Le risque comme culture de la temporalité

Le concept de risque tente de rendre compte de discours et de pratiques qui s’appuient sur une connaissance plus ou moins formalisée de ce qui pourrait advenir. Si son origine remonte au Moyen Âge, c’est au cours de la période moderne que certains groupes sociaux ont commencé à interpréter des expériences et à justifier des décisions en se réclamant d’un nouveau discours sur l’avenir, le risque. Ce discours est alors étroitement lié aux pratiques émergentes de l’assurance, de même qu’à l’invention, dans le dernier tiers du xviie siècle, du calcul des probabilités. Au cours des siècles qui ont suivi, l’affranchissement graduel de la société moderne à l’égard de la tradition a été accompagné d’un approfondissement continuel des discours et des usages du risque, non seulement au sein des pratiques de prévoyance et de la science probabilitaire, mais également dans le gouvernement même des sociétés. D’ailleurs, ces dernières furent progressivement conçuescomme des corps gouvernables, à travers l’épistémologie des sciences naturelles et de la médecine qui donnaient naissance à un savoir sur la nature et sur l’homme, selon une approche à la fois épidémiologique et clinique des risques. Si bien que, de nos jours, tout tend désormais à être décliné en termes de risques, du réchauffement climatique à la crise économique, de la pauvreté à la criminalité, des pandémies au terrorisme, du rôle de l’État à celui des experts. Selon certains théoriciens du risque, ces usages et ces discours auraient pris de plus en plus d’importance au point de devenir le nœud des enjeux qui structurent désormais l’ensemble des dimensions de l’existence collective. Voilà, en peu de mots, sur quel grand processus historique complexe ce livre se penche

Longitudinal study of childhood sleep trajectories and adolescent mental health problems

Abstract Study objective To investigate whether childhood sleep trajectories are associated with mental health symptoms such as social phobia, generalized anxiety, depression, attention deficit hyperactivity disorder (ADHD), conduct problems, and opposition at age 15. Methods A total of 2120 children took part in the Quebec Longitudinal Study of Child Development. Childhood sleep trajectories were computed from maternal reports at 2.5, 3.5, 4, 6, 8, 10, and/or 12 years. At age 15, 1446 adolescents filled out mental health and sleep questions. A path analysis model was assessed in the full sample. Results Four childhood nocturnal sleep duration trajectories were identified: (1) a short pattern (7.5%), (2) a short-increasing pattern (5.8%), (3) a 10 hours pattern (50.7%), and (4) an 11 hours pattern (36.0%). Three childhood sleep latency trajectories were found: (1) a short pattern (31.7%), (2) an intermediate pattern (59.9%), and (3) a long pattern (8.4%). Finally, two childhood wakefulness after sleep-onset trajectories were found: (1) a normative pattern (73.0%) and (2) a long pattern (27.0%). The path analysis model indicated that children following a long childhood sleep latency trajectory were more likely to experience symptoms of depression (β = 0.06, 95% CI: 0.01 to 0.12), ADHD (β = 0.07, 95% CI: 0.02 to 0.13), conduct problems (β = 0.05, 95% CI: 0.00 to 0.10) and opposition (β = 0.08, 95% CI: 0.02 to 0.13) at age 15. Conclusions This longitudinal study revealed that children presenting a long sleep latency throughout childhood are at greater risk of symptoms of depression, ADHD, conduct problems, and opposition in adolescence

Design, Synthesis, Biological Evaluation, and Structure–Activity Relationships of Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)benzenesulfonates as New Tubulin Inhibitors Mimicking Combretastatin A-4

International audienc

Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation

Background: Anoikis resistance is one of the abilities acquired along tumor progression. This characteristic is associated with metastasis development, since tumorigenic cells must survive independently of cell-matrix interactions in this process. in our laboratory, it was developed a murine melanocyte malignant transformation model associated with a sustained stressful condition. After subjecting melan-a melanocytes to 1, 2, 3 and 4 cycles of anchorage impediment, anoikis resistant cells were established and named 1C, 2C, 3C and 4C, respectively. These cells showed altered morphology and PMA independent cell growth, but were not tumorigenic, corresponding to pre-malignant cells. After limiting dilution of 4C pre-malignant cells, melanoma cell lines with different characteristics were obtained. Previous data from our group showed that increased Timp1 expression correlated with anoikis-resistant phenotype. Timp1 was shown to confer anchorage-independent growth capability to melan-a melanocytes and render melanoma cells more aggressive when injected into mice. However, the mechanisms involved in anoikis regulation by Timp1 in tumorigenic cells are not clear yet.Methods: the beta 1-integrin and Timp1 expression were evaluated by Western blotting and CD63 protein expression by flow cytometry using specific antibodies. To analyze the interaction among Timp1, CD63 and beta 1-integrin, immunoprecipitation assays were performed, anoikis resistance capability was evaluated in the presence or not of the PI3-K inhibitors, Wortmannin and LY294002. Relative expression of TIMP1 and CD63 in human metastatic melanoma cells was analyzed by real time PCR.Results: Differential association among Timp1, CD63 and beta 1-integrins was observed in melan-a melanocytes, 4C pre-malignant melanocytes and 4C11- and 4C11+ melanoma cells. Timp1 present in conditioned medium of melanoma cells rendered melan-a melanocytes anoikis-resistant through PI3-K signaling pathway independently of Akt activation. in human melanoma cell lines, in which TIMP1 and beta-1 integrin were also found to be interacting, TIMP1 and CD63 levels together was shown to correlate significantly with colony formation capacity.Conclusions: Our results show that Timp1 is assembled in a supramolecular complex containing CD63 and beta 1-integrins along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway, independently of Akt phosphorylation. in addition, our data point TIMP1, mainly together with CD63, as a potential biomarker of melanoma.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilLudwig Inst Canc Res, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilFAPESP: 2011/12306-1FAPESP: 2010/18715-8CAPES: 2867/10Web of Scienc

Angiogenesis and chronic kidney disease

The number of patients requiring renal replacement therapy due to end-stage renal disease (ESRD) is increasing worldwide. The prevalence of chronic kidney disease (CKD), and the importance of CKD as a risk factor in development of ESRD and in complicating cardiovascular disease (CVD) have been confirmed. In recent years, the involvement of angiogenesis-related factors in the progression of CKD has been studied, and the potential therapeutic effects on CKD of modulating these factors have been identified. Vascular endothelial growth factor (VEGF)-A, a potent pro-angiogenic factor, is involved in the development of the kidney, in maintenance of the glomerular capillary structure and filtration barrier, and in the renal repair process after injury. VEGF-A is also involved in the development of early diabetic nephropathy, demonstrated by the therapeutic effects of anti-VEGF-A antibody. Angiopoietin (Ang)-1 induces the maturation of newly formed blood vessels, and the therapeutic effects of Ang-1 in diabetic nephropathy have been described. In experimental models of diabetic nephropathy, the therapeutic effects of angiogenesis inhibitors, including angiostatin, endostatin and tumstatin peptides, the isocoumarin NM-3, and vasohibin-1, have been reported