144 research outputs found
Le concept album : une vaste « escrockerie » ?
Exercice de style largement galvaudé de nos jours, le « concept album » est un genre qui a vu le jour dans la deuxième partie des années 1960. À cet égard, il est l’un des stigmates des orientations artistiques qui animaient la scène Pop d’alors, frappée du sceau de la « révolution psychédélique ». Le Rock’n’roll des fifties y a connu de fortes mutations, sous l’influence principale des Beatles, puisant dans d’autres formes d’expression, notamment les musiques « savantes ». En 1969, les Who transposent l’Opéra dans le monde de la Pop : leur album « Tommy », notoirement connu pour être le premier Opéra rock de l’histoire, inaugure une longue série de concept albums. L’idée étant de concevoir le LP non plus comme une simple compilation de titres indépendants, mais comme un tout où les chansons servent de support à une histoire. Cette idée, qui fut abondamment reprise, n’a pas manqué de susciter des réserves, voire la moquerie de certains observateurs. Selon eux, l’album concept est l’une des illustrations des « dérives progressives » qui vont se confirmer dans les années 1970. En ce sens que le « vrai rock’n’roll » se serait perdu dans sa recherche de crédibilité artistique. Mais au-delà de ces considérations esthétiques, l’étude du concept album, en tant que véhicule d’une narration, soulève la question de la place des textes dans la musique Pop ou Rock
In-Silico Patterning of Vascular Mesenchymal Cells in Three Dimensions
Cells organize in complex three-dimensional patterns by interacting with proteins along with the surrounding extracellular matrix. This organization provides the mechanical and chemical cues that ultimately influence a cell's differentiation and function. Here, we computationally investigate the pattern formation process of vascular mesenchymal cells arising from their interaction with Bone Morphogenic Protein-2 (BMP-2) and its inhibitor, Matrix Gla Protein (MGP). Using a first-principles approach, we derive a reaction-diffusion model based on the biochemical interactions of BMP-2, MGP and cells. Simulations of the model exhibit a wide variety of three-dimensional patterns not observed in a two-dimensional analysis. We demonstrate the emergence of three types of patterns: spheres, tubes, and sheets, and show that the patterns can be tuned by modifying parameters in the model such as the degradation rates of proteins and chemotactic coefficient of cells. Our model may be useful for improved engineering of three-dimensional tissue structures as well as for understanding three dimensional microenvironments in developmental processes.National Institutes of Health (U.S.) (GM69811)United States. Dept. of Energy (DOE CSGF fellowship
Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner
WOS: 000300421300010PubMed ID: 21750166Vascular calcification (VC), mainly due to elevated phosphate levels, is one major problem in patients suffering from chronic kidney disease. In clinical studies, an inverse relationship between serum magnesium and VC has been reported. However, there is only few information about the influence of magnesium on calcification on a cellular level available. Therefore, we investigated the effect of magnesium on calcification induced by beta-glycerophosphate (BGP) in bovine vascular smooth muscle cells (BVSMCs). BVSMCs were incubated with calcification media for 14 days while simultaneously increasing the magnesium concentration. Calcium deposition, transdifferentiation of cells and apoptosis were measured applying quantification of calcium, von Kossa and Alizarin red staining, real-time reverse transcription-polymerase chain reaction and annexin V staining, respectively. Calcium deposition in the cells dramatically increased with addition of BGP and could be mostly prevented by co-incubation with magnesium. Higher magnesium levels led to inhibition of BGP-induced alkaline phosphatase activity as well as to a decreased expression of genes associated with the process of transdifferentiation of BVSMCs into osteoblast-like cells. Furthermore, estimated calcium entry into the cells decreased with increasing magnesium concentrations in the media. In addition, higher magnesium concentrations prevented cell damage (apoptosis) induced by BGP as well as progression of already established calcification. Higher magnesium levels prevented BVSMC calcification, inhibited expression of osteogenic proteins, apoptosis and further progression of already established calcification. Thus, magnesium is influencing molecular processes associated with VC and may have the potential to play a role for VC also in clinical situations.Fresenius Medical Care Deutschland GmbH, GermanyThis study was supported by Fresenius Medical Care Deutschland GmbH, Germany
Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair
Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebrae, which form in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments
Neoantigen quality predicts immunoediting in survivors of pancreatic cancer.
Cancer immunoediting1 is a hallmark of cancer2 that predicts that lymphocytes kill more immunogenic cancer cells to cause less immunogenic clones to dominate a population. Although proven in mice1,3, whether immunoediting occurs naturally in human cancers remains unclear. Here, to address this, we investigate how 70 human pancreatic cancers evolved over 10 years. We find that, despite having more time to accumulate mutations, rare long-term survivors of pancreatic cancer who have stronger T cell activity in primary tumours develop genetically less heterogeneous recurrent tumours with fewer immunogenic mutations (neoantigens). To quantify whether immunoediting underlies these observations, we infer that a neoantigen is immunogenic (high-quality) by two features-'non-selfness' based on neoantigen similarity to known antigens4,5, and 'selfness' based on the antigenic distance required for a neoantigen to differentially bind to the MHC or activate a T cell compared with its wild-type peptide. Using these features, we estimate cancer clone fitness as the aggregate cost of T cells recognizing high-quality neoantigens offset by gains from oncogenic mutations. With this model, we predict the clonal evolution of tumours to reveal that long-term survivors of pancreatic cancer develop recurrent tumours with fewer high-quality neoantigens. Thus, we submit evidence that that the human immune system naturally edits neoantigens. Furthermore, we present a model to predict how immune pressure induces cancer cell populations to evolve over time. More broadly, our results argue that the immune system fundamentally surveils host genetic changes to suppress cancer
Analysis of mass spectrometry data from the secretome of an explant model of articular cartilage exposed to pro-inflammatory and anti-inflammatory stimuli using machine learning
Background: Osteoarthritis (OA) is an inflammatory disease of synovial joints involving the loss and degeneration of articular cartilage. The gold standard for evaluating cartilage loss in OA is the measurement of joint space width on standard radiographs. However, in most cases the diagnosis is made well after the onset of the disease, when the symptoms are well established. Identification of early biomarkers of OA can facilitate earlier diagnosis, improve disease monitoring and predict responses to therapeutic interventions.
Methods: This study describes the bioinformatic analysis of data generated from high throughput proteomics for identification of potential biomarkers of OA. The mass spectrometry data was generated using a canine explant model of articular cartilage treated with the pro-inflammatory cytokine interleukin 1 β (IL-1β). The bioinformatics analysis involved the application of machine learning and network analysis to the proteomic mass spectrometry data. A rule based machine learning technique, BioHEL, was used to create a model that classified the samples into their relevant treatment groups by identifying those proteins that separated samples into their respective groups. The proteins identified were considered to be potential biomarkers. Protein networks were also generated; from these networks, proteins pivotal to the classification were identified.
Results: BioHEL correctly classified eighteen out of twenty-three samples, giving a classification accuracy of 78.3% for the dataset. The dataset included the four classes of control, IL-1β, carprofen, and IL-1β and carprofen together. This exceeded the other machine learners that were used for a comparison, on the same dataset, with the exception of another rule-based method, JRip, which performed equally well. The proteins that were most frequently used in rules generated by BioHEL were found to include a number of relevant proteins including matrix metalloproteinase 3, interleukin 8 and matrix gla protein.
Conclusions: Using this protocol, combining an in vitro model of OA with bioinformatics analysis, a number of relevant extracellular matrix proteins were identified, thereby supporting the application of these bioinformatics tools for analysis of proteomic data from in vitro models of cartilage degradation
Overexpression of Akt1 Enhances Adipogenesis and Leads to Lipoma Formation in Zebrafish
<div><h3>Background</h3><p>Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the <em>Akt1</em> gene.</p> <h3>Methodology/Principal Findings</h3><p><em>Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1</em>)<sup>cy18</sup> displays severely obese phenotypes at the adult stage. In Tg(<em>krt4:Hsa.myrAkt1</em>)<sup>cy18</sup>, the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3α/β, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(<em>krt4:Hsa.myrAkt1</em>)<sup>cy18</sup> caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(<em>krt4:Hsa.myrAkt1</em>)<sup>cy18</sup>. In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(<em>krt4:Hsa.myrAkt1</em>)<sup>cy18</sup>, suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues.</p> <h3>Conclusion/Significance</h3><p>Collectively, the findings of this study provide direct evidence that Akt1 signaling plays an important role in balancing normal levels of fat tissue in vivo. The obese zebrafish examined in this study could be a new powerful model to screen novel drugs for the treatment of human obesity.</p> </div
Les algues dulcaquicoles des Vosges et les pluies acides
CNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc
Analysis of positive corona in wire-to-plate electrostatic precipitator
This paper analyses corona discharge in ambient air flow associated with laboratory-scaled wire-to-plate electrostatic precipitator (WPESP). The corona discharge is analysed by a combined iterative computational technique based on the finite element method (FEM) and charge simulation method (CSM). The phenomenon is mathematically described by Maxwell's equations in differential form. A finite element method is used to solve the Poisson's equation and the charge simulation method is used to satisfy the current continuity condition. Measurement method of the positive dc corona current density and electric field, taking into account the air flow velocity, has been introduced. The computed results are compared with experimental results to test the effectiveness of this approach
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