Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis

CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice) indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II) immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA). We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT) cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses

Pro-Inflammatory Cytokine Induction of 11β-hydroxysteroid Dehydrogenase Type 1 in A549 Cells Requires Phosphorylation of C/EBPβ at Thr235

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inert glucocorticoids into active forms, thereby increasing intracellular glucocorticoid levels, important to restrain acute inflammation. 11β-HSD1 is induced by pro-inflammatory cytokines in a variety of cells. Here, we show 11β-HSD1 expression in human A549 epithelial cells is increased by pro-inflammatory cytokines (IL-1α/TNFα) via the P2 promoter of the HSD11B1 gene. Inhibition of p38 MAPK attenuated the pro-inflammatory cytokine induction of mRNA encoding 11β-HSD1 as well as that encoding C/EBPβ. IL-1α/TNFα-induced phosphorylation of C/EBPβ at Thr235 was also attenuated by p38 MAPK inhibition suggesting involvement of a p38 MAPK-C/EBPβ pathway. siRNA-mediated knock-down of C/EBPβ and NF-κB/RelA implicated both transcription factors in the IL-1α/TNFα induction of HSD11B1 mRNA. Transient transfections of HSD11B1 promoter-reporter constructs identified the proximal region of the P2 promoter of HSD11B1 as essential for this induction. IL-1α increased binding of C/EBPβ to the HSD11B1 P2 promoter, but this was not observed for NF-κB/RelA, suggesting indirect regulation by NF-κB/RelA. Ectopic expression of mutant chicken C/EBPβ constructs unable to undergo phosphorylation at the threonine equivalent to Thr235 attenuated the IL-1α-induction of HSD11B1, whereas mimicking constitutive phosphorylation of Thr235 (by mutation to aspartate) increased basal expression of HSD11B1 mRNA without affecting IL-1α-induced levels. These data clearly demonstrate a role for both C/EBPβ and NF-κB/RelA in the pro-inflammatory cytokine induction of HSD11B1 in human epithelial cells and show that p38 MAPK-induced phosphorylation of C/EBPβ at Thr235 is critical in this

The Wide-field Spectroscopic Telescope (WST) Science White Paper

The Wide-field Spectroscopic Telescope (WST) is proposed as a new facility dedicated to the efficient delivery of spectroscopic surveys. This white paper summarises the initial concept as well as the corresponding science cases. WST will feature simultaneous operation of a large field-of-view (3 sq. degree), a high multiplex (20,000) multi-object spectrograph (MOS) and a giant 3x3 sq. arcmin integral field spectrograph (IFS). In scientific capability these requirements place WST far ahead of existing and planned facilities. Given the current investment in deep imaging surveys and noting the diagnostic power of spectroscopy, WST will fill a crucial gap in astronomical capability and work synergistically with future ground and space-based facilities. This white paper shows that WST can address outstanding scientific questions in the areas of cosmology; galaxy assembly, evolution, and enrichment, including our own Milky Way; origin of stars and planets; time domain and multi-messenger astrophysics. WST's uniquely rich dataset will deliver unforeseen discoveries in many of these areas. The WST Science Team (already including more than 500 scientists worldwide) is open to the all astronomical community. To register in the WST Science Team please visit https://www.wstelescope.com/for-scientists/participat

Atividade física no lazer, deslocamento, apoio social e percepção do ambiente urbano em homens e mulheres de Florianópolis/SC

The aim of the study was to identify characteristics of the perceived physical environment and social support associated with physical activity during leisure (LFA), and transportation (TFA) in man and women. The study was based on a systematic sample of 746 residents in Florianópolis, SC, Brazil, obtained by phonebook. We utilized the long version of International Physical Activity Questionnaire (IPAQ), and the scale of active mobility in the community environment (news adapted). The outcomes investigated were not meeting the recommendations for physical activity (NARAF) in LFA and TFA in man and women. As explanatory variables we investigated the characteristics of socio-demographic variables, perception of the environment, general health, and body mass index (IMC). We performed logistic regression analysis to estimate the odds ratios and the adjusted attributes of the physical environment and social support of man and women that NARAF. The response rate was 91% (n = 746). The prevalence of women in NARAF in transportation was 73.3% (69.1-77.5%) and for men was 71.1% (66.1 to 76.2%). In the LFA NARAF prevalence of women was 78.4% (74.5-78.3%) and 74.9% (70.1-79.7%) in men. In TFA environmental attributes associated with less chance of NARAF were: live in an area close to shopping areas, gym and bank branch close to home. In the LFA, street lighting, security during the day, walking site close to home and live near the coastline. Programs to promote AFL in adults should consider variables of the urban environment (lit streets, safety, local walking or physical activity and attractiveness of locations). To promote the TFA should be considered public and private structures (proximity to shopping areas, gyms, banks and attractiveness of locations).O objetivo do estudo foi identificar características do ambiente físico e social percebido associadas à atividade física no lazer (AFL) e deslocamento (AFD) em homens e mulheres. Amostra sistemética de 746 pessoas residentes em Florianópolis/SC obtida por lista telefônica. Utilizou-se o questionário internacional de atividade física [IPAQ) versão longa e o questionário da escala de mobilidade ativa no ambiente comunitário “news” adaptado. Os desfechos investigados foram: não atender as recomendações em relação à atividade física (NARAF) nas AFL e AFD em homens e mulheres. Como variáveis exploratórias foram investigadas as caracteristícas das variáveis sócio-demográficas, percepção do ambiente, saúde gerai e índice de massa corporal. Foi realizada análise de regressão logística para estimar as razões de chance bruta e ajustada dos atributos do ambiente físico e apoio social das pessoas que NARAF. Ataxa de resposta foi de 91% (n = 746). A prevalência de mulheres que NARAF no deslocamento foi de 73,3% (69,1-77,5%) e a de homens de 71,1% (66,1-76,2%). Nas AFL a prevalência de mulheres que NARAF foi de 78,4% (74,5-78,3%) e a de homens de 74,9% (70,1-79,7%). Nas AFD os atributos do ambiente associados a menos chance de NARAF foram: morar em área próxima ao comércio; academia e agênda bancária próximo de casa. Nas AFL, ruas iluminadas, segurança durante o dia, local para caminhar próximo de casa e morar próximo à orla marítima. Programas de promoção de AFL em adultos devem considerar variáveis do ambiente urbano (ruas iluminadas, segurança, local para caminhar ou praticar atividade física e a atratividade dos locais). Para promover as AFD devem ser consideradas as estruturas públicas e privadas (proximidade dos centros de compra, academias, agêndas bancárias e atratividade dos locais)