Intracellular Ca2+ release through ryanodine receptors contributes to AMPA receptor-mediated mitochondrial dysfunction and ER stress in oligodendrocytes

Overactivation of ionotropic glutamate receptors in oligodendrocytes induces cytosolic Ca2+ overload and excitotoxic death, a process that contributes to demyelination and multiple sclerosis. Excitotoxic insults cause well-characterized mitochondrial alterations and endoplasmic reticulum (ER) dysfunction, which is not fully understood. In this study, we analyzed the contribution of ER-Ca2+ release through ryanodine receptors (RyRs) and inositol triphosphate receptors (IP(3)Rs) to excitotoxicity in oligodendrocytes in vitro. First, we observed that oligodendrocytes express all previously characterized RyRs and IP(3)Rs. Blockade of Ca2+-induced Ca2+ release by TMB-8 following alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor-mediated insults attenuated both oligodendrocyte death and cytosolic Ca2+ overload. In turn, RyR inhibition by ryanodine reduced as well the Ca2+ overload whereas IP3R inhibition was ineffective. Furthermore, AMPA-triggered mitochondrial membrane depolarization, oxidative stress and activation of caspase-3, which in all instances was diminished by RyR inhibition. In addition, we observed that AMPA induced an ER stress response as revealed by alpha subunit of the eukaryotic initiation factor 2 alpha phosphorylation, overexpression of GRP chaperones and RyR-dependent cleavage of caspase-12. Finally, attenuating ER stress with salubrinal protected oligodendrocytes from AMPA excitotoxicity. Together, these results show that Ca2+ release through RyRs contributes to cytosolic Ca2+ overload, mitochondrial dysfunction, ER stress and cell death following AMPA receptor-mediated excitotoxicity in oligodendrocytes. Cell Death and Disease (2010) 1, e54; doi:10.1038/cddis.2010.31; published online 15 July 2010

How central are clients in sexual networks created by commercial sex?

Sex workers are traditionally considered important vectors of transmission of sexually transmitted infections (STI). The role of clients is commonly overlooked, partially due to the lack of evidence on clients' position in the sexual network created by commercial sex. Contrasting the diffusion importance of sex workers and their clients in the map of their sexual encounters in two Web-mediated communities, we find that from diffusion perspective, clients are as important as sex workers. Their diffusion importance is closely linked to the geography of the sexual encounters: as a result of different movement patterns, travelling clients shorten network distances between distant network neighborhoods and thus facilitate contagion among them more than sex workers, and find themselves more often in the core of the network by which they could contribute to the persistence of STIs in the community. These findings position clients into the set of the key actors and highlight the role of human mobility in the transmission of STIs in commercial sexual networks.

El tratamiento por parte de Naciones Unidas de la violación sexual a mujeres en los conflictos armados: las guerras en los Balcanes

32 p.

El “círculo victimal” en la victimización sexual infantil

Mediante este estudio nos hemos acercado a la victimización sexual infantil desde el concepto de “círculo víctimal”. Tras una contextualización en la que realizamos una revisión de la bibliografía más relevante desde la óptica adoptada, presentamos nuestro propio trabajo de campo con datos de Gipuzkoa. Se han analizado un total de 51 sentencias, principalmente condenatorias, emitidas tanto por la Audiencia Provincial de Gipuzkoa como por el Juzgado de Menores de San Sebastián –incluyendo en este caso no sólo sentencias sino también expedientes-. El periodo abarcado han sido los años 2004-2014. Dicho análisis nos ha permitido considerar las características del abuso, de la víctima y del agresor, el posible impacto victimal, así como la existencia o no de antecedentes de abusos en la infancia en la vida de los agresores. Los resultados se han contrastado con los estudios teóricos y empíricos de ámbito internacional referentes al “círculo victimal” en el ámbito de los abusos sexuales infantiles, deteniéndonos especialmente en si la víctima fue abusada en la familia o fuera de ella y si se convierte en abusador de su propia familia o de alguien fuera de ella. Adicionalmente, con el objeto de introducir la voz de los propios protagonistas, a través de fuentes secundarias, se han rescatado historiales de agresores de menores con antecedentes de abusos. Asimismo se ha completado el trabajo de campo con entrevistas a expertos.