Differences in receptivity to gastrointestinal infections with nematodes in dairy ewes: Influence of age and of the level of milk production

Resistance to anthelmintics in populations of gastrointestinal nematodes is a major concern in small ruminants. One solution to limit the spread of anthelmintic resistance is to apply treatments selectively by targeting the most susceptible animals within a flock. In dairy goats, previous studies have shown that, within a flock, goats in first lactation and those with high level of milk production were highly receptive to nematode infections. These results provided the rationale for targeted treatments. In dairy ewes, such epidemiological information on possible factors modulating the susceptibility to parasitism were still lacking. The objective of the current study was therefore to examine differences in the level of parasite infection and in the pathophysiological consequences in dairy ewes, depending on the age or on the level of milk production. In three farms, parasite egg excretion, and the serum concentrations of pepsinogen and inorganic phosphate were compared on one hand between primiparous and multiparous ewes; on the other hand, between ewes with the highest and the lowest level of milk production, within a cohort of 3–5-year old animals. Overall, the results did not indicate significant differences for both either the parasitological or pathophysiological measurements depending on the level of milk production. In contrast, significant differences were found according to age, indicating higher levels of infections in the primiparous ewes than in the multiparous ones and suggesting that this category of animals represents a particular parasitic risk within a flock

Optimal Operation of the Multireservoir System in the Seine River Basin Using Deterministic and Ensemble Forecasts

International audienceThis article investigates the improvement of the operation of a four-reservoir system in the Seine River basin, France, by use of deterministic and ensemble weather forecasts and real-time control. In the current management, each reservoir is operated independently from the others and following prescribed rule-curves, designed to reduce floods and sustain low flows under the historical hydrological conditions. However, this management system is inefficient when inflows are significantly different from their seasonal average and may become even more inadequate to cope with the predicted increase in extreme events induced by climate change. In this work, a centralized real-time control system is developed to improve reservoirs operation by exploiting numerical weather forecasts that are becoming increasingly available. The proposed management system implements a well-established optimization technique, model predictive control (MPC), and its recently modified version that can incorporate uncertainties, tree-based model predictive control (TB-MPC), to account for deterministic and ensemble forecasts respectively. The management system is assessed by simulation over historical events and compared to the no-forecasts strategy based on rule-curves. Simulation results show that the proposed real-time control system largely outperforms the no-forecasts management strategy, and that explicitly considering forecast uncertainty through ensembles can compensate for the loss in performance due to forecast inaccuracy

Farnesoid X Receptor and its ligands inhibit the function of platelets

Objective - While initially seemingly paradoxical due to the lack of nucleus, platelets possess a number of transcription factors that regulate their function through DNA-independent mechanisms. These include the Farnesoid X Receptor (FXR), a member of the superfamily of ligand-activated transcription factors that has been identified as a bile acid receptor. In this study, we show that FXR is present in human platelets and FXR ligands, GW4064 and 6-ECDCA, modulate platelet activation nongenomically. Approach and Results - FXR ligands inhibited the activation of platelets in response to stimulation of collagen or thrombin receptors, resulting in diminished intracellular calcium mobilization and secretion, fibrinogen binding and aggregation. Exposure to FXR ligands also reduced integrin alphaIIbbeta3 outside-in signaling and thereby reduced the ability of platelets to spread and to stimulate clot retraction. FXR function in platelets was found to be associated with the modulation of cGMP levels in platelets and associated downstream inhibitory signaling. Platelets from FXR-deficient mice were refractory to the actions of FXR agonists on platelet function and cyclic nucleotide signaling, firmly linking the non-genomic actions of these ligands to the FXR receptor. Conclusion – This study provides support for the ability of FXR ligands to modulate platelet activation. The athero-protective effects of GW4064, with its novel antiplatelet effects, indicate FXR as a potential target for prevention of athero-thrombotic disease

Quantitative evaluation of the beneficial effects in the mdx mouse of epigallocatechin gallate, an antioxidant polyphenol from green tea

In two separate previous studies, we reported that subcutaneous (sc) or oral administration of (−)-epigallocatechin-3-gallate (EGCG) limited the development of muscle degeneration of mdx mice, a mild phenotype model for Duchenne muscular dystrophy (DMD). However, it was not possible to conclude which was the more efficient route of EGCG administration because different strains of mdx mice, periods of treatment and methods of assessment were used. In this study, we investigated which administration routes and dosages of EGCG are the most effective for limiting the onset of dystrophic lesions in the same strain of mdx mice and applying the same methods of assessment. Three-week-old mdx mice were injected sc for 5 weeks with either saline or a daily average of 3 or 6 mg/kg EGCG. For comparison, age-matched mdx mice were fed for 5 weeks with either a diet containing 0.1% EGCG or a control diet. The effects of EGCG were assessed quantitatively by determining the activities of serum muscle-derived creatine kinase, isometric contractions of triceps surae muscles, integrated spontaneous locomotor activities, and oxidative stress and fibrosis in selected muscles. Oral administration of 180 mg/kg/day EGCG in the diet was found the most effective for significantly improving several parameters associated with muscular dystrophy. However, the improvements were slightly less than those observed previously for sc injection started immediately after birth. The efficacy of EGCG for limiting the development of dystrophic muscle lesions in mice suggests that EGCG may be of benefit for DMD patients

Towards the european strategy for particle physics: The briefing book

This document was prepared as part of the briefing material for the Workshop of the CERN Council Strategy Group, held in DESY Zeuthen from 2nd to 6th May 2006. It gives an overview of the physics issues and of the technological challenges that will shape the future of the field, and incorporates material presented and discussed during the Symposium on the European Strategy for Particle Physics, held in Orsay from 30th January to 2nd February 2006, reflecting the various opinions of the European community as recorded in written submissions to the Strategy Group and in the discussions at the Symposium

Skeletal Muscle NADPH Oxidase Is Increased and Triggers Stretch-Induced Damage in the mdx Mouse

Recent studies have shown that oxidative stress contributes to the pathogenesis of muscle damage in dystrophic (mdx) mice. In this study we have investigated the role of NADPH oxidase as a source of the oxidative stress in these mice. The NADPH oxidase subunits gp91phox, p67phox and rac 1 were increased 2–3 fold in tibilais anterior muscles from mdx mice compared to wild type. Importantly, this increase occurred in 19 day old mice, before the onset of muscle necrosis and inflammation, suggesting that NADPH oxidase is an important source of oxidative stress in mdx muscle. In muscles from 9 week old mdx mice, gp91phox and p67phox were increased 3–4 fold and NADPH oxidase superoxide production was 2 times greater than wild type. In single fibers from mdx muscle NADPH oxidase subunits were all located on or near the sarcolemma, except for p67phox,which was expressed in the cytosol. Pharmacological inhibition of NADPH oxidase significantly reduced the intracellular Ca2+ rise following stretched contractions in mdx single fibers, and also attenuated the loss of muscle force. These results suggest that NADPH oxidase is a major source of reactive oxygen species in dystrophic muscle and its enhanced activity has a stimulatory effect on stretch-induced Ca2+ entry, a key mechanism for muscle damage and functional impairment