Raman spectroscopic study on the conformation of 11 S form acetylcholinesterase from Torpedo californica

AbstractVibrational Raman spectroscopy has been used to study the conformation of the 11 S form of acetylcholine-sterase from Torpedo californica. Secondary structure analysis by the method of Williams [(1983) J. Mol. Biol. 166, 581–603] shows 49% α-helical structure, 23% β-sheets, 11% turns and 15% undefined structure. Secondary structure estimates obtained for this enzyme by Raman spectroscopy and circular dichroism have been analyzed

Robert F. Furchgott, Nobel laureate (1916-2009) - a personal reflection

Robert F. Furchgott, pharmacologist and joint winner of the Nobel Prize for Medicine or Physiology (1998) died on the 12th of May 2009 aged 92. By unlocking the astonishingly diverse biological actions of nitric oxide, Furchgott leaves behind a rich legacy that has both revolutionized our understanding of human physiology and stimulated new and exciting opportunities for drug development in a wide range of pathological conditions. In this article, William Martin, who worked with Furchgott for 2 years (1983-1985), following the exciting discovery of endothelium-derived relaxing factor/nitric oxide, pays tribute to his close friend and colleague

Does ratification of human-rights treaties have effects on population health?

Human-rights treaties indicate a country's commitment to human rights. Here, we assess whether ratification of human-rights treaties is associated with improved health and social indicators. Data for health (including HIV prevalence, and maternal, infant, and child [<5 years] mortalities) and social indicators (child labour, human development index, sex gap, and corruption index), gathered from 170 countries, showed no consistent associations between ratification of human-rights treaties and health or social outcomes. Established market economy states had consistently improved health compared with less wealthy settings, but this was not associated with treaty ratification. The status of treaty ratification alone is not a good indicator of the realisation of the right to health. We suggest the need for stringent requirements for ratification of treaties, improved accountability mechanisms to monitor compliance of states with treaty obligations, and financial assistance to support the realisation of the right to health

Delayed resolution of acute inflammation during zymosan-induced arthritis in leptin-deficient mice

The severity of antigen-induced arthritis (AIA) is decreased in leptin-deficient ob/ob mice. However, joint inflammation in AIA depends on the immune response, which is impaired in ob/ob mice. In the present study we investigated the effects of leptin deficiency on zymosan-induced arthritis (ZIA), which is independent of adaptive immunity. Arthritis was induced by injection of zymosan into the knee joint. Joint swelling was similar after 6 and 24 hours in ob/ob and control mice. However, it remained elevated in ob/ob animals on day 3 whereas values normalized in controls. Histology revealed similar articular lesions in all animals on day 3, but on days 14 and 21 arthritis tended to be more severe in ob/ob mice. The acute phase response, reflected by circulating levels of IL-6 and serum amyloid A, was also more pronounced in ob/ob mice, although corticosterone was significantly elevated in these animals. Similar results were obtained in leptin receptor-deficient db/db mice. Thus, in contrast to AIA, ZIA is not impaired in leptin-deficient animals. On the contrary, resolution of acute inflammation appears to be delayed in the absence of leptin or leptin signalling, suggesting that chronic leptin deficiency interferes with adequate control of the inflammatory response in ZIA

The active metabolite of leflunomide, A77 1726, increases the production of IL-1 receptor antagonist in human synovial fibroblasts and articular chondrocytes

Leflunomide is an immunomodulatory agent used for the treatment of rheumatoid arthritis. In this study, we investigated the effect of A77 1726 – the active metabolite of leflunomide – on the production of IL-1 receptor antagonist (IL-1Ra) by human synovial fibroblasts and articular chondrocytes. Cells were incubated with A77 1726 alone or in combination with proinflammatory cytokines. IL-1Ra production was determined by ELISA. A77 1726 alone had no effect, but in the presence of IL-1β or tumour necrosis factor-α it markedly enhanced the secretion of IL-1Ra in synovial fibroblasts and chondrocytes. The effect of A77 1726 was greatest at 100 μmol/l. In synovial fibroblasts and de-differentiated chondrocytes, A77 1726 also increased IL-1β-induced IL-1Ra production in cell lysates. Freshly isolated chondrocytes contained no significant amounts of intracellular IL-1Ra. A77 1726 is a known inhibitor of pyrimidine synthesis and cyclo-oxygenase (COX)-2 activity. Addition of exogenous uridine did not significantly modify the effect of A77 1726 on IL-1Ra production, suggesting that it was not mediated by inhibition of pyrimidine synthesis. Indomethacin increased IL-1β-induced IL-1Ra secretion in synovial fibroblasts and de-differentiated chondrocytes, suggesting that inhibition of COX-2 may indeed enhance IL-1β-induced IL-1Ra production. However, the stimulatory effect of indomethacin was consistently less effective than that of A77 1726. A77 1726 increases IL-1Ra production by synovial fibroblasts and chondrocytes in the presence of proinflammatory cytokines, and thus it may possess chondroprotective effects. The effect of A77 1726 may be partially mediated by inhibition of COX-2, but other mechanisms likely concur to stimulate IL-1Ra production

Magnetars From Magnetized Cores Created by a Strong Interaction Phase Transition

We consider a model where the strong magnetic fields of magnetars arise from a high baryon density, magnetized core. In this framework magnetars are distinguished from pulsars by their higher masses and central density. For magnetars, as core densities exceed a threshold, the strong interaction induces a phase transition to a neutral pion condensate that aligns all magnetic moments. The core magnetic field is initially shielded by the ambient high conductivity plasma. With time the shielding currents dissipate transporting the core field out, first to the crust and then breaking through the crust to the surface of the star. Recent observations provide strong support for this model which accounts for several properties of magnetars and also enables us to identify new magnetars.Comment: 22 pages with 3 figures and 3 tables prepared in 'Science' forma

Expression and function of junctional adhesion molecule-C in human and experimental arthritis

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule involved in transendothelial migration of leukocytes. In this study, we examined JAM-C expression in the synovium and investigated the role of this molecule in two experimental mouse models of arthritis. JAM-C expression was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The effects of a monoclonal anti-JAM-C antibody were assessed in antigen-induced arthritis (AIA) and K/BxN serum transfer-induced arthritis. JAM-C was expressed by synovial fibroblasts in the lining layer and associated with vessels in the sublining layer in human and mouse arthritic synovial tissue. In human tissue, JAM-C expression was increased in rheumatoid arthritis (RA) as compared to osteoarthritis synovial samples (12.7 ± 1.3 arbitrary units in RA versus 3.3 ± 1.1 in OA; p < 0.05). Treatment of mice with a monoclonal anti-JAM-C antibody decreased the severity of AIA. Neutrophil infiltration into inflamed joints was selectively reduced as compared to T-lymphocyte and macrophage infiltration (0.8 ± 0.3 arbitrary units in anti-JAM-C-treated versus 2.3 ± 0.6 in isotype-matched control antibody-treated mice; p < 0.05). Circulating levels of the acute-phase protein serum amyloid A as well as antigen-specific and concanavalin A-induced spleen T-cell responses were significantly decreased in anti-JAM-C antibody-treated mice. In the serum transfer-induced arthritis model, treatment with the anti-JAM-C antibody delayed the onset of arthritis. JAM-C is highly expressed by synovial fibroblasts in RA. Treatment of mice with an anti-JAM-C antibody significantly reduced the severity of AIA and delayed the onset of serum transfer-induced arthritis, suggesting a role for JAM-C in the pathogenesis of arthritis

Building an ontology of cardio-vascular diseases for concept-based information retrieval

International audienc

Animal models of intrauterine growth retardation of vascular origin

Placental insufficiencies can complicate up to 7% of all pregnancies. They can lead to intrauterine growth retardation (IUGR) and preeclampsia, and represent a major public health concern. The pathophysiology of these placental anomalies is not yet fully understood. For obvious ethical reasons, studies in pregnant women are limited to non-invasive techniques, such as ultrasound scans and maternal blood tests. Therefore, animal models of IUGR play an important role in the study of this condition. Because the models using maternal undernutrition to induce foetal IUGR are not as appropriate to mimic the vascular IUGR observed in developed countries, we describe the animal models of vascular IUGR used currently: models based on an application of stress to the mother, genetic models, and surgical models. Finally, we describe briefly the controlled hypoperfusion model in non-anaesthetized ewes, currently developed in our laboratory.Les défauts de perfusion placentaire compliquent environ 7 % des grossesses. Ils peuvent entraîner un retard de croissance intra-utérin (RCIU) et une pré-éclampsie, et posent un problème majeur de santé publique. La physiopathologie de ces défauts n'est pas totalement connue. Les études chez la femme sont limitées à des examens non invasifs, échographiques et biologiques, pour des raisons éthiques évidentes. Il est donc important de disposer de modèles animaux expérimentaux pour appréhender cette pathologie. Nous n'abordons pas ici les modèles de sous-nutrition maternelle, qui ne nous semblent pas complètement appropriés pour reproduire les aspects physiopathologiques observés dans les pays développés. Les modèles animaux de RCIU d'origine vasculaire jusqu'ici utilisés sont décrits: modèles basés sur l'application d'un stress à la mère, modèles génétiques et modèles chirurgicaux. Enfin. Nous décrivons aussi brièvement le modèle d'hypoperfusion contrôlée chez la brebis vigile, actuellement mis au point au laboratoire