B cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation

Studies in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), have shown that regulatory B cells modulate the course of the disease via the production of suppressive cytokines. While data indicate a role for transforming growth factor (TGF)-β1 expression in regulatory B cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B-TGF-β1(-/-)) were tested in EAE induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG). In this model, B-TGF-β1(-/-) mice showed an earlier onset of neurologic impairment compared to their littermate controls. Exacerbated EAE susceptibility in B-TGF-β1(-/-) mice was associated with augmented CNS T helper (Th)1/17 responses. Moreover, selective B cell TGF-β1-deficiency increased the frequencies and activation of myeloid dendritic cells, potent professional antigen-presenting cells (APCs), suggesting that B cell-derived TGF-β1 can constrain Th1/17 responses through inhibition of APC activity. Collectively our data suggest that B cells can down-regulate the function of APCs, and in turn encephalitogenic Th1/17 responses, via TGF-β1, findings that may be relevant to B cell-targeted therapies

Immunologic monitoring during a phase 2a trial of the GNbAC1 antibody in patients with MS.

To monitor the systemic immune responses of patients with multiple sclerosis (MS) under treatment with GNbAC1, a monoclonal antibody against the envelope protein of the MS- associated retrovirus, during a phase 2a trial

Travail, temps libre et domaines d'épanouissement chez les mères de famille: Comparaison entre les mères de familles monoparentales et biparentales

La famille est conceptualisée comme entre l'individu et la société: des différences dans la structure familiale impliquent des modes différents d'articulation de ses membres au niveau sociétal. Ainsi, les mères de familles monoparentales ne sont pas que des mères sans conjoint; ce statut familial a des implications sur leur rapport à l'activité et sur leur position sociale. Le modèle adopté pour l'étude d'un échantillon suisse de 8923 mères (dont 600 chefs de familles monoparentales) inclut en conséquence des paramètres familiaux et des paramètres sociétaux. Les résultats attestent la pertinence du modèle d'analyse et mettent en évidence le caractère fallacieux d'un modèle limité aux variables familiales. Ainsi, par exemple, c'est l'activité des mères qui détermine principalement leur évaluation des temps sociaux et non pas le conjoint pris en soi. En revanche, la présence ou l'absence de ce dernier oriente de manière substantielle la quête d'épanouissement des mères.The family is conceived of as a link between society and the individual. The various types of relationships between the family members and the society mirror the differences within the family structure. Thus, single mothers are not only mothers without a partner; this status impacts on their attitude towards work and on their social position. The study of a sample of 8923 Swiss mothers (including 600 single household heads) therefore encompasses family and social parameters. The findings support the validity of the theoretical construct, and show that an approach limited to family variables would be misleading. For example, a mother's evaluation of social times depends mainly on her work load rather than on her partner. On the other hand, the latter's presence or absence has a major impact on her positive attitudes towards life.La familia está conceptualizada como el punto medio entre el individuo y la sociedad: diferencias en la estructura familiar implican modos diferentes de articulación de sus miembros al nivel de la sociedad. De esta manera las madres de familia solas (o madres solteras) no es otra cosa que las madres sin cónyuge; esta categoría familiar tiene implicaciones en su actitud hacia las actividades y a su posición social. El modelo adoptado por el estudio de una muestra de 8923 madres suizas (entre ellas 600 madres solas jefes de familia), incluye la importancia de los parámetros familiares y de los parámetros sociales. Los resultados testimonian la pertinencia del modelo de análisis y ponen en evidencia el caraácter falaz de un modelo limitado a las variables familiares. Así, por ejemplo, es la actividad de las madres la que determina principalmente su evaluación del tiempo social y no su cónyuge, si éste se toma en cuenta. En cambio la presencia o la ausencia de un cónyuge orienta de manera substancial la búsqueda de la satisfacción de las madres

The trend in sport participation among Dutch retirees, 1983-2007

Contains fulltext : 116741.pdf (publisher's version ) (Closed access)This paper investigates the trend in sport participation among retirees between 1983 and 2007. Sport participation is important for retirees because of its health benefits and the opportunities it offers for social interaction. Factors that influence sport participation such as educational level, physical limitations, and occupational background have changed during the last decades, possibly accounting for changes in sport participation. Data are from the Amenities and Services Utilization Survey (AVO), a nationally representative Dutch survey with seven observations between 1983 and 2007. The trend in sport involvement, sports club membership, and competition was investigated in a sample of 2,497 male and 1,559 female retirees aged 58–67 years. Increases in participation were observed in sport involvement and sports club membership. This trend can partially be explained by increases in educational level, decreases in the number of retirees with physical limitations, and in those retiring from sedentary jobs. Yet, sport participation seems to have increased for all retirees, regardless of their socio-economic background and health status. Alternative explanations for the observed trend are discussed

Methamphetamine-evoked depression of GABA(B) receptor signaling in GABA neurons of the VTA.

Psychostimulants induce neuroadaptations in excitatory and fast inhibitory transmission in the ventral tegmental area (VTA). Mechanisms underlying drug-evoked synaptic plasticity of slow inhibitory transmission mediated by GABA(B) receptors and G protein-gated inwardly rectifying potassium (GIRK/Kir(3)) channels, however, are poorly understood. Here, we show that 1 day after methamphetamine (METH) or cocaine exposure both synaptically evoked and baclofen-activated GABA(B)R-GIRK currents were significantly depressed in VTA GABA neurons and remained depressed for 7 days. Presynaptic inhibition mediated by GABA(B)Rs on GABA terminals was also weakened. Quantitative immunoelectron microscopy revealed internalization of GABA(B1) and GIRK2, which occurred coincident with dephosphorylation of serine 783 (S783) in GABA(B2), a site implicated in regulating GABA(B)R surface expression. Inhibition of protein phosphatases recovered GABA(B)R-GIRK currents in VTA GABA neurons of METH-injected mice. This psychostimulant-evoked impairment in GABA(B)R signaling removes an intrinsic brake on GABA neuron spiking, which may augment GABA transmission in the mesocorticolimbic system