Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis by Downregulating Inflammation and Th1 Response

Poly(ADP-ribose) polymerase-1 (PARP-1) synthesizes and transfers ADP ribose polymers to target proteins, and regulates DNA repair and genomic integrity maintenance. PARP-1 also plays a crucial role in the progression of the inflammatory response, and its inhibition confers protection in several models of inflammatory disorders. Here, we investigate the impact of a selective PARP-1 inhibitor in experimental arthritis. PARP-1 inhibition with 5-aminoisoquinolinone (AIQ) significantly reduces incidence and severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of AIQ is associated with a striking reduction of the two deleterious components of the disease, i.e. the Th1-driven autoimmune and inflammatory responses. AIQ downregulates the production of various inflammatory cytokines and chemokines, decreases the antigen-specific Th1-cell expansion, and induces the production of the anti-inflammatory cytokine IL-10. Our results provide evidence of the contribution of PARP-1 to the progression of arthritis and identify this protein as a potential therapeutic target for the treatment of rheumatoid arthritis

Self-reported sleep duration, white blood cell counts and cytokine profiles in European adolescents: the HELENA study.

sleep duration, inflammation, HELEN

Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain

All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.Spanish Ministry of Economy and Competitiveness and European FEDER funds (grant number BFU2014-57516-P). To Luis Puelles and Jose Luis Ferran. European Research Council (grant number ERC-StG-LS2-637591). To Manuel Irimia. Spanish Ministry of Economy and Competitiveness (grant number SEV-2012-0208).Centro de Excelencia Severo Ochoa (to CRG, Manuel Irimia). Spanish Ministry of Economy and Competitiveness (grant number BFU2014-58908-P). To Jordi Garcia-Fernadez. Seneca Foundation, Comunidad de Murcia (grant number 19904/GERM/15). To Luis Puelles. Generalitat de Catalunya (grant number). ICREA Academia Prize to Jordi Garcia-Fernandez. Spanish Ministry of Economy and Competitiveness (grant number BFU2013-43213-P). To Paola Bovolenta. Spanish Ministry of Economy and Competitiveness (grant number BFU2014-55076-P). To Manuel Irimia. Including an FPI PhD fellowship to Laura Lopez-Blanch. Marine Alliance for Science and Technology Scotland (MASTS) (grant number). To Ildiko Somorjai

Socioeconomic status influences physical fitness in European adolescents independently of body fat and physical activity: the HELENA study

The influence of socioeconomic status on health-related fitness is not clear

Attenuation of the effect of the FTO rs9939609 polymorphism on total and central body fat by physical activity in adolescents: the HELENA study

To examine whether physical activity attenuates the effect of the FTO rs9939609 polymorphism on body fat estimates in adolescents