The impact of triathlon training and racing on athletes' general health.

Although the sport of triathlon provides an opportunity to research the effect of multi-disciplinary exercise on health across the lifespan, much remains to be done. The literature has failed to consistently or adequately report subject age group, sex, ability level, and/or event-distance specialization. The demands of training and racing are relatively unquantified. Multiple definitions and reporting methods for injury and illness have been implemented. In general, risk factors for maladaptation have not been well-described. The data thus far collected indicate that the sport of triathlon is relatively safe for the well-prepared, well-supplied athlete. Most injuries 'causing cessation or reduction of training or seeking of medical aid' are not serious. However, as the extent to which they recur may be high and is undocumented, injury outcome is unclear. The sudden death rate for competition is 1.5 (0.9-2.5) [mostly swim-related] occurrences for every 100,000 participations. The sudden death rate is unknown for training, although stroke risk may be increased, in the long-term, in genetically susceptible athletes. During heavy training and up to 5 days post-competition, host protection against pathogens may also be compromised. The incidence of illness seems low, but its outcome is unclear. More prospective investigation of the immunological, oxidative stress-related and cardiovascular effects of triathlon training and competition is warranted. Training diaries may prove to be a promising method of monitoring negative adaptation and its potential risk factors. More longitudinal, medical-tent-based studies of the aetiology and treatment demands of race-related injury and illness are needed.

Mitochondria: Sovereign of inflammation?

NLRP3 inflammasome-dependent inflammatory responses are triggered by a variety of signals of host danger, including infection, tissue damage and metabolic dysregulation. How these diverse activators cause inflammasome activation is poorly understood. Recent data suggest that the mitochondria integrate these distinct signals and relay this information to the NLRP3 inflammasome. Dysfunctional mitochondria generate ROS, which is required for inflammasome activation. On the contrary, the NLRP3 inflammasome is negatively regulated by autophagy, which is a catabolic process that removes damaged or otherwise dysfunctional organelles, including mitochondria. In addition to the processing and secretion of pro-inflammatory cytokines such as IL-1β, NLRP3 inflammasome activation also influences cellular metabolic pathways such as glycolysis and lipogenesis. Mapping the connections between mitochondria, metabolism and inflammation is of great interest, as malfunctioning of this network is associated with many chronic inflammatory diseases.

Orexin/hypocretin (Orx/Hcrt) transmission and drug-seeking behavior: is the paraventricular nucleus of the thalamus (PVT) part of the drug seeking circuitry?

The orexin/hypocretin (Orx/Hcrt) system has long been considered to regulate a wide range of physiological processes, including feeding, energy metabolism, and arousal. More recently, concordant observations have demonstrated an important role for these peptides in the reinforcing properties of most drugs of abuse. Orx/Hcrt neurons arise in the lateral hypothalamus (LH) and project to all brain structures implicated in the regulation of arousal, stress, and reward. Although Orx/Hcrt neurons have been shown to massively project to the paraventricular nucleus of the thalamus (PVT), only recent evidence suggested that the PVT may be a key relay of Orx/Hcrt-coded reward-related communication between the LH and both the ventral and dorsal striatum. While this thalamic region was not thought to be part of the "drug addiction circuitry," an increasing amount of evidence demonstrated that the PVT-particularly PVT Orx/Hcrt transmission-was implicated in the modulation of reward function in general and several aspects of drug-directed behaviors in particular. The present review discusses recent findings that suggest that maladaptive recruitment of PVT Orx/Hcrt signaling by drugs of abuse may promote persistent compulsive drug-seeking behavior following a period of protracted abstinence and as such may represent a relevant target for understanding the long-term vulnerability to drug relapse after withdrawal.

Physiological function of PARbZip circadian clock-controlled transcription factors.

PARbZip proteins (proline and acidic amino acid-rich basic leucine zipper) represent a subfamily of circadian transcription factors belonging to the bZip family. They are transcriptionally controlled by the circadian molecular oscillator and are suspected to accomplish output functions of the clock. In turn, PARbZip proteins control expression of genes coding for enzymes involved in metabolism, but also expression of transcription factors which control the expression of these enzymes. For example, these transcription factors control vitamin B6 metabolism, which influences neurotransmitter homeostasis in the brain, and loss of PARbZip function leads to spontaneous and sound-induced epilepsy that are frequently lethal. In liver, kidney, and small intestine, PAR bZip transcription factors regulate phase I, II, and III detoxifying enzymes in addition to the constitutive androstane receptor (CAR), one of the principal sensors of xenobiotics. Indeed, knockout mice for the three PARbZip transcription factors are deficient in xenobiotic detoxification and display high morbidity, high mortality, and accelerated aging. Finally, less than 20% of these animals reach an age of 1 year. Accumulated evidences suggest that PARbZip transcription factors play a role of relay, coupling circadian metabolism of xenobiotic and probably endobiotic substances to the core clock circuitry of local circadian oscillators.

L'exception sportive : champions noirs et culture coloniale (1900-1939)

4e de couv.: Comment la France a-t-elle été colonisée par son Empire ? En traitant du fait national tel qu'il a été modelé par l'idéologie coloniale, ce livre renverse les perspectives. Pour légitimer leurs lointaines conquêtes, la monarchie, l'empire et la république ont conçu, organisé, relayé auprès des Français une culture coloniale. Le cinéma et le théâtre, le sport et l'école, la littérature et la presse, les arts, la publicité, la chanson, sans oublier l'armée, les comités coloniaux, les expositions se sont chargés de diffuser quêtes scientifiques, fascinations exotiques, fiertés patriotiques ainsi qu'intérêts économiques et politiques. A l'heure où la France éprouve la difficulté de rassembler dans un destin commun des mémoires divisées, ce sont les grandes lignes de ce "passé qui ne passe pas" et les méandres d'une utopie coloniale que ce recueil retrace, de la première abolition de l'esclavage aux présents débats sur la "repentance". Une somme.

Contrasting the functional properties of GABAergic axon terminals with single and multiple synapses in the thalamus

Diverse sources of GABAergic inhibition are a major feature of cortical networks, but distinct inhibitory input systems have not been systematically characterized in the thalamus. Here, we contrasted the properties of two independent GABAergic pathways in the posterior thalamic nucleus of rat, one input from the reticular thalamic nucleus (nRT), and one "extrareticular" input from the anterior pretectal nucleus (APT). The vast majority of nRT-thalamic terminals formed single synapses per postsynaptic target and innervated thin distal dendrites of relay cells. In contrast, single APT-thalamic terminals formed synaptic contacts exclusively via multiple, closely spaced synapses on thick relay cell dendrites. Quantal analysis demonstrated that the two inputs displayed comparable quantal amplitudes, release probabilities, and multiple release sites. The morphological and physiological data together indicated multiple, single-site contacts for nRT and multisite contacts for APT axons. The contrasting synaptic arrangements of the two pathways were paralleled by different short-term plasticities. The multisite APT-thalamic pathway showed larger charge transfer during 50-100 Hz stimulation compared with the nRT pathway and a greater persistent inhibition accruing during stimulation trains. Our results demonstrate that the two inhibitory systems are morpho-functionally distinct and suggest and that multisite GABAergic terminals are tailored for maintained synaptic inhibition even at high presynaptic firing rates. These data explain the efficacy of extrareticular inhibition in timing relay cell activity in sensory and motor thalamic nuclei. Finally, based on the classic nomenclature and the difference between reticular and extrareticular terminals, we define a novel, multisite GABAergic terminal type (F3) in the thalamus.

Témoigner de son pâtir et de l'agir de Dieu. Les épreuves d'une communauté charismatique

On tentera de montrer, à partir de l'analyse d'un culte dominical survenu dans une communauté (évangélique) charismatique de Genève, comment les témoignages d'individus atteints par la souffrance viennent reconfigurer la compréhension que la communauté ecclésiale se fait d'elle-même et de ses rapports à la divinité. Pour la plupart, ces personnes sont atteintes de maux auxquels les prières de guérison, les impositions des mains ou les onctions d'huile n'ont pu remédier. Parallèlement aux souffrances de ces individus, la communauté traverse une série d'épreuves. De sorte que la présence des uns pousse les autres à s'interroger : « Pourquoi Dieu n'intervient-il pas ? Les aurait-il abandonnés ? Pour quelles raisons nos prières sont-elles inefficaces ? Et s'ils les a abandonnés, nous aurait-il également délaissés ? ». L'analyse des prises de paroles et de la configuration liturgique de la célébration constitue le corps de l'article. Au terme du culte, le déplacement des auditeurs dans l'espace de la salle dit, au propre et au figuré, le rassemblement de le communauté autour de ceux des siens qui souffrent, ainsi que la reconnaissance que cette souffrance participe de celle qui affecte la communauté dans son ensemble. Il y a lieu d'y voir la réponse à un appel formulé par le pasteur et relayé par les témoins. Les témoignages et la prière disent premièrement le lien qui unit une communauté de croyants avec le divin, soit la manière dont elle se reconnaît habitée par la divinité. Il y a une continuité entre les corps - sains, malades ou guéris - des fidèles et les façons qu'a le corps ecclésial de s'envisager et de concevoir ses limites.

Vascular continuity, cell axialization and auxin.

Phytohormones have been implicated in vascular development in various ways, but their precise function and the extent of their influence is still controversial. Recent results from experimental manipulation of developing organs and Arabidopsis developmental genetics support a role for polar auxin flow in cell axis formation within the vascular system and, interestingly, also in the embryonic establishment of the plant body axis. Vascular responses to auxin transport inhibition indicate patterns of auxin distribution during leaf development and new technologies may enable these predictions to be tested within the near future. Moreover, recently discovered Arabidopsis axialisation mutants seem to identify essential genes that relay auxin signals in vascular development. A first gene in this class, MONOPTEROS (MP) has been cloned and encodes a transcription factor capable of binding to auxin response elements in the control regions of auxin regulated genes. Molecular identification of further axialisation genes may provide access to a mechanistic understanding of plant cell axis formation.

DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB.

Detection of viral nucleic acids is central to antiviral immunity. Recently, DAI/ZBP1 (DNA-dependent activator of IRFs/Z-DNA binding protein 1) was identified as a cytoplasmic DNA sensor and shown to activate the interferon regulatory factor (IRF) and nuclear factor-kappa B (NF-kappaB) transcription factors, leading to type-I interferon production. DAI-induced IRF activation depends on TANK-binding kinase 1 (TBK1), whereas signalling pathways and molecular components involved in NF-kappaB activation remain elusive. Here, we report the identification of two receptor-interacting protein (RIP) homotypic interaction motifs (RHIMs) in the DAI protein sequence, and show that these domains relay DAI-induced NF-kappaB signals through the recruitment of the RHIM-containing kinases RIP1 and RIP3. We show that knockdown of not only RIP1, but also RIP3 affects DAI-induced NF-kappaB activation. Importantly, RIP recruitment to DAI is inhibited by the RHIM-containing murine cytomegalovirus (MCMV) protein M45. These findings delineate the DAI signalling pathway to NF-kappaB and suggest a possible new immune modulation strategy of the MCMV.

La ligne libre : un paradigme à la croisée de la philosophie et de la littérature de voyage dans la première moitié du XXème siècle : le corps et le paysage chez Victor Segalen, Blaise Cendrars et Henri Michaux

Fondée sur un corpus d'écrivains-voyageurs qui sont symptomatiques des changements importants affectant la question de l'espace dans la première moitié du XXème siècle, cette étude tire profit de la grande polyvalence de la problématique du paysage pour proposer un véritable dialogue interdisciplinaire entre littérature et philosophie. Cette perspective est largement favorisée par les écrivains eux-mêmes qui ont indiscutablement lié leur entreprise poétique à des enjeux épistémiques recoupant les préoccupations des scientifiques, médecins, géographes ou philosophes de leur temps. Un certain nombre d'interrogations nous sont apparues caractéristiques de cette période de l'histoire des voyages. Victor Segalen, Blaise Cendrars et Henri Michaux ont été particulièrement sensibles à cette angoisse d'époque liée à l'amenuisement du monde, c'est-à- dire au raccourcissement des distances entre continents suite aux développements des moyens de transport et la perte des « espaces blancs » de la carte, conséquence directe des entreprises exploratrices du XIXème siècle. A la déréliction qui s'empare du voyageur moderne face à la disparition des zones inconnues s'est ajouté l'effroi provoqué par la seconde loi thermodynamique du biologiste allemand Ernst Haeckel, qui, avec sa théorie de l'entropie, a fait craindre à plusieurs générations que la matière de l'univers tendrait vers une simplification toujours plus grande, et que le globe terrestre, à l'image du cosmos, ressemblerait peu ou prou à un immense magma de glace. Il est remarquable de constater à quel point ces trois auteurs ont développé une sorte d'outillage conceptuel commun propre à diagnostiquer cette crise et à la résoudre en élaborant une nouvelle manière de se rapporter à l'espace et de décrire le paysage. Ce nouveau paradigme qui modélise un autre type de relation à l'extérieur est solidaire de courants de pensée post-rationalistes qui de Nietzsche à Gilles Deleuze, en passant par Bergson et la phénoménologie, ont conduit à un démantèlement de la conception cartésienne de la conscience dans son rapport à l'étendue. Aux croisements de la philosophie et de la littérature se construit durant la première moitié du XXème siècle un nouveau modèle de représentation du paysage qui passe par l'élaboration de la ligne libre. Celle-ci décrit une manière de dire le réel qui ne consiste pas à en reproduire les composantes de façon fidèle, mais à tracer le mouvement énergétique par lequel le corps se rapporte à l'espace de manière dynamique et variée. Proche du terme de diagramme, exploité par Deleuze et relayé par le géographe Jean-Marc Besse, il consiste en un schème du réel qui s'élabore en cours d'expérience et ouvre sur une réalité à venir. De ce point de vue, la ligne libre définit une manière de se rapporter au réel qui remet en question les théories paysagères fondées sur Vartialisation. En prenant appui sur cette proximité d'intérêt entre une certaine philosophie et la littérature de voyage de la première moitié du XXème siècle, cette étude montre que la construction de ce nouveau paradigme permet de mettre en évidence un type de transfert peu conventionnel entre ces deux champs des sciences humaines. Car Segalen, Cendrars et Michaux n'ont pas vraiment repris aux philosophes des concepts, des syllogismes ou même des pensées, mais se sont approprié une figure dont ils ont libéré l'imaginaire sémantique. En lecteurs émerveillés de Nietzsche, ils ont surtout vu dans le voyageur Zarathoustra et dans sa manière de se déplacer dans le paysage, une façon stratégique de répondre à la crise de l'entropie. Mais si Zarathoustra incarne le mouvement de la ligne libre en lui conférant une valeur épistémique, il constitue également une figure imprégnée par la littérature de voyage et le genre de l'aventure. De ce point de vue, il apparaît que le développement de ce paradigme est redevable aussi bien de la philosophie que de la littérature de voyage et qu'une brève histoire de son élaboration révèle qu'une sémantique viatique accompagne la conception philosophique de cette ligne libre auprès des philosophes qui s'en approprient le modèle (Nietzsche, Bergson, Husserl, Heidegger, Merleau-Ponty, Deleuze).

Evidence for segregated and integrative connectivity patterns in the human Basal Ganglia.

Detailed knowledge of the anatomy and connectivity pattern of cortico-basal ganglia circuits is essential to an understanding of abnormal cortical function and pathophysiology associated with a wide range of neurological and neuropsychiatric diseases. We aim to study the spatial extent and topography of human basal ganglia connectivity in vivo. Additionally, we explore at an anatomical level the hypothesis of coexistent segregated and integrative cortico-basal ganglia loops. We use probabilistic tractography on magnetic resonance diffusion weighted imaging data to segment basal ganglia and thalamus in 30 healthy subjects based on their cortical and subcortical projections. We introduce a novel method to define voxel-based connectivity profiles that allow representation of projections from a source to more than one target region. Using this method, we localize specific relay nuclei within predefined functional circuits. We find strong correlation between tractography-based basal ganglia parcellation and anatomical data from previously reported invasive tracing studies in nonhuman primates. Additionally, we show in vivo the anatomical basis of segregated loops and the extent of their overlap in prefrontal, premotor, and motor networks. Our findings in healthy humans support the notion that probabilistic diffusion tractography can be used to parcellate subcortical gray matter structures on the basis of their connectivity patterns. The coexistence of clearly segregated and also overlapping connections from cortical sites to basal ganglia subregions is a neuroanatomical correlate of both parallel and integrative networks within them. We believe that this method can be used to examine pathophysiological concepts in a number of basal ganglia-related disorders.

Synapse formation in adult barrel cortex following naturalistic environmental enrichment.

Environmental enrichment paradigms in adult laboratory animals, consisting of physical, perceptual, and social stimulation, have been shown to affect synapse and cell morphology in sensory cortex and enhance learning ability, whereas enrichment, which is in harmony with the animal's natural habitat may have even greater implications for plasticity. Previous studies in our laboratory have shown that whisker stimulation induced the formation of synapses and spines in the corresponding barrel. In the present study adult C57/Bl6J female laboratory mice at 6 weeks of age were placed during 2 months in a protected enrichment enclosure in a forest clearing at the Chisti Les Biological Station, Tvier, Russia. We analyzed neuropil ultrastructure in the C2 barrel using serial-section electron microscopy on a total of eight mice (n=4 enriched, n=4 standard cagemate controls). Quantitative analyses of volumes of neuropil showed a significant increase in excitatory and inhibitory synapses on spines and excitatory synapses on dendritic shafts in the C2 barrel in the enriched group compared with standard cagemate controls. These results demonstrate that naturalistic experience alters the synaptic circuitry in layer IV of the somatosensory cortex, the first cortical relay of sensory information, leaving a lasting trace that may guide subsequent behavior.

Postnatal expression pattern of calcium-binding proteins in organotypic thalamic cultures and in the dorsal thalamus in vivo.

The present study describes the postnatal expression of calbindin, calretinin and parvalbumin and glutamic acid decarboxylase (GAD) and microtubule-associated protein 2 (MAP2) in organotypic monocultures of rat dorsal thalamus compared to the thalamus in vivo. Cultures were maintained for up to 7 weeks. Cortex-conditioned medium improved the survival of thalamic cultures. MAP2-immunoreactive material was present in somata and dendrites of small and large-sized neurons throughout the cultures. Parvalbumin immunoreactivity was present in larger multipolar or bitufted neurons along the edge of a culture. These neurons also displayed strong parvalbumin mRNA and GAD mRNA expression, and GABA immunoreactivity. They likely corresponded to cells of the nucleus reticularis thalami. Parvalbumin mRNA, but neither parvalbumin protein nor GAD mRNA, was expressed in neurons with large somata within the explant. They likely represented relay cells. GAD mRNA, but not parvalbumin mRNA, was expressed in small neurons within the explants. Small neurons also displayed calbindin- and calretinin-immunoreactivity. The small neurons likely represented local circuit neurons. The time course of expression of the calcium-binding proteins revealed that all were present at birth with the predicted molecular weights. A low, but constant parvalbumin expression was observed in vitro without the developmental increase seen in vivo, which most likely represented parvalbumin from afferent sources. In contrast, the explantation transiently downregulated the calretinin and calbindin expression, but the neurons recovered the expression after 14 and 21 days, respectively. In conclusion, thalamic monocultures older than three weeks represent a stable neuronal network containing well differentiated neurons of the nucleus reticularis thalami, relay cells and local circuit neurons.

Symptoms of chronic stress at work in NGO workers

Working in a NGO often involves providing life saving resources (food, medicine, equipment, water, etc) to needy populations around the globe. Such duty requires highly dedicated employees and humanitarian workers are said to face a hign degree of pressure in their daily work. Despite the evidence of taxing work demands, and a high potential for stress related problems, very few studies on occupational chronic stress have specifically looked at NGO workers. Assuming that "field stress" can relay to workers at headquarters, we carried out an exploratory study about occupational health among employees of a NGO's headquarters. We sent a questionnaire to all employees (N=130) of a NGO headquarters located in Switzerland. We used the TST questionnaire (French version of the Langner's questionnaire on psychiatric symptoms) to identify cases with potential mental health problems. We also included in the questionnaire some items about motivation, acknowledgment, work-life balance, job demand, and autonomy. A total of 75 employees answered our questionnaire (57% response rate). 44% of our sample were men (n=33) and 56% were women (n=42). The mean age was of 40 years (SD=7.6). 56% were working at the headquarters of the NGO in questions as of 2 years or less. Not surprisingly, a majority of respondents reported to be highly motivated (74%) and the meaning of work was important for 80% of them. However, 35% indicated having problems in conciliating their private and professional life. Most frequent reported symptoms included feeling "weak all over" (81%), having "trouble getting asleep often" (35%), "clogging in nose" (35%), feeling "nervous often" (33%), and "memory not all right" (33%). The score for psychiatric symptoms was high in 8 (11%) employees whose health might therefore be at risk. In comparison, other sudies showed that this proportion was 9% for French teachers and 16% for sales personnel1. Results show that symptoms of mental health problems do occur among NGO workers. Some of these symptoms are known to be linked to occupational stress. Chronic stress manifests itself first in non-specific symptoms (e.g. fatigue) and later in specific pathologies. This could explain the relatively low proportion of cases with a high score in Langner's scale than was expected. Therefore, we hypothesize a healthy worker effect. The fact that our sample is 40 years old in average, and that the turnover is quite high can also support this hypothesis. Further research is needed in order to better understand occupational stress in this specific population. An upcoming study will investigate the role of organizational factors associated with health complaints. Therefore, a longitudinal survey including quantitative and qualitative methods is appropriate.

Study of the physiological role of RasGAP cleavage

Résume Les caspases sont un groupe de protéases à cystéine qui s?activent lors de l'apoptose. Leur activation induit le clivage de nombreuses cibles intracellulaires, conduisant à l'activation de voies pro-apoptotiques et finalement au démantèlement des cellules. Cependant, des caspases ont été décrites dans de nombreux autres processus indépendants de l'apoptose, notamment dans la physiologie des cellules hématopoïétiques, des cellules musculaires, des cellules de la peau et des neurones. Comment est-ce que les cellules réconcilient-elles ces deux fonctions distinctes? Une partie de la réponse réside dans la nature des substrats qu'elles clivent. Certains substrats, une fois clivées, deviennent anti-apoptotiques. RasGAP est une cible des caspases et contient deux sites spécifiques de clivage par les caspases. Lorsque le niveau d?activité des caspases est faible le clivage de RasGAP produit un fragment N-terminal qui active un signal antiapoptotique, relayé par la voie de Ras/PI3K/Akt. Lorsque le niveau d?activité des caspases est plus élevé le fragment RasGAP N-terminal est à nouveau clivé, perdant de ce fait ses propriétés anti-apoptotiques. Dans cette étude, nous avons mis en évidence que l'activation de la voie Ras/PI3K/Akt induite par le fragment RasGAP N-terminal dépend de RasGAP lui-même. Par ailleurs, dans le but d?étudier l?importance du clivage de RasGAP dans un contexte physiologique, nous avons développé un modèle animal exprimant une gêne mutée de RasGAP de sorte que la protéine est devenu insensible a l?action de caspases. Les données préliminaires obtenues montrent que le clivage de RasGAP n'est pas indispensable pour le développement et l?homéostasie chez la souris. Finalement, nous avons développé une souris transgénique surexprimant le fragment de RasGAP N-terminal dans les cellules ß du pancréas. Les animaux obtenus ne montrent pas de symptômes dans les conditions basales bien qu?ils soient plus résistants au diabète induit expérimentalement. Ces résultats montrent que la surexpression du fragment N-terminal de RasGAP protége efficacement les cellules ß du pancréas de l?apoptose induite par le stress sans pourtant affecter d?autres paramètres physiologiques des Ilot de Langerhans.<br/><br/>Caspases are a series of proteases that are activated during apoptosis. Their activation causes the cleavage of numerous intracellular targets, which leads to cell dismantling and activation of pro-apoptotic pathways. Caspases have been found to be involved in the physiology of numerous cell types including haematopoietic cells, muscle cells, skin cells and neurons. How cells conciliate these two opposite functions? Part of the answer lies in the nature of the substrates they cleave. Some substrates become anti-apoptotic once cleaved by caspases. RasGAP is a caspase substrate that possesses two conserved caspase-cleavage sites. At low caspase activity, RasGAP is first cleaved and the generated N-terminal fragment activates a potent anti-apoptotic signal, mediated by the Ras/PI3K/Akt pathway. At higher caspase activity, the N-terminal fragment is further cleaved thereby losing its anti-apoptotic properties. In the present study we show that the activation of the Ras/PI3K/Akt pathway mediated by RasGAP N-terminal fragment is dependent on RasGAP itself. Moreover, to study the role of RasGAP cleavage in a physiological model, we have developed a knock-in mouse model expressing a RasGAP mutant that is not cleavable by caspases. Preliminary data shows that RasGAP cleavage is not required for normal development and homeostasis in mice. Finally, we have developed a transgenic mouse model overexpressing RasGAP N-terminal fragment in the ß-cell of the pancreas. In basal conditions, these mice show no difference with their wt counterparts. However, they are protected against experimentally induced diabetes. These results indicate that fragment N can protect ? cells from stress-induced apoptosis without affecting other physiological parameters of the Islets.