline mutations in 298 RA, 288 OA, and 484 NC samples revealed no association with RA. Thus, functional cfos/cjun mutants may contribute to local joint inflammation/destruction in selected patients with RA by altering the transactivation capacity of AP-1 complexes.