Metabolic Syndrome: The Danger Signal in Atherosclerosis

Atherosclerosis is a chronic inflammatory disease characterized by infiltration of blood vessels by lipids and leukocytes. There is a growing body of evidence that among risk factors that promote atherosclerosis, the metabolic syndrome is a powerful and prevalent predictor of cardiovascular events. The systemic inflammatory process associated with the metabolic syndrome has numerous deleterious effects that promote plaque activation, which is responsible for clinical events. Interactions between the innate immune system with lipid-derived products seem to play a major role in the pathophysiology of atherosclerosis in relation with the metabolic syndrome. The multiple links among adipose tissue, the vascular wall, and the immune system are the topics of this review, which examines the roles of oxidized low-density lipoprotein, inflammatory cytokines, and adipokines in triggering and perpetuating a danger signal response that promotes the development of atherosclerosis. Furthermore, therapeutic options that specifically target the metabolic syndrome components are reviewed in light of recent developments

Processus d'apprentissage et de création des improvisateurs experts en musique classique

Contrairement à l’idée reçue selon laquelle la capacité à improviser serait innée, la recherche a démontré qu’elle peut être améliorée par un entraînement délibéré (Brophy, 2001; Kenny et Gellrich, 2002; Kratus, 1991, 1995). Par ailleurs, l’apprentissage et la pratique de l’improvisation exerceraient un effet positif sur l’acquisition et le développement de plusieurs autres compétences, aussi bien musicales que non musicales (Azzara, 1993; Campbell, 2009; Dos Santos et Del Ben, 2004; Kenny et Gellrich, 2002; Koutsoupidou et Hargreaves, 2009; McPherson, 1993; Wilson, 1970). Cependant, l’état actuel des connaissances ne permet pas d’outiller efficacement le pédagogue souhaitant intégrer l’improvisation à la démarche d’apprentissage du musicien classique de niveau collégial ou universitaire (Després, 2011; Després et Dubé, 2015; Dubé et Després, 2012). Par ce projet doctoral, je souhaite contribuer à combler cette lacune en mettant en lumière trois dimensions de l’expertise en improvisation musicale classique : l’acquisition des compétences, la production de l’improvisation et la transmission des savoirs, savoir-faire et savoir-être. Afin de documenter le parcours d’apprentissage, les stratégies de performances ainsi que les approches d’enseignement-apprentissage des instrumentistes et pédagogues experts en improvisation musicale classique, un devis méthodologique en trois phases a été élaboré. La première phase visait à répondre à la question de recherche suivante : « Qu’est-ce qui caractérise le parcours d’apprentissage des improvisateurs experts en musique classique? ». Afin de répondre à cette question, des entrevues ont été réalisées auprès de N = 8 improvisateurs classiques experts de la scène internationale au sujet de leur parcours d’apprentissage de l’improvisation. Ensuite, la deuxième phase visait à répondre à la question de recherche suivante : « Quelles stratégies sont mises en œuvre par les improvisateurs experts en musique classique lors de leurs prestations? ». Une méthode novatrice, reposant sur la stratégie de collecte de données du protocole verbal rétrospectif avec aide à la remémoration subjective, a été mise en place afin de répondre à cette question. N = 5 improvisateurs classiques experts de la scène nationale ont participé à cette phase. La troisième phase de la recherche visait à répondre à la question suivante : « Quels éléments liés à l’expérience, aux représentations, au parcours d’apprentissage ou à la pratique pédagogique des experts du domaine pourraient contribuer à bonifier l’enseignement-apprentissage de l’improvisation musicale classique? ». Au total, N = 15 participants ont été interviewés lors de cette phase. Parmi ces 15 participants, quatre ont été identifiés comme étant experts en improvisation musicale classique, deux comme enseignants experts en improvisation musicale classique et, ces deux dernières catégories n’étant pas exclusives, neuf comme appartenant à la fois à ces deux catégories. Les trois phases de ce projet doctoral ont contribué à enrichir les connaissances au sujet de l’enseignement-apprentissage et de la production de l’improvisation musicale dans le contexte classique, posant ainsi les fondements empiriques d’une pédagogie efficiente de l’improvisation.Contrary to the widespread belief that the ability to improvise in music is innate, research has shown that it can be enhanced through deliberate training (Brophy, 2001; Kenny & Gellrich 2002; Kratus, 1991, 1995). Furthermore, the learning and practice of improvisation positively influences the acquisition and development of several other musical and non-musical skills (Azzara, 1993; Campbell, 2009; Dos Santos & Del Ben, 2004; Kenny & Gellrich 2002; Koutsoupidou & Hargreaves, 2009; McPherson, 1993; Wilson, 1970). However, the actual state of knowledge is not sufficient to empower the pedagogue wishing to integrate improvisation throughout the learning process of the classical musician at the college or the university level (Després, 2011; Després & Dubé, 2015; Dubé & Després, 2012). This doctoral thesis contributes to the literature by focusing on three dimensions of expertise in classical music improvisation: Skill acquisition, production of improvisation, and transmission of declarative knowledge, skills, and attitudes. In order to document the learning pathways, performance strategies and teaching and learning approaches of expert instrumentalists and pedagogues in Western classical music improvisation, a methodological design in three phases was developed. The research question during the first phase was: What characterizes the learning pathways of Western classical music expert improvisers? To answer this question, interviews were conducted with N = 8 international expert improvisers in Western classical music about their improvisation learning pathways. The second phase aimed to answer the following research question: What strategies are implemented by Western classical music expert improvisers in the course of their performance? An innovative method, based on the retrospective verbal protocol with subjective aided recall data collection strategy was developed to answer this question. N = 5 expert improvisers in Western classical music from the national scene participated in this phase. The third phase of the research was based on the research question: What elements related to the experience, representations, learning pathways, or pedagogical practices of the experts of the domain could help to improve teaching and learning of Western classical music improvisation? In total, N = 15 participants were interviewed during this phase. Among the 15 participants, four were identified as experts in Western classical music improvisation, two as expert pedagogues in Western classical music improvisation and nine as belonging to both categories. The three phases of this doctoral thesis contributed to enriching knowledge about teaching and learning and the production of musical improvisation in the Western classical music context, thus laying the empirical foundations of an effective improvisation teaching practice

Candidate genes revealed by a genome scan for mosquito resistance to a bacterial insecticide: sequence and gene expression variations

<p>Abstract</p> <p>Background</p> <p>Genome scans are becoming an increasingly popular approach to study the genetic basis of adaptation and speciation, but on their own, they are often helpless at identifying the specific gene(s) or mutation(s) targeted by selection. This shortcoming is hopefully bound to disappear in the near future, thanks to the wealth of new genomic resources that are currently being developed for many species. In this article, we provide a foretaste of this exciting new era by conducting a genome scan in the mosquito <it>Aedes aegypti </it>with the aim to look for candidate genes involved in resistance to <it>Bacillus thuringiensis </it>subsp. <it>israelensis </it>(<it>Bti</it>) insecticidal toxins.</p> <p>Results</p> <p>The genome of a <it>Bti</it>-resistant and a <it>Bti</it>-susceptible strains was surveyed using about 500 MITE-based molecular markers, and the loci showing the highest inter-strain genetic differentiation were sequenced and mapped on the <it>Aedes aegypti </it>genome sequence. Several good candidate genes for <it>Bti</it>-resistance were identified in the vicinity of these highly differentiated markers. Two of them, coding for a cadherin and a leucine aminopeptidase, were further examined at the sequence and gene expression levels. In the resistant strain, the cadherin gene displayed patterns of nucleotide polymorphisms consistent with the action of positive selection (e.g. an excess of high compared to intermediate frequency mutations), as well as a significant under-expression compared to the susceptible strain.</p> <p>Conclusion</p> <p>Both sequence and gene expression analyses agree to suggest a role for positive selection in the evolution of this cadherin gene in the resistant strain. However, it is unlikely that resistance to <it>Bti </it>is conferred by this gene alone, and further investigation will be needed to characterize other genes significantly associated with <it>Bti </it>resistance in <it>Ae. aegypti</it>. Beyond these results, this article illustrates how genome scans can build on the body of new genomic information (here, full genome sequence and MITE characterization) to finally hold their promises and help pinpoint candidate genes for adaptation and speciation.</p

A MITE-based genotyping method to reveal hundreds of DNA polymorphisms in an animal genome after a few generations of artificial selection

<p>Abstract</p> <p>Background</p> <p>For most organisms, developing hundreds of genetic markers spanning the whole genome still requires excessive if not unrealistic efforts. In this context, there is an obvious need for methodologies allowing the low-cost, fast and high-throughput genotyping of virtually any species, such as the Diversity Arrays Technology (DArT). One of the crucial steps of the DArT technique is the genome complexity reduction, which allows obtaining a genomic representation characteristic of the studied DNA sample and necessary for subsequent genotyping. In this article, using the mosquito <it>Aedes aegypti </it>as a study model, we describe a new genome complexity reduction method taking advantage of the abundance of miniature inverted repeat transposable elements (MITEs) in the genome of this species.</p> <p>Results</p> <p><it>Ae. aegypti </it>genomic representations were produced following a two-step procedure: (1) restriction digestion of the genomic DNA and simultaneous ligation of a specific adaptor to compatible ends, and (2) amplification of restriction fragments containing a particular MITE element called <it>Pony </it>using two primers, one annealing to the adaptor sequence and one annealing to a conserved sequence motif of the <it>Pony </it>element. Using this protocol, we constructed a library comprising more than 6,000 DArT clones, of which at least 5.70% were highly reliable polymorphic markers for two closely related mosquito strains separated by only a few generations of artificial selection. Within this dataset, linkage disequilibrium was low, and marker redundancy was evaluated at 2.86% only. Most of the detected genetic variability was observed between the two studied mosquito strains, but individuals of the same strain could still be clearly distinguished.</p> <p>Conclusion</p> <p>The new complexity reduction method was particularly efficient to reveal genetic polymorphisms in <it>Ae. egypti</it>. Overall, our results testify of the flexibility of the DArT genotyping technique and open new prospects as regards its application to a wider range of species, including animals which have been refractory to it so far. DArT has also a role to play in the current burst of whole-genome scans carried out in various organisms, which track signatures of selection in order to unravel the basis of genetic adaptation.</p

Metabolic syndrome increases operative mortality in patients undergoing coronary artery bypass grafting surgery

OBJECTIVES: The aim of this study was to determine the impact of the metabolic syndrome (MS) on operative mortality after a coronary artery bypass grafting surgery (CABG). BACKGROUND: Diabetes and obesity are highly prevalent among patients undergoing CABG. However, it remains unclear whether these factors have a significant impact on operative mortality after this procedure. We hypothesized that the metabolic abnormalities associated with MS could negatively influence the operative outcome of CABG surgery. METHODS: We retrospectively analyzed the data of 5,304 consecutive patients who underwent an isolated CABG procedure between 2000 and 2004. Of these 5,304 patients, 2,411 (46%) patients met the National Cholesterol Education Program-Adult Treatment Panel III criteria for MS. The primary end point was operative mortality. RESULTS: The operative mortality after CABG surgery was 2.4% in patients with MS and 0.9% in patients without MS (p < 0.0001). The MS was a strong independent predictor of operative mortality (relative risk 3.04 [95% confidence interval (CI) 1.73 to 5.32], p = 0.0001). After adjusting for other risk factors, the risk of mortality was increased 2.69-fold (95% CI 1.43 to 5.06; p = 0.002) in patients with MS and diabetes and 2.36-fold (95% CI 1.26 to 4.41; p = 0.007) in patients with MS and no diabetes, whereas it was not significantly increased in the patients with diabetes and no MS. CONCLUSIONS: This is the first study to report that MS is a highly prevalent and powerful risk factor for operative mortality in patients undergoing a CABG surgery. Thus, interventions that could contribute to reduce the prevalence of MS in patients with coronary artery disease or that could acutely modify the metabolic perturbations of MS at the time of CABG might substantially improve survival in these patient