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Abstract Background DNA microarray technology has had a great impact on muscle research and microarray gene expression data has been widely used to identify gene signatures characteristic of the studied conditions. With the rapid accumulation of muscle microarray data, it is of great interest to understand how to compare and combine data across multiple studies. Meta-analysis of transcriptome data is a valuable method to achieve it. It enables to highlight conserved gene signatures between multiple independent studies. However, using it is made difficult by the diversity of the available data: different microarray platforms, different gene nomenclature, different species studied, etc. Description We have developed a system tool dedicated to muscle transcriptome data. This system comprises a collection of microarray data as well as a query tool. This latter allows the user to extract similar clusters of co-expressed genes from the database, using an input gene list. Common and relevant gene signatures can thus be searched more easily. The dedicated database consists in a large compendium of public data (more than 500 data sets) related to muscle (skeletal and heart). These studies included seven different animal species from invertebrates (Drosophila melanogaster, Caenorhabditis elegans) and vertebrates (Homo sapiens, Mus musculus, Rattus norvegicus, Canis familiaris, Gallus gallus). After a renormalization step, clusters of co-expressed genes were identified in each dataset. The lists of co-expressed genes were annotated using a unified re-annotation procedure. These gene lists were compared to find significant overlaps between studies. Conclusions Applied to this large compendium of data sets, meta-analyses demonstrated that conserved patterns between species could be identified. Focusing on a specific pathology (Duchenne Muscular Dystrophy) we validated results across independent studies and revealed robust biomarkers and new pathways of interest. The meta-analyses performed with MADMuscle show the usefulness of this approach. Our method can be applied to all public transcriptome data.

Aims Mutations in the KCNK3 gene, which encodes for an outward-rectifier K+ channel, have been identified in patients suffering from pulmonary arterial hypertension (PAH), and constitute the first described channelopathy in PAH. In human PAH and experimental pulmonary hypertension (PH), we demonstrated that KCNK3 expression and function are severely reduced in pulmonary vascular cells, promoting PH-like phenotype at the morphologic and haemodynamic levels. Since KCNK3 channel is also expressed in both the human and rodent heart, we aimed to elucidate the pathophysiological role of KCNK3 channel in right ventricular (RV) hypertrophy (RVH) related to PH. Methods and results Using whole-cell Patch-clamp technique, we demonstrated that KCNK3 is predominantly expressed in adult rat RV cardiomyocytes compared to the left ventricle cardiomyocytes and participates in the repolarizing phase of the RV action potential. We revealed a reduction in KCNK3 function prior to development of RVH and the rise of pulmonary vascular resistance. KCNK3 function is severely reduced in RV cardiomyocytes during the development of RVH in several rat models of PH (exposure to monocrotaline, chronic hypoxia, and Sugen/hypoxia) and chronic RV pressure overload (pulmonary artery banding). In experimental PH, we revealed a reduction in KCNK3 function before any rise in pulmonary vascular resistance and the development of RVH. KCNK3 mRNA level is also reduced in human RV tissues from PAH patients compared to non-PAH patients. In line with these findings, chronic inhibition of KCNK3 in rats with the specific inhibitor (A293) induces RV hypertrophy which is associated with the reexpression of foetal genes, RV fibrosis, RV inflammation, and subsequent loss of RV performance as assessed by echocardiography. Conclusion Our data indicate that loss of KCNK3 function and expression is a hallmark of the RV hypertrophy/dysfunction associated with PH. [ABSTRACT FROM AUTHOR]

Heart failure is still a major cause of hospitalization and mortality in developed countries. Many clinical trials have tested the use of multipotent stem cells as a cardiac regenerative medicine. The benefit for the patients of this therapeutic intervention has remained limited. Herein, we review the pluripotent stem cells as a cell source for cardiac regeneration. We more specifically address the various challenges of this cell therapy approach. We question the cell delivery systems, the immune tolerance of allogenic cells, the potential proarrhythmic effects, various drug mediated interventions to facilitate cell grafting and, finally, we describe the pathological conditions that may benefit from such an innovative approach. As members of a transatlantic consortium of excellence of basic science researchers and clinicians, we propose some guidelines to be applied to cell types and modes of delivery in order to translate pluripotent stem cell cardiac derivatives into safe and effective clinical trials. S tem C ells 2016;34:34-43 [ABSTRACT FROM AUTHOR]

Money was, until Keynes and Friedman, the great absence in economic literature. After them, relations between money and long economic cycles have been in their turn absent in debate. Perhaps this conform an explanation for logical and chronological relations between business cycles and long cycles been scarcely explored. Notwithstanding, is in those three directions where a new monetary theory should be researched for. This ought to be a more dynamic one. Thus, we can propose as economic models Porter's diamond, applied to money, and Monet value Chain. The aim is to reflect on a "social dimension for money" announcing than of monetary policy, and evoking meanwhile the rhythms followed by that perception and the means for managing it, along the long cycle. Still, it would mean bringing together macro economic model and strategic model, in a second step, in order to practically be more able to forecast and prevent conflicts, accumulate human capital, and allow a social project to emerge behind that sort of new long monetary cycle. [ABSTRACT FROM AUTHOR]

Bone remodeling involves synthesis of organic matrix by osteoblasts and bone resorption by osteoclasts. A tight collaboration between these two cell types is essential to maintain a physiological bone homeostasis. Thus, osteoblasts control bone-resorbing activities and are also involved in osteoclast differentiation. Any disturbance between these effectors leads to the development of skeletal abnormalities and/or bone diseases. In this context, the determination of key genes involved in bone cell differentiation is a new challenge to treat any skeletal disorders. Different models are used to study the differentiation process of these cells, but all of them use pre-engaged progenitor cells, allowing us to study only the latest stages of the differentiation. Embryonic stem (ES) cells come from the inner mass of the blastocyst prior its implantation to the uterine wall. Because of their capacity to differentiate into all germ layers, and so into all tissues of the body, ES cells represent the best model by which to study earliest stages of bone cell differentiation. Osteoblasts are generated by two methods, one including the generation of embryoid body, the other not. Mineralizing cells are obtained after 2 weeks of culture and express all the specific osteoblastic markers (alkaline phosphatase, type I collagen, osteocalcin, and others). Osteoclasts are generated from a single-cell suspension of ES cells seeded on a feeder monolayer, and bone-resorbing cells expressing osteoclastic markers such as tartrate-resistant alkaline phosphatase or receptor activator of nuclear factor κB are obtained within 11 days. The aim of this review is to present recent discoveries and advances in the differentiation of both osteoblasts and osteoclasts from ES cells. [ABSTRACT FROM AUTHOR]

Objective: We examined the functional consequences of expressing adult rabbit fast skeletal sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA1a) in isolated adult rat ventricular myocytes. Methods: Myocytes were infected with a recombinant adenovirus harboring SERCA1a. Then 2 days after myocyte infection, protein expression was estimated using Western blot and SDS–PAGE analysis. We also measured the ATP-dependent oxalate-facilitated Ca2+ uptake of myocyte homogenates and monitored Ca2+ transient in myocytes loaded with the Ca2+ dye, indo-1. Results: SERCA1a gene expression resulted in a 36% increase in the total SERCA protein level in infected myocytes compared to controls (P<0.01), while SERCA2 and phospholamban levels did not change. This increase was associated with a 42% rise in SR Ca2+ uptake (P<0.01), while τ (the time constant of Ca2+ transient decay), and the time to peak fell by 32% (P<0.01) and 38% (P<0.001), respectively. Increasing the frequency of stimulation from 0.2 to 2 Hz decreased τ in both cell types (P<0.01). However, the decrease was much smaller in infected (P<0.01) than in uninfected cells (P<0.001). Isoproterenol (1 μM) further decreased τ in infected myocytes by 23% (P<0.05). In these cells, the diastolic [Ca2+]i decreased by 50% (P<0.05) while the systolic [Ca2+]i increased by 19% (P<0.05). No difference was found in the speed of SR Ca2+ reloading after caffeine washout between the two cell types. Conclusion: Adenovirus-mediated SERCA1a gene transfer to adult rat ventricular myocytes enhances SR Ca2+ handling to a degree similar to that observed following physiological stimulation. [ABSTRACT FROM PUBLISHER]