Mast cell tryptase stimulates myoblast proliferation; a mechanism relying on protease-activated receptor-2 and cyclooxygenase-2

<p>Abstract</p> <p>Background</p> <p>Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2). The possibility that a tryptase/PAR-2 signaling pathway exists in skeletal muscle cell has never been investigated. The aim of this study was to evaluate whether tryptase can stimulate myoblast proliferation and determine the downstream cascade.</p> <p>Methods</p> <p>Proliferation of L6 rat skeletal myoblasts stimulated with PAR-2 agonists (tryptase, trypsin and SLIGKV) was assessed. The specificity of the tryptase effect was evaluated with a specific inhibitor, APC-366. Western blot analyses were used to evaluate the expression and functionality of PAR-2 receptor and to assess the expression of COX-2. COX-2 activity was evaluated with a commercial activity assay kit and by measurement of PGF₂α production. Proliferation assays were also performed in presence of different prostaglandins (PGs).</p> <p>Results</p> <p>Tryptase increased L6 myoblast proliferation by 35% above control group and this effect was completely inhibited by APC-366. We confirmed the expression of PAR-2 receptor <it>in vivo </it>in skeletal muscle cells and in satellite cells and <it>in vitro </it>in L6 cells, where PAR-2 was found to be functional. Trypsin and SLIGKV increased L6 cells proliferation by 76% and 26% above control, respectively. COX-2 activity was increased following stimulation with PAR-2 agonist but its expression remained unchanged. Inhibition of COX-2 activity by NS-398 abolished the stimulation of cell proliferation induced by tryptase and trypsin. Finally, 15-deoxy-Δ-^12,14-prostaglandin J₂(15Δ-PGJ₂), a product of COX-2-derived prostaglandin D₂, stimulated myoblast proliferation, but not PGE₂and PGF₂α.</p> <p>Conclusions</p> <p>Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2.</p

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P &lt; 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P &lt; 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P &lt; 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P &lt; 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P &lt; 0.001; OR(BP) = 2.4, P &lt; 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P &lt; 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P &lt; 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Étude par spectrométrie infrarouge et raman du formyl-2-pyrrole

Les spectres infrarouges et Banian du formyl-2-pyrrole, C4H3NHCHO, et de ses dérivés deutériés, C4H3NDCHO, C4H3NHCDO et C4H3NDCDO liquides et cristallisés ont été enregistrés entre 4 000 et 40 cm-1. Les spectres infrarouges du gaz et de solutions ont aussi été examinés. Sur les 30 vibrations fondamentales attendues, 23 à l’étal gazeux et 30 dans les étals condensés sont attribuées en termes de vibrations de groupes. Les fréquences observées sont comparées à celles du pyrrole et d'autres aldéhydes. La conformation de la molécule, la barrière de torsion du groupement CHO et l’influence de ce groupement sur les propriétés moléculaires sont discutées. Les molécules sont associées par des liaisons hydrogène NH ... O en dimères fermés à l’état liquide et en chaînes infinies dans le cristal. Cette liaison hydrogène est relativement forte à cause de l’augmentation de l’acidité du groupement NH et de la plus grande basicité de l’oxygène aldéhydique ; elle est caractérisée, dans le cristal, par un déplacement relatif de la vibration νNH voisin de 10 % et par une distance N ... O d’environ 2,90 Å

Evaluation de l'huile de chaîne à base végétale

peer reviewe

Measurement of linear and nonlinear loudspeaker parameters using high speed cameras and 3D vision methods

International audienc

Role of ley pastures in tomorrow’s cropping systems. A review

International audienceAbstractDiversification of cropping systems has been proposed as a major mechanism to move towards sustainable cropping systems. To date, a diversification option that has received little attention is introduction of ley pastures into cropping systems, but the use of ley pastures is challenged by most future-oriented scenarios aiming to feed the world sustainably. In these scenarios, ruminant livestock feed only on permanent pastures, while cropping systems focus completely on production of crop-based human food. Diversification of cropping systems with ley pastures is thus compromised by knowledge gaps and future-oriented policy options. Here, we review ecosystem services provided by introducing ley pastures into cropping systems to increase sustainability of agriculture, discuss types of ley pastures and their management liable to promote these services, and raise future challenges related to introducing ley pastures into cropping systems. We conclude that (1) ley pastures provide a large set of input (soil conservation, nutrient provision and recycling, soil water retention, biological control of pests) and output (water purification, climate regulation, habitat provision for biodiversity conservation, forage production) ecosystem services of primary importance to cropping systems and society, respectively, as long as their spatial and temporal insertion within cropping systems is well-managed; otherwise, disservices may be produced. (2) To benefit from ecosystem services provided by ley pastures in cropping systems while limiting their disservices, it appears necessary to define a safe operating space for ley pastures in cropping systems. Moving towards this space requires changing plant breeding programs towards multiservice ley pastures, producing knowledge about emerging ways of introducing ley pastures into cropping systems (e.g., living mulch, green manure) and better quantifying the bundles of ecosystem services provided by ley pastures in cropping systems

Key research challenges to supporting farm transitions to agroecology in advanced economies. A review

International audienceIn response to the sustainability issues that agriculture faces in advanced economies, agroecology has gained increasing relevance in scientific, political, and social debates. This has promoted discussion about transitions to agroecology, which represents a significant advancement. Accordingly, it has become a growing field of research. We reviewed the literature on and in support of farm transitions to agroecology in advanced economies in order to identify key research challenges and suggest innovative research paths. Our findings can be summarized as follows: (1) Research that supports exploration and definition of desired futures, whether based on future-oriented modeling or expert-based foresight approaches, should more explicitly include the farm level. It should stimulate the creativity and design ability of farmers and other stakeholders, and also address issues of representation and power among them. (2) Research that creates awareness and assesses farms before, during or after transition requires more holistic and dynamic assessment frameworks. These frameworks need to be more flexible to adapt to the diversity of global and local challenges. Their assessment should explicitly include uncertainty due to the feedback loops and emergent properties of transitions. (3) Research that analyzes and supports farms during transition should focus more on the dynamics of change processes by valuing what happens on the farms. Research should especially give more credence to on-farm experiments conducted by farmers and develop new tools and methods (e.g., for strategic monitoring) to support these transitions. This is the first review of scientific studies of farm transitions to agroecology. Overall, the review indicates that these transitions challenge the system boundaries, temporal horizons, and sustainability dimensions that agricultural researchers usually consider. In this context, farm transitions to agroecology require changes in the current organization and funding of research in order to encourage longer term and more adaptive configurations. Keywords Transformation • Sustainable agriculture • Farm • Coupled innovations • Assessment • Design • Foresight Contents Lorène Prost and Guillaume Martin contributed equally

Key research challenges to supporting farm transitions to agroecology in advanced economies. A review

International audienceIn response to the sustainability issues that agriculture faces in advanced economies, agroecology has gained increasing relevance in scientific, political, and social debates. This has promoted discussion about transitions to agroecology, which represents a significant advancement. Accordingly, it has become a growing field of research. We reviewed the literature on and in support of farm transitions to agroecology in advanced economies in order to identify key research challenges and suggest innovative research paths. Our findings can be summarized as follows: (1) Research that supports exploration and definition of desired futures, whether based on future-oriented modeling or expert-based foresight approaches, should more explicitly include the farm level. It should stimulate the creativity and design ability of farmers and other stakeholders, and also address issues of representation and power among them. (2) Research that creates awareness and assesses farms before, during or after transition requires more holistic and dynamic assessment frameworks. These frameworks need to be more flexible to adapt to the diversity of global and local challenges. Their assessment should explicitly include uncertainty due to the feedback loops and emergent properties of transitions. (3) Research that analyzes and supports farms during transition should focus more on the dynamics of change processes by valuing what happens on the farms. Research should especially give more credence to on-farm experiments conducted by farmers and develop new tools and methods (e.g., for strategic monitoring) to support these transitions. This is the first review of scientific studies of farm transitions to agroecology. Overall, the review indicates that these transitions challenge the system boundaries, temporal horizons, and sustainability dimensions that agricultural researchers usually consider. In this context, farm transitions to agroecology require changes in the current organization and funding of research in order to encourage longer term and more adaptive configurations. Keywords Transformation • Sustainable agriculture • Farm • Coupled innovations • Assessment • Design • Foresight Contents Lorène Prost and Guillaume Martin contributed equally