Stress, personalidade, coping e bem-estar: relação com o sucesso e excelência em contextos de realização desportiva

Dissertação de mestrado integrado em Psicologia

Breeding activity of Scinax centralis (Anura, Hylidae) in Central Brazil

From January, 1997 to April, 1998, we studied breeding activity in a population of Scinax centralis Pombal & Bastos, 1996, in the state of Goiás, inside the Cerrado Biome, Brazil. The behavior of males and females in the choruses, the relationships between environmental variables and the presence of individuals, the spatial distribution pattern, amplexus and clutches were analyzed. The breeding season occurred from November to May. The majority of males began to call when they entered the chorus; they were defending their calling sites against other males. We found a positive correlation between the number of females and males in the choruses, but no significant correlation was observed between the operational sexual ratio (OSR, number of reproducing females/number of reproducing males) and the number of calling males. OSR was highly male-biased; on average, there were 40 males for each female. The presence of individuals was positively correlated with air temperature of two previous days and negatively correlated with rainfall on the observation day. Generally, males were non-randomly distributed and satellite males were observed. Females were larger and heavier than males. Egg number, but not diameter of the egg, was correlated with the female size.

Relations intergroupes : attribution à la discrimination et perception d'hostilité chez autrui

Résumé: La thèse que nous présentons s'intéresse aux phénomènes d'attribution d'intentions hostiles. Dodge (1980) observe que les individus agressifs ont tendance, en situation ambiguë, à sur-attribuer des intentions hostiles à leurs pairs, ce qui induit des réponses agressives. Pour l'auteur, l'attribution d'intentions hostiles est un médiateur entre certaines caractéristiques personnelles (l'agressivité) des individus, et le type de réponses qu'ils apportent aux situations. Cependant, les informations concernant l'appartenance groupale des "pairs" ne sont jamais prises en compte dans leurs études. Si ce processus est perméable à l'influence des normes et croyances (Bègue et Muller, 2006), aucune étude ne met en évidence quel serait l'impact d'informations groupales sur l'élaboration des réponses aux situations, dans le cadre de ce modèle. L'objectif de cette thèse est de montrer que l'attribution d'intentions hostiles peut être envisagée comme un processus agissant également à un niveau intergroupes et donc prenant en compte des informations groupales sur les individus. En s'inspirant du modèle de Dodge, nous avons émis l'hypothèse que les logiques intergroupes intervenaient dans l'interprétation des intentions des acteurs impliqués dans les interactions, afin de produire une réponse adaptée aux logiques intergroupes. Afin de tester cette hypothèse, nous avons suivi trois axes de recherches: Dans le premier de ces axes, nous avons introduit, dans le paradigme de Dodge, des informations .sur l'appartenance groupale des protagonistes de l'interaction (endogroupe vs exogroupe). Nous avons montré que le type de situation (ambiguë vs hostile) est moins important que l'information groupale dans la production d'une réponse à la situation (Étude 1). En outre, nous avons mis en évidence des processus différents selon la position des individus dans leur groupe (Étude 2). Dans le second axe, nous avons montré que si les différences de statut entre groupes n'influençaient pas directement le modèle de Dodge, elles interagissaient avec l'appartenance groupale et la clarté de la situation au niveau de l'attribution d'intentions hostiles (étude 3) et des intentions comportementales (Ettide 4). Dans le troisième et deriúer axe, nous avons introduit l'attribution d'intentions hostiles dans un processus de dévalorisation d'une cible expliquant un échec par la discrimination (Kaiser et Miller, 2001; 2003). Nous avons alors montré que l'attribution d'intentions hostiles médiatisait le lien entre l'attribution mobilisée pour expliquer l'événement et l'évaluation de la cible (Étude 5), et que ce type d'attribution était spécifique, aux intentions comportementales agressives (Études 6). Nous avons alors conclu sur la dimension sociale de l'attribution d'intentions hostiles et sur le fait qu'il s'agissait d'un élément permettant la construction d'une représentation des interactions sociales. Abstract The present thesis focuses on the phenomena of hostile intents attribution. Dodge (1980) observes that in ambiguous situations, aggressive people tend to over attribute hostile intents to others. This attribution leads them to respond aggressively. According to the author, hostile intents attribution mediates the link between some personal characteristics (aggressiveness for example) of individuals and their responses to the situation. However information related to participants group membership is always neglected in these studies. Begue and Muller (2006) showed that some beliefs could moderate the interaction between aggressiveness and hostile intents attribution on behaviors, but no study exhibited evidence of a similar effect with social information. The aim of this thesis is to show that hostile intents attribution needs to be considered at an intergroup level by taking into account people's group ineinbership. Based on the Dodge model, we formulated the hypothesis that intergroup strategies had an impact on actors' intents interpretations which in return should lead to different but adapted reactions to the situation. To test this hypothesis, three lines of research were developed. In the first line, we introduced, in the Dodge's paradigm, some information about the participants group membership (ingroup vs outgroup). We showed that when elaborating a response to a specific situation its nature (ambiguous vs hostile) had less impact than group membership information (Study 1). In addition, we highlighted some different processes according to the position of individuals in their group (Study 2). In the second line, we showed that if the differences between groups status didn't influence the Dodge model, they interacted with group membership and situation nature to influence hostile intents attribution (Study 3) and behaviors intents (Study 4). In the last line of research, we introduced hostile intents attribution within the process of derogation of a target explaining its failure by discrimination (Kaiser and Miller, 2001; 2003). We showed that hostile intents attribution mediated the link between the attibution mobilized to explain the failure and the derogation of the target (Study 5), and that this attribution type was specifically linked to aggressive behavior intents (Study 6). We finally concluded that hostile intents attribution imply an important social dimension which needs to be taken into account because involved in the construction of a representation of social interactions.

Quality Of Attachment, Perinatal Risk, And Mother-Infant Interaction In A High-Risk Premature Sample

Thirty-three families, each with a premature infant born less than 33 gestational weeks, were observed in a longitudinal exploratory study. Infants were recruited in a neonatal intensive care unit, and follow-up visits took place at 4 months and 12 months of corrected age. The severity of the perinatal problems was evaluated using the Perinatal Risk Inventory (PERI; A.P. Scheiner & M.E. Sexton, 1991). At 4 months, mother infant play interaction was observed and coded according to the CARE-index (P.M. Crittenden, 2003); at 12 months, the Strange Situation Procedure (SSP; M.D.S. Ainsworth, M.C. Blehar, E. Waters. & S. Wall, 1978) was administered. Results indicate a strong correlation between the severity of perinatal problems and the quality of attachment at 12 months. Based on the PERI, infants with high medical risks more frequently tended to be insecurely attached. There also was a significant correlation between insecure attachment and dyadic play interaction at 4 months (i.e., maternal controlling behavior and infant compulsive compliance). Moreover, specific dyadic interactive patterns could be identified as protective or as risk factors regarding the quality of attachment. Considering that attachment may have long-term influence on child development, these results underline the need for particular attention to risk factors regarding attachment among premature infants.

Expression of prox1, lymphatic endothelial nuclear transcription factor, in Kaposiform hemangioendothelioma and tufted angioma.

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare tumors mainly occurring in early childhood. Our recent results showed that ectopic overexpression of human Prox1 gene, a lymphatic endothelial nuclear transcription factor, promoted an aggressive behavior in 2 murine models of KHE. This dramatic Prox1-induced phenotype prompted us to investigate immunohistochemical staining pattern of Prox1, podoplanin (D2-40), LYVE-1, and Prox1/CD34 as well as double immunofluorescent staining pattern of LYVE-1/CD31 in KHE and TA, compared with other pediatric vascular tumors. For this purpose, we examined 75 vascular lesions: KHE (n=18), TA (n=13), infantile hemangioma (n=13), pyogenic granuloma (n=18), and granulation tissue (n=13). Overall, KHE and TA shared an identical endothelial immunophenotype: the neoplastic spindle cells were Prox1, podoplanin, LYVE-1, CD31, and CD34, whereas endothelial cells within glomeruloid foci were Prox1, podoplanin, LYVE-1, CD31, and CD34. The lesional cells of all infantile hemangiomas and pyogenic granulomas were negative for Prox1 in the presence of positive internal control. These findings provide immunophenotypic evidence to support a preexisting notion that KHE and TA are closely related, if not identical. Overall, our results show, for the first time, that Prox1 is an immunohistochemical biomarker helpful in confirming the diagnosis of KHE/TA and in distinguishing it from infantile hemangioma and pyogenic granuloma.

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia.

Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid leukemia and 34 patients with acute myeloid leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic myelomonocytic leukemia to acute myeloid leukemia by comparing the progressed chronic myelomonocytic leukemia cases with a cohort of chronic myelomonocytic leukemia cases that did not transform to acute myeloid leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Patients with acute myeloid leukemia ex chronic myelomonocytic leukemia were older (P<0.01) and less likely to receive aggressive treatment (P=0.02) than de novo acute myeloid leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid leukemia (17 months, P=0.002) but similar to post myelodysplastic syndrome acute myeloid leukemia. On multivariate analysis of all acute myeloid leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid leukemia following chronic myelomonocytic leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid leukemia cases.

Cancers cutanés envahissant la base du crâne [Skin cancers infiltrating the skull base].

Squamous cell and basocellular carcinoma of the face have an excellent prognosis. Nevertherless, a small proportion therefore of these cancers differs by a much more aggressive behavior, caracterised by a tendency to infiltrate the deep facial soft tissues and facial bones. The invasion of the craniofacial skeleton and the intracranial structures follows the embryonic fusion lines or the facial sensitive or motor nerves, sometimes years after the initial treatment. The development of craniofacial surgery, reconstruction techniques and conformational radiotherapy allows us now to offer curative guided treatments, for these advanced staged tumors with a remaining limited prognosis. A therapeutic benefit implies a rigorous selection of these patients.

Introduced ants in Galápagos (Floreana Island) : importance of competition, coexistence and agressive behaviors

Abstract Invasive species represent with fragmentation of habitat the most serious threats to biodiversity in the world. Galápagos Archipelago, as most oceanic islands, suffers a high rate of introduced animals and plants that affect equilibrium and biodiversity of this unique biota. Ants rank among the most devastating invaders. Their social organization confer them a high ability to adapt and to spread in new environments forming rapidly populous communities. We studied the ant community of Floreana Island composed mainly of introduced species (at least 1 S). Introduction events occurred successively during last century. The last record is Monomorium destructor arrived in the eighties. Our aim is to investigate the modalities of interaction and coexistence of these introduced species. We highlighted the competition hierarchy of the coexisting species using attractive food baits. Two species behave as competitively dominant by monopolizing an important part of resources. They are M. destructor restricted to a small area and the fire ant Solenopsis geminata widely distributed on the island. Then we evaluated the relative importance of abiotic factors and interspecific competition in structuring the community. Ecological data were collected and presence and abundance of species were estimated using different methods in a wide range of habitats. Several species showed preferences either for arid or for humid areas. The little fire ant Wasmannia auropunctata, awell-known devastating species when introduced, was exclusively found in moist habitat in and around the agricultural area situated in the upper and central part of thé island. It coexists with other species in several parts but in a restricted perimeter it excludes all other ants and worker's density on the ground is nearly 70 times higher than ant's density in similar habitats occupied by several species. But most opportunist tramp species establish everywhere without particular ecological requirement. Analyses of species co-occurrences at various levels didn't reveal any marked effect of competition in structuring ant's assemblages. We supposed that the lack ofcompetition-derived structure has to be attributed to the dynamic of the system. Indeed, across the successive census of 1996, 2003, 2004 and 2005, species distributions and abundances appeared to be highly variables. In particular harsh conditions occurring in dry season in certain parts seem to be limiting to S. geminatai. We suggest that huge variations in the local distribution of the dominant S. geminata disrupt the community organization. Finally we conducted artificial ant confrontations to evaluate to what extend an aggressive behavior at the worker level maybe linked to the ecological success of a species on the island. S. geminata was rather indifferent when confronted to a submissive species on food sources, suggesting that its competitive dominance is largely due to a numerical superiority. On the other hand M. destructor exhibits a strong agonistic behavior in similar confrontations. As soon as the presence of a competitor is detected, most workers were observed to abandon foraging and to take part in physical aggressions. Since it is still restricted nearby its introduction spot two decades after its arrival, we suggest that the energetic cost of such an aggressive behavior prevent it to spread on that island already highly colonized. Dominant invasive species such as the fire ants S. geminata and W. auropunctata have negative impacts on Galápagos fauna, disturbing the hatching of land tortoises and birds. But very little is known about the impact of other exotic ants. Indeed, impact on arthropods and generally on ground-dwelling organisms is very diffcult to evaluate. As a consequence of the dynamic character of Floreana I. ant community it is difficult to build models or to málce predictions on evolution of introduced ant fauna. But Camponotus macilentus, an abundant endemic species seems today to be little affected by introduced ant species thanks to its strong interference competition ability and its preference for arid and harsh environments. Résumé Les espèces envahissantes représentent, avec la fragmentation du paysage, la plus grande menace pour la biodiversité. L'archipel des Galápagos, comme la plupart des îles du Pacifique, compte un grand nombre d'espèces introduites qui menacent la biodiversité de ce milieu unique.. Les fourmis sont parmi les envahisseurs les plus dévastateurs. Leur organisation sociale leur permet de s'adapter et de se propager pour devenir rapidement abondantes. Nous avons étudié la communauté de fourmis sur l'île de Floreana principalement composée d'espèces introduites (au moins 15). Les introductions se sont succédées au cours du siècle précédent. La dernière espèce recensée est Monomorium destructor introduite dans les années 80. Notre objectif est de mettre à jour les modalités des interactions et de la coexistence de ces espèces introduites. Nous avons mis en évidence la hiérarchie de compétition des différentes espèces à l'aide d'appâts de nourriture. Deux espèces se comportent de façon dominante en monopolisant une part importante des ressources. Ce sont M. destructor, restreintes à un petit périmètre, et la fourmi de feu Solenopsis geminata, largement distribuée sur l'île. Nous avons évalué l'importance relative des facteurs abiotiques et de la compétition interspécifique dans la structuration des peuplements. Des données écologiques ont été collectées et la présence et l'abondance des espèces ont été estimées à l'aide de trois méthodes au sein d'une grande diversité d'habitats. Plusieurs espèces .montrent des préférences soit pour les milieux humides, soit pour les milieux arides. La petite fourmi de feu Wasmannia auropunctata, une espèce connue pour être dévastatrice dans ses sites d'introduction, est présente exclusivement dans les habitats humides dans et à proximité de la zone agricole située dans la partie centrale de l'île. Elle coexiste en plusieurs points avec d'autres espèces mais au sein d'un périmètre restreint elle exclut toute autre fourmi et atteint des densités record au sol presque 70 fois supérieures aux densités de fourmis observées sur les sites voisins occupés par plusieurs espèces. Mais la plupart des espèces vagabondes opportunistes s'établissent partout sans exigences écologiques particulières. Des analyses de cooccurrence d'espèces à plusieurs niveaux n'ont pas révélé de rôle marqué de la compétition dans la structuration des communautés. Nous supposons que l'absence d'une telle structure doit être attribuée à la dynamique du système. En effet, au cours des différents recensements de 1996-1997, 2003, 2004 et 2005, la distribution et l'abondance des espèces était très variable. En particulier, les conditions rudes qui règnent dans la zone aride durant la saison sèche semblent affecter particulièrement S. geminata. Nous suggérons que de fortes variations dans la distribution de l'espèce dominante perturbent l'orgaiùsation des communautés. Finalement nous avons effectué des confrontations artificielles pour évaluer dans quelle mesure un comportement agressif au niveau de l'ouvrière peut être lié au succès écologique d'une espèce sur l'île. S. geminata montre très peu de réaction face à une espèce subordonnée sur une même source de nourriture, ce qui laisse supposer que sa dominance est largement due à sa supériorité numérique. Par contre, dans des conditions similaires, M. destructor est fortement agressive. En présence d'un compétiteur, la plupart des ouvrières renoncent très vite à leur activité de fourragement pour agresser les individus de l'autre espèce. Puisque deux décennies après son introduction elle est toujours confinée à son point d'arrivée, nous supposons que le coût en énergie et en ouvrières de ce comportement très agressif est un obstacle à son expansion sur cette île déjà fortement colonisée. Les espèces envahissantes dominantes comme les fourmis de feu S. geminata et W. auropunctata sont connues pour leur impact négatif sur la faune des Galápagos, entre autre sur les jeunes des tortues terrestres et des oiseaux. Mais nous savons très peu de choses sur l'impact des autres espèces de fourmis introduites. En effet, l'impact sur les arthropodes, et plus généralement sur la faune du sol, est très difficile à évaluer. En raison du caractère dynamique de la communauté de fourmi de Floreana, il est difficile de construire des modèles et de faire des prédictions sur l'évolution des peuplements de fourmis introduites. Mais Camponotus macilentus, une espèce endémique abondante, semble aujourd'hui peu affectée par les espèces introduites grâce à ses capacités de compétition par interférence et sa préférence pour les milieux arides. Resumen Las, especies invasoras representan, junto con la fragmentación del paisaje, la mayor amenaza para la biodiversidad. El archipiélago de Galápagos, como la mayoría de las islas del Pacífico, cuenta con un gran número de especies introducidas que amenazan la biodiversidad de este lugar único. Las hormigas son uno de los invasores más devastadores. Su organización social les permite adaptarse y propagarse para ser rápidamente abundante. Estudiamos la comunidad de hormigas de la isla Floreana principalmente compuesta de especies introducidas (al menos 15). Las introducciones se sucedieron durante el siglo anterior. La última especie contabilizada es Monomorium destructor introducida en los años 80. Nuestro objetivo es poner al día las modalidades de las interacciones y de la coexistencia de estas especies introducidas. Pusimos de relieve la jerarquía de competencia de las distintas especies con ayuda de cebos de comida. Dos especies se implican de manera dominante monopolizando una parte importante de los recursos. Son M. destructor, limitado a un pequeño perímetro, y la hormiga de fuego Solenopsis geminata; ampliamente distribuida por la isla. Evaluamos la importancia relativa de los factores abióticos y de la competencia interespecífica en la estructuración de la communidad. Se recogieron algunos datos ecológicos y se consideraron la presencia y la abundancia de las especies con ayuda de tres métodos en una gran diversidad de hábitats. Varias especies muestran preferencias o por los medios húmedos, o por los medios áridos. La pequeña hormiga de fuego Wasmannia auropunctata, una especie conocida por ser devastadora en sus lugares de introducción, está presente exclusivamente en los hábitats húmedos y cerca de la zona agrícola situada en la parte central de la isla. Coexiste en varios puntos con otras especies pero en un perímetro limitado excluye a cualquier otra hormiga y alcanza densidades en el suelo casi 70 veces superiores a las densidades de hormigas observadas en los lugares vecinos ocupados por varias especies. Pero la mayoría de las especies vagabundas oportunistas se establecen por todas partes sin exigencias ecológicas particulares. Análisis de cooccurrencía de las especies a varios niveles no revelaron una grande importancía de la competencia en la estructuración de las comunidades. Suponemos que la ausencia de tal estructura Bebé ser por la dinámica del sistema. Efectivamente, durante los distintos censos de 1996-1997, 2003,.2004 y 2005, la distribución ? la abundancia de las especies eran muy variables. En particular, las condiciones drásticas que reinan en la zona árida durante la temporada seca parecen afectar especialmente a S. geminata. Sugerimos que fuertes variaciones en la distribución de la especie dominante perturben la organización de las comunidades. Finalmente efectuamos confrontaciones artificiales para evaluar hastá que punto un comportamiento agresivo a nivel de la obrera puede explicar el éxito ecológico de una especie en la isla. S. geminata muestra muy poca reacción ante una especie subordinada mientras comparten la misma comida, lo que deja suponer que su dominancia se debe a su superioridad numérica. Por el contrario, en condiciones similares, M. destructor es muy agresivo. En presencia de otra especie, la mayóría de las obreras renuncian muy rápidamente a alimentarse para atacar a los individuos de la otra especie. Puesto que dos décadas después de su introducción todavía se confina en su punto de llegada, suponemos que el coste en energía y en obreras de este comportamiento muy agresivo es un obstáculo a su extensión en esta isla ya muy colonizada. Las especiés invasoras dominantes como las hormigas de fuego S. geminata y W. auropunctata son conocidas por su impacto negativo en la fauna de Galápagos, entre otras cosas sobre los juveniles de las tortugas terrestres y pájaros. Pero sabemos muy poco sobre el impacto de las otras especies de hormigas introducidas. Efectivamente es muy difïcil de evaluar el impacto en los artrópodos, y más generalmente en la fauna del suelo. Debido al carácter dinámico de la comunidad de hormiga de Floreana, es diEcil construir modelos y hacer predicciones sobre la evolución de las poblaciones de hormigas introducidas. Pero Camponotus macilentus, una especie endémica abundante, parece poco afectadá hoy por las especies introducidas gracias a sus capacidades de competencia por interferencia y su preferencia por los medios áridos.

The impact of cyclin D1 mRNA isoforms, morphology and p53 in mantle cell lymphoma: p53 alterations and blastoid morphology are strong predictors of a high proliferation index.

BACKGROUND: Mantle cell lymphoma is a clinically heterogeneous disease characterized by overexpression of cyclin D1 protein. Blastoid morphology, high proliferation, and secondary genetic aberrations are markers of aggressive behavior. Expression profiling of mantle cell lymphoma revealed that predominance of the 3'UTR-deficient, short cyclin D1 mRNA isoform was associated with high cyclin D1 levels, a high "proliferation signature" and poor prognosis. DESIGN AND METHODS: Sixty-two cases of mantle cell lymphoma were analyzed for cyclin D1 mRNA isoforms and total cyclin D1 levels by real-time reverse transcriptase polymerase chain reaction, and TP53 alterations were assessed by immunohistochemistry and molecular analysis. Results were correlated with proliferation index and clinical outcome. RESULTS: Predominance of the short cyclin D1 mRNA was found in 14 (23%) samples, including four with complete loss of the standard transcript. TP53 alterations were found in 15 (24%) cases. Predominance of 3'UTR-deficient mRNA was significantly associated with high cyclin D1 mRNA levels (P=0.009) and more commonly found in blastoid mantle cell lymphoma (5/11, P=0.060) and cases with a proliferation index of >20% (P=0.026). Both blastoid morphology (11/11, P<0.001) and TP53 alterations (15/15, P<0.001) were significantly correlated with a high proliferation index. A proliferation index of 10% was determined to be a significant threshold for survival in multivariate analysis (P=0.01). CONCLUSIONS: TP53 alterations are strongly associated with a high proliferation index and aggressive behavior in mantle cell lymphoma. Predominance of the 3'UTR-deficient transcript correlates with higher cyclin D1 levels and may be a secondary contributing factor to high proliferation, but failed to reach prognostic significance in this study.

Molecular underpinning of extranodal NK/T-cell lymphoma.

Peripheral NK/T-cell lymphoma (PTCL) is a heterogeneous group of uncommon hematologic malignancies with aggressive clinical course and unfavorable prognosis. Extranodal NK/T-cell lymphoma, nasal type (NKTCL) is the most common extranodal entity worldwide, with heterogeneous geographic distribution, and it is characterized by its association with EBV, a nasal or less often extranasal presentation and aggressive behavior. Recent works using array-based technologies have provided novel insights into the pathogenesis and discovered new biomarkers with diagnostic and therapeutic implications in NKTCL. Gene expression profiling identified that most of the NKTCL are derived from activated natural killer cells with distinctively high expression of granzyme H compared to other PTCLs, which might serve as a new diagnostic biomarker. Frequent deletions and promoter methylations in PRDM1, ATG5, AIM1, FOXO3, HACE1 mapping to 6q21-q25, suggest their roles as potential tumor suppressors. The deregulation of oncogenic pathways (PDGF, JAK-STAT, AKT) provides a rationale for developing targeted therapies in the future.

Molecular pathways: emerging pathways mediating growth, invasion, and metastasis of tumors progressing in an irradiated microenvironment.

Radiotherapy is a well-established therapeutic modality in oncology. It provides survival benefits in several different cancer types. However, cancers relapsing after radiotherapy often develop into more aggressive conditions that are difficult to treat and are associated with poor prognosis. Cumulative experimental evidence indicates that the irradiated tumor bed contributes to such aggressive behavior. The involved mechanisms have for long remained elusive. Recent progress in the field revealed previously unrecognized cellular and molecular events promoting growth, invasion, and metastasis of tumors progressing in an irradiated microenvironment. Cellular mechanisms include inhibition of sprouting angiogenesis, formation of hypoxia, activation and differentiation of stromal cells, and recruitment of bone marrow-derived cells with vasculogenic and prometastatic activities. Identified pathways include TGF-β/ALK5, CXCL12/CXCR4, KITL/KIT, and CYR61/αVβ5 integrin. The availability of pharmacologic inhibitors impinging on these pathways opens novel opportunities for translational and clinical studies. These experimental results and ongoing work highlight the importance of the irradiated microenvironment in modulating the tumor response to radiotherapy and open new opportunities for the development of novel therapeutic strategies for patients with cancer who relapse after radiotherapy. Here, we review and discuss recent advances in the field and their translational and therapeutic implications to human cancer treatment.

Johtavatko väkivaltaiset kokemukset aggressiiviseen käytökseen?

English summary: Do violent experiences lead to aggressive behavior?

Pachycondyla obscuricornis as natural enemy of the spittlebug Deois flavopicta

The objective of this work was to evaluate the potential control of the ant Pachycondyla obscuricornis Emery (Hymenoptera Formicidae) on populations of nymphs of the spittlebug, Deois flavopicta Stal (Hemiptera Cercopidae). Foraging behavior and prey consumption rate of P. obscuricornis were evaluated. Field data revealed that P. obscuricornis does not show aggressive behavior against individuals of the same species, when they are not carrying a prey; they can patrol distances larger than 10 m searching for prey, and they can build their nest as close as 1 m from each other. The ant has a solitary patrolling habit, there is no recruitment behavior, and individuals dislocate fast, browsing on soil and vegetation for prey. Predation rate on spittlebug nymphs increased relative to the spittlebug abundance, reaching 93.8% of captured prey. Pachycondyla obscuricornis is a voracious predator and may control the population of spittlebugs in cultivated pastures.

Sensing pheromones : a role for the CNGA4 and TRPC2 proteins

Chez les mammifères, les phéromones sont des molécules clés dans la régulation des comportements sociaux au sein d'une espèce. Chez la souris, la détection de ces molécules se fait dans l'organe voméronasal (VNO] et implique le canal TRPC2 afin de dépolariser les neurones. Des différences de comportement entre des souris Trpc2-/- et des souris sans VNO suggèrent l'implication d'une autre protéine effectrice dans la voie de signalisation des phéromones. L'hypothèse étant que cette protéine formerait un canal hétéromérique avec TRPC2. CNGA4 est une protéine sans fonction connue dans le VNO des rongeurs. Elle appartient à la famille des protéines CNG qui joue un rôle important dans différentes voies de signalisation comme la vision ou l'olfaction. Etant donné sa présence dans le VNO, son rôle inconnu dans cet organe et son rôle important dans de nombreuses voies de signalisation, nous avons décidé d'étudier CNGA4 afin de connaître sa localisation, ses propriétés ou encore sa structure. Nous avons découvert que CNGA4 est exprimée dans les axons, les neurones immatures ainsi que sur les microvillosités des neurones de VNO. A l'aide de souris portant une version non fonctionnelle de CNGA4, nous avons pu montrer que cette protéine joue un rôle majeur dans la voie de signalisation des phéromones. Ainsi, les neurones du VNO portant une version non fonctionnelle de CNGA4 répondent moins fréquemment aux phéromones et par conséquent les phéromones activent également moins de neurones dans le bulbe olfactif accessoire, premier relais du VNO avec le cortex. Cette détection défaillante se traduit par une absence d'agressivité des souris mutantes ainsi que par une incapacité de ces souris à discriminer le sexe de leur conspécifique. Etant donné les propriétés similaires de CNGA4 et de TRPC2, nous avons supposé que les deux protéines pourraient interagir. Cette hypothèse a été confortée par l'observation que CNGA4 n'est plus exprimée dans les microvillosités du VNO des souris Trpc2-/-. A l'aide d'expériences d'expression hétérologue, nous avons pu observer que les deux protéines interagissent et forment un canal activé par un analogue du diacylglycérol suggérant que ce canal est fonctionnel. Ces résultats indiquent que CNGA4 formerait un canal hétéromérique avec TRPC2 et aurait dans ce canal une fonction modulatrice. Des expériences complémentaires sont nécessaires afin de connaître le rôle de chacune de ces protéines dans la voie de signalisation des phéromones. Sensing pheromones: a role for the CNGA4 and TRPC2 proteins Mammalian pheromones are key chemical signals in the regulation of intraspecies social behaviors. Detection of these pheromones, which takes place in sensory neurons of the vomeronasal organ (VNO), implies the activation of the transient receptor potential canonical channel 2 (TRPC2) as the final effector. Interestingly, discrepancies between Trpc2 /- mice and mice lacking a VNO suggest the implication of another protein in the pheromone signaling pathway. This protein could either form a heteromeric channel with TRPC2 or a separate homomeric ion channel. The cyclic nucleotide-gated channel subunit CNGA4 is also expressed in the rodent VNO but its role and properties in this organ remain unknown. CNGA4 belongs to the CNG channel family which is playing an important role in different sensory pathways such as in light and odorant detection. We thus decided to study the role of the CNGA4 protein in the mouse VNO. We found CNGA4 to be expressed in axons, dendrites and in the sensory microvilli. Using mice bearing a non-functional form of CNGA4 we further demonstrated the importance of the CNGA4 protein for the pheromone signaling pathway as neurons from mutant mice were responding less frequently to chemosensory cues. As a result, mutant mice displayed a non-aggressive behavior and an impaired sexual discrimination ability. Based on the CNGA4 localization and its role in the pheromone signaling pathway we hypothesized a possible interaction between CNGA4 and TRPC2 forming a heteromeric channel. First evidences for this interaction came from the absence of CNGA4 expression in the sensory microvilli of Trpc2-/- mice. Second, using transfected HEK cells as an expression system we could observe that CNGA4 and TRPC2 interact and translocate to the plasma membrane. Perfusion of a DAG analogue on co-transfected HEK cells resulted in a strong calcium entry suggesting that the two proteins form a functional channel. These results might suggest a modulatory role for CNGA4 in a heteromeric TRPC2+CNGA4 ion channel. Further experiments will give more insights on the combined role of these transduction ion channels in pheromone detection.

Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.

Mephedrone is a drug of abuse marketed as 'bath salts'. There are discrepancies concerning its long-term effects. We have investigated the neurotoxicity of mephedrone in mice following different exposition schedules. Schedule 1: four doses of 50 mg/kg. Schedule 2: four doses of 25 mg/kg. Schedule 3: three daily doses of 25 mg/kg, for two consecutive days. All schedules induced, in some animals, an aggressive behavior and hyperthermia as well as a decrease in weight gain. Mephedrone (schedule 1) induced dopaminergic and serotoninergic neurotoxicity that persisted 7 days after exposition. At a lower dose (schedule 2) only a transient dopaminergic injury was found. In the weekend consumption pattern (schedule 3), mephedrone induced dopamine and serotonin transporter loss that was accompanied by a decrease in tyrosine hydroxylase and tryptophan hydroxylase 2 expression one week after exposition. Also, mephedrone induced a depressive-like behavior, as well as a reduction in striatal D2 density, suggesting higher susceptibility to addictive drugs. In cultured cortical neurons, mephedrone induced a concentration-dependent cytotoxic effect. Using repeated doses for 2 days in an elevated ambient temperature we evidenced a loss of frontal cortex dopaminergic and hippocampal serotoninergic neuronal markers that suggest injuries at nerve endings.