Durabilité des sols et systèmes de récolte : le rôle clé des acteurs. Compte rendu de l’atelier 2

L’atelier 2 Durabilité des sols et systèmes de récolte : le rôle clé des acteurs a rassemblé dix-huit personnes qui ont exploré la façon dont la durabilité des sols forestiers est prise en compte par les acteurs de la filière forêtbois, et comment cette durabilité des sols pourrait mieux l’être lors de la récolte et du reboisement. Trois retours d’expérience ont aussi été présentés. Des solutions techniques et organisationnelles ont prouvé leur efficacité, d’autres essais ont connu des échecs. Les voies de progrès concernent : les techniques de chantiers ; la sensibilisation, l’organisation et la formation des acteurs ; la prise en charge des coûts directs et indirects

HI intensity mapping with FAST

We discuss the detectability of large-scale HI intensity fluctuations using the FAST telescope. We present forecasts for the accuracy of measuring the Baryonic Acoustic Oscillations and constraining the properties of dark energy. The FAST $19$-beam L-band receivers ($1.05$--$1.45$ GHz) can provide constraints on the matter power spectrum and dark energy equation of state parameters ($w_{0},w_{a}$) that are comparable to the BINGO and CHIME experiments. For one year of integration time we find that the optimal survey area is $6000\,{\rm deg}^2$. However, observing with larger frequency coverage at higher redshift ($0.95$--$1.35$ GHz) improves the projected errorbars on the HI power spectrum by more than $2~\sigma$ confidence level. The combined constraints from FAST, CHIME, BINGO and Planck CMB observations can provide reliable, stringent constraints on the dark energy equation of state.Comment: 7 pages, 3 figures, submitted to "Frontiers in Radio Astronomy and FAST Early Sciences Symposium 2015" conference proceedin

Skeletal muscle characteristics are preserved in hTERT/cdk4 human myogenic cell lines

Background: hTERT/cdk4 immortalized myogenic human cell lines represent an important tool for skeletal muscle research, being used as therapeutically pertinent models of various neuromuscular disorders and in numerous fundamental studies of muscle cell function. However, the cell cycle is linked to other cellular processes such as integrin regulation, the PI3K/Akt pathway, and microtubule stability, raising the question as to whether genetic modification related to the cell cycle results in secondary effects that could undermine the validity of these cell models.Results: Here we subjected five healthy and disease muscle cell isolates to transcriptomic analysis, comparing immortalized lines with their parent primary populations in both differentiated and undifferentiated states, and testing their myogenic character by comparison with non-myogenic (CD56-negative) cells. Principal component analysis of global gene expression showed tight clustering of immortalized myoblasts to their parent primary populations, with clean separation from the non-myogenic reference. Comparison was made to publicly available transcriptomic data from studies of muscle human pathology, cell, and animal models, including to derive a consensus set of genes previously shown to have altered regulation during myoblast differentiation. Hierarchical clustering of samples based on gene expression of this consensus set showed that immortalized lines retained the myogenic expression patterns of their parent primary populations. Of 2784 canonical pathways and gene ontology terms tested by gene set enrichment analysis, none were significantly enriched in immortalized compared to primary cell populations. We observed, at the whole transcriptome level, a strong signature of cell cycle shutdown associated with senescence in one primary myoblast population, whereas its immortalized clone was protected.Conclusions: Immortalization had no observed effect on the myogenic cascade or on any other cellular processes, and it was protective against the systems level effects of senescence that are observed at higher division counts of primary cells

0087: Sleep apneas treatment during cardiac rehabilitation can improve heart failure prognosis? SATELIT-HF study: sleep apnea treatment during cardiac rehabilitation of CHF patients

BackgroundSleep-disordered breathing (SDB) is commonly in chronic heart failure (CHF) patients.Exercise training (ET) improves exercise tolerance and reduces cardiac decompensations in CHF population. Otherwise, ventilation therapy (VT) improves prognosis and exercise capacity in CHF patients with SDB. However, the effect of the combination therapy: ET and VT is still unexplored. The aim of our study is to evaluate the effects on hemodynamic status (cardiac decompensations) of ET and VT in stable CHF patients referred to cardiac rehabilitation (CR).MethodsWe included 118 stable CHF patients with an apnea-hypopnea index (AHI)>15/h diagnosed by polygraphy. They were randomized into exercise training (ET group n=58) or combined exercise and ventilation (ET+VT group n=60). The follow up period was the 8 weeks during which 20 exercise training sessions were scheduled. Severe episodes of cardiac decompensations were recorded.ResultsThe mean age was 62.6±10.3 years, 89% were males, 50% NYHA class II and 50% in class III, mean LVEF was 30%. 40% and 60% of patients had respectively obstructive and central and/or mixed apneas, with a mean AHI 34.4±14.3/h. Patients of ET+VT group had significantly fewer acute cardiovascular events than those of ET group (2/60 vs. 7/58; 3.3% vs. 15.5%, p<0.05).ConclusionVentilation therapy combined with ET in severe CHF patients seems to reinforce benefits of ET alone. Screening of SDB in CR could be proposed in order to optimize the global management of the heart disease

Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells

Caveolin-3 is the major structural protein of caveolae in muscle. Mutations in the CAV3 gene cause different types of myopathies with altered membrane integrity and repair, expression of muscle proteins, and regulation of signaling pathways. We show here that myotubes from patients bearing the CAV3P28L and R26Q mutations present a dramatic decrease of caveolae at the plasma membrane, resulting in abnormal response to mechanical stress. Mutant myotubes are unable to buffer the increase in membrane tension induced by mechanical stress. This results in impaired regulation of the IL6/STAT3 signaling pathway leading to its constitutive hyperactivation and increased expression of muscle genes. These defects are fully reversed by reassembling functional caveolae through expression ofcaveolin-3. Our study reveals that under mechanical stress the regulation of mechan-oprotection by caveolae is directly coupled with the regulation of IL6/STAT3 signaling inmuscle cells and that this regulation is absent in Cav3-associated dystrophic patients

A transcriptome multi-tissue analysis identifies biological pathways and genes associated with variations in feed efficiency of growing pigs

International audienceBackground - Animal's efficiency in converting feed into lean gain is a critical issue for the profitability of meat industries. This study aimed to describe shared and specific molecular responses in different tissues of pigs divergently selected over eight generations for residual feed intake (RFI). Results - Pigs from the low RFI line had an improved gain-to-feed ratio during the test period and displayed higher leanness but similar adiposity when compared with pigs from the high RFI line at 132 days of age. Transcriptomics data were generated from longissimus muscle, liver and two adipose tissues using a porcine microarray and analyzed for the line effect (n = 24 pigs per line). The most apparent effect of the line was seen in muscle, whereas subcutaneous adipose tissue was the less affected tissue. Molecular data were analyzed by bioinformatics and subjected to multidimensional statistics to identify common biological processes across tissues and key genes participating to differences in the genetics of feed efficiency. Immune response, response to oxidative stress and protein metabolism were the main biological pathways shared by the four tissues that distinguished pigs from the low or high RFI lines. Many immune genes were under-expressed in the four tissues of the most efficient pigs. The main genes contributing to difference between pigs from the low vs high RFI lines were CD40, CTSC and NTN1. Different genes associated with energy use were modulated in a tissue-specific manner between the two lines. The gene expression program related to glycogen utilization was specifically up-regulated in muscle of pigs from the low RFI line (more efficient). Genes involved in fatty acid oxidation were down-regulated in muscle but were promoted in adipose tissues of the same pigs when compared with pigs from the high RFI line (less efficient). This underlined opposite line-associated strategies for energy use in skeletal muscle and adipose tissue. Genes related to cholesterol synthesis and efflux in liver and perirenal fat were also differentially regulated in pigs from the low vs high RFI lines. Conclusions - Non-productive functions such as immunity, defense against pathogens and oxidative stress contribute likely to inter-individual variations in feed efficiency

Regenerative potential of human muscle stem cells in chronic inflammation

International audienceABSTRACT: INTRODUCTION: Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle. METHODS: As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation. RESULTS: After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group. CONCLUSIONS: In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate

Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders

<p>Abstract</p> <p>Background</p> <p>Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Isolation of reliable and stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with muscle aging, and for developing innovative gene-based, cell-based or pharmacological biotherapies.</p> <p>Methods</p> <p>Using transduction with both telomerase-expressing and cyclin-dependent kinase 4-expressing vectors, we were able to generate a battery of immortalized human muscle stem-cell lines from patients with various neuromuscular disorders.</p> <p>Results</p> <p>The immortalized human cell lines from patients with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2B had greatly increased proliferative capacity, and maintained their potential to differentiate both <it>in vitro </it>and <it>in vivo </it>after transplantation into regenerating muscle of immunodeficient mice.</p> <p>Conclusions</p> <p>Dystrophic cellular models are required as a supplement to animal models to assess cellular mechanisms, such as signaling defects, or to perform high-throughput screening for therapeutic molecules. These investigations have been conducted for many years on cells derived from animals, and would greatly benefit from having human cell models with prolonged proliferative capacity. Furthermore, the possibility to assess <it>in vivo </it>the regenerative capacity of these cells extends their potential use. The innovative cellular tools derived from several different neuromuscular diseases as described in this report will allow investigation of the pathophysiology of these disorders and assessment of new therapeutic strategies.</p

A functional human motor unit platform engineered from human embryonic stem cells and immortalized skeletal myoblasts.

Although considerable research on neuromuscular junctions (NMJs) has been conducted, the prospect of in vivo NMJ studies is limited and these studies are challenging to implement. Therefore, there is a clear unmet need to develop a feasible, robust, and physiologically relevant in vitro NMJ model. We aimed to establish a novel functional human NMJs platform, which is serum and neural complex media/neural growth factor-free, using human immortalized myoblasts and human embryonic stem cells (hESCs)-derived neural progenitor cells (NPCs) that can be used to understand the mechanisms of NMJ development and degeneration. Immortalized human myoblasts were co-cultured with hESCs derived committed NPCs. Over the course of the 7 days myoblasts differentiated into myotubes and NPCs differentiated into motor neurons. Neuronal axon sprouting branched to form multiple NMJ innervation sites along the myotubes and the myotubes showed extensive, spontaneous contractile activity. Choline acetyltransferase and βIII-tubulin immunostaining confirmed that the NPCs had matured into cholinergic motor neurons. Postsynaptic site of NMJs was further characterized by staining dihydropyridine receptors, ryanodine receptors, and acetylcholine receptors by α-bungarotoxin. We established a functional human motor unit platform for in vitro investigations. Thus, this co-culture system can be used as a novel platform for 1) drug discovery in the treatment of neuromuscular disorders, 2) deciphering vital features of NMJ formation, regulation, maintenance, and repair, and 3) exploring neuromuscular diseases, age-associated degeneration of the NMJ, muscle aging, and diabetic neuropathy and myopathy