Approche de la variabilité du genre Laccaria par l'étude du polymorphisme de longueur des fragments de restriction de l'ADNr

Notice présente dans BelInra (https://belinra.inra.fr/gestion/catalog.php?categ=isbd&id=104920)il s'agit d'un type de produit dont les métadonnées ne correspondent pas aux métadonnées attendues dans les autres types de produit : DISSERTATIONApproche de la variabilité du genre Laccaria par l'étude du polymorphisme de longueur des fragments de restriction de l'ADN

circRNAs Signature as Potential Diagnostic and Prognostic Biomarker for Diabetes Mellitus and Related Cardiovascular Complications

Circular RNAs (circRNAs) belong to the ever-growing class of naturally occurring noncoding RNAs (ncRNAs) molecules. Unlike linear RNA, circRNAs are covalently closed transcripts mostly generated from precursor-mRNA by a non-canonical event called back-splicing. They are highly stable, evolutionarily conserved, and widely distributed in eukaryotes. Some circRNAs are believed to fulfill a variety of functions inside the cell mainly by acting as microRNAs (miRNAs) or RNA-binding proteins (RBPs) sponges. Furthermore, mounting evidence suggests that the misregulation of circRNAs is among the first alterations in various metabolic disorders including obesity, hypertension, and cardiovascular diseases. More recent research has revealed that circRNAs also play a substantial role in the pathogenesis of diabetes mellitus (DM) and related vascular complications. These findings have added a new layer of complexity to our understanding of DM and underscored the need to reexamine the molecular pathways that lead to this disorder in the context of epigenetics and circRNA regulatory mechanisms. Here, I review current knowledge about circRNAs dysregulation in diabetes and describe their potential role as innovative biomarkers to predict diabetes-related cardiovascular (CV) events. Finally, I discuss some of the actual limitations to the promise of these RNA transcripts as emerging therapeutics and provide recommendations for future research on circRNA-based medicine

Dietary Patterns Influence Target Gene Expression through Emerging Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) refers to the pathologic buildup of extra fat in the form of triglycerides in liver cells without excessive alcohol intake. NAFLD became the most common cause of chronic liver disease that is tightly associated with key aspects of metabolic disorders, including insulin resistance, obesity, diabetes, and metabolic syndrome. It is generally accepted that multiple mechanisms and pathways are involved in the pathogenesis of NAFLD. Heredity, sedentary lifestyle, westernized high sugar saturated fat diet, metabolic derangements, and gut microbiota, all may interact on a on genetically susceptible individual to cause the disease initiation and progression. While there is an unquestionable role for gene-diet interaction in the etiopathogenesis of NAFLD, it is increasingly apparent that epigenetic processes can orchestrate many aspects of this interaction and provide additional mechanistic insight. Exciting research demonstrated that epigenetic alterations in chromatin can influence gene expression chiefly at the transcriptional level in response to unbalanced diet, and therefore predispose an individual to NAFLD. Thus, further discoveries into molecular epigenetic mechanisms underlying the link between nutrition and aberrant hepatic gene expression can yield new insights into the pathogenesis of NAFLD, and allow innovative epigenetic-based strategies for its early prevention and targeted therapies. Herein, we outline the current knowledge of the interactive role of a high-fat high-calories diet and gene expression through DNA methylation and histone modifications on the pathogenesis of NAFLD. We also provide perspectives on the advancement of the epigenomics in the field and possible shortcomings and limitations ahead

Molecular Links between Cancer and Metabolic Diseases: New Perspectives and Therapeutic Strategies for Cancer Prevention and Treatment by Targeting Nutritional Patterns and Metabolic Alterations

Cancer-related mortality is reported to be elevated in cases with metabolic dysfunction [...

Epigenetic Regulation of ATP-Binding Cassette Protein A1 (ABCA1) Gene Expression: A New Era to Alleviate Atherosclerotic Cardiovascular Disease

The most important function of high density lipoprotein (HDL) is its ability to remove cholesterol from cells and tissues involved in the early stages of atherosclerosis back to the liver for excretion. The ATP-binding cassette transporters ABCA1 and ABCG1 are responsible for the major part of cholesterol efflux to HDL in macrophage foam cells. Thus, promoting the process of reverse cholesterol transport (RCT) by upregulating mainly ABCA1 remains one of the potential targets for the development of new therapeutic agents against atherosclerosis. Growing evidence suggests that posttranscriptional regulation of HDL biogenesis as well as modulation of ABCA1 expression are under the control of several genetic and epigenetic factors such as transcription factor (TFs), microRNAs (miRNAs) and RNA-binding proteins (RBPs).These factors may act either individually or in combination to orchestrate ABCA1 expression. Complementary to our recent work, we propose an exploratory model for the potential molecular mechanism(s) underlying epigenetic signature of ABCA1 gene regulation. Such a model may hopefully provide the basic framework for understanding the epigenetic regulation of RCT and contribute to the development of novel therapeutic strategies to alleviate the burden of cardiovascular diseases (CVD)

Peptides antimicrobiens (un lien entre l'immuno-inflammation et les facteurs de risque du syndrome métabolique et des maladies cardiovasculaires)

Les maladies cardiovasculaires (MCV) sont des affections immuno-inflammatoires chroniques qui sont liées à de nombreux facteurs de risque. Les défensines et les cathélicidines sont des peptides antimicrobiens considérés comme des effecteurs clés de l'immunité innée, mais aussi des réponses inflammatoires. Il a été postulé que ces peptides sont impliqués dans le développement de l'athérosclérose. Afin de vérifier cette hypothèse, nous avons étudié l'expression des gènes de la cathélicidine LL-37 et des défensines-a DEFA1-3 dans les cellules mononuclées du sang périphérique (PBMCs) dans la cohorte Stanislas. Nous avons démontré que l'expression des ARNm de ces gènes est significativement corrélée avec les indicateurs de risque des MCV, à savoir l'obésité, la pression artérielle, les taux circulants des triglycérides et du glucose, l'hypo-HDL-C et les leucocytes. De plus, des taux élevés des ARNm de ces gènes sont associés au syndrome métabolique. Nous avons aussi démontré que l'expression des gènes des DEFA1-3 et de LL-37 est corrélée avec celle du récepteur chimio-attractant FPR et que le génotype TT du polymorphisme FPR1 c.32C>T est associé à une diminution des taux circulants de la E-sélectine, suggérant que ces peptides pourraient agir via FPR et que le polymorphisme c.32C>T affecte la fonction endothéliale. Enfin, nos études in vitro ont montré que l'expression des gènes des DEFA1-3 et de CRAMP, cathélicidine de la souris, est modulée par le glucose et l'insuline, respectivement dans les neutrophiles HL-60 et les adipocytes 3T3-L1. L'ensemble de ces études suggère que les DEFA1-3 et LL-37 pourraient constituer un lien entre le système immunitaire inné et le risque des MCV et du syndrome métabolique.Multiple risk factors for atherosclerosis and cardiovascular diseases (CVD) act in a synergistic way through inflammatory pathways. Most of CVD risk factors stimulate the release of inflammatory mediators. Defensins and cathelicidins are antimicrobial peptides (AMPs) produced mainly by inflammatory cells. Beside their role in host defense, AMPs are also considered as effectors of inflammatory responses. They have been suggested to play a role in atherosclerosis. To verify this hypothesis, we studied a-defensins DEFA1-3 and cathelicidin LL-37 in a sample of the STANISLAS cohort. We demonstrated that mRNA levels of LL-37 and DEFA1-3 genes in peripheral blood mononuclear cells (PBMCs) of studied subjects are significantly correlated with indicators of obesity, blood pressure, circulating triglycerides and fasting glucose levels, hypo-HDL-C, and leukocytes counts suggesting a role of these genes in CVD. Further analysis revealed that high expression of these genes might be associated with metabolic syndrome. We also showed that expression of LL-37 and DEFA1-3 genes was positively associated with that of FPR receptor gene and that the TT genotype of FPR1 c.32C>T/I11T polymorphism was significantly associated with decreased levels of soluble E-selectin suggesting that these peptides may act through this receptor and such a polymorphism may has an impact on endothelial cells function. In an in vitro model, we found that glucose and insulin modulate the expression of DEFA1-3 and CRAMP cathelicidin genes in human HL-60 neutrophils and mouse 3T3-L1 adipocytes cell lines, respectively. Together, our studies demonstrated that DEFA1-3 and LL-37 could be a potential link between innate immunity and CVD and metabolic syndrome.NANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Antimicrobial and Protease Inhibitory Functions of the Human Cathelicidin (hCAP18/LL-37) Prosequence

Cathelicidins are a class of small cationic peptide antibiotics that are expressed in skin and in other epithelial cells and are an active component of mammalian innate immunity. Human cathelicidin (hCAP18/LL-37) consists of a conserved prosequence called the cathelin-like domain and a C-terminal peptide named LL-37. To date, our understanding of the cathelin-like domain was very limited. To bring insight into the function of this evolutionarily conserved prosequence, we produced recombinant human cathelin-like protein and full-length hCAP18/LL-37 in Escherichia coli. As the cathelin-like protein shares homology with the cystatin family of cysteine protease inhibitors, we first analyzed the effect of the cathelin-like recombinant protein on the cysteine protease cathepsin L. We found that the cathelin-like protein inhibited protease activity. Next, we tested the cathelin-like protein for antimicrobial activity using solid phase radial diffusion and liquid phase killing assays. The cathelin-like prosequence, but not full-length hCAP18/LL-37, killed human pathogens including E. coli and methicillin-resistant Staphylococcus aureus at concentrations ranging from 16 to 32 μM. Together these findings suggest that after proteolytic cleavage the cathelin-like domain can contribute to innate host defense through inhibition of bacterial growth and limitation of cysteine-proteinase-mediated tissue damage. As these dual functions are complementary to the LL-37 peptide released from the C-terminus of full-length hCAP18/LL-37, human cathelicidin represents an elegant multifunctional effector molecule for innate immune defense of the skin

Marches quantiques pour déterminer les scénarios de défaillance d'un système

International audienceLa recherche des scénarios de défaillance d'un système est un problème bien connu dans le monde industriel, et il peut être résolu en recherchant les chemins dans le graphe des états de ce système. La difficulté réside dans le fait qu'on ne cherche pas un seul ou une partie de ces chemins, on cherche tous ces chemins. Dans ce papier, on propose notre approche quantique afin de trouver tous les chemins dans ce graphe des états entre un sommet source et les sommets marquants. Notre approche se base sur les marches quantiques pour déterminer tous les chemins possibles au lieu de les traiter un par un classiquement, aussi notre approche est capable de déterminer tous ces chemins dans le même temps avec seulement ⌈ K×n ln 2 ⌉ + n qubits et n+2 oracles pour le cas où on essaie de déterminer seulement les scénarios avec des défaillances et les scénarios avec une possibilité d'une seule réparation durant la période du scénario. Nous avons testé notre approche sur le graphe des états d'un petit système de quatre composants et nous avons pu trouver tous les scénarios de défaillance de ce système. Malheureusement, nous ne pouvons pas tester sur des grands systèmes en raison du nombre des qubits disponibles aujourd'hui dans les ordinateurs quantiques, ce qui limite ce travail dans le cas d'utilisation. Le but de ce papier est de préparer une version quantique qui permet de résoudre ce problème dans l'attente de la mise à l'échelle des ordinateurs quantiques

Quantum Approach for Vertex Separator Problem in Directed Graphs

Part 7: Explainable AI/Graph Representation and Processing FrameworksInternational audienceThe Vertex Separator Problem of a directed graph consists in finding all combinations of vertices which can disconnect the source and the terminal of the graph, these combinations are minimal if they contain only the minimal number of vertices. In this paper, we introduce a new quantum algorithm based on a movement strategy to find these separators in a quantum superposition with linear complexity. Our algorithm has been tested on small directed graphs using a real Quantum Computer made by IBM

Le calcul quantique pour la sûreté de fonctionnement : une perspective

International audienceLes Etudes Probabilistes de Sûreté semblent faire partie des problèmes à forte combinatoire pouvant être un candidat intéressant pour le calcul quantique. Dans ce papier, nous donnons une perspective de ce que pourraient devenir les algorithmes de calculs dans le domaine des EPS. Différentes classes d'algorithmes quantiques pourraient être envisagées dans ce sens et contribuer non seulement changer notre façon de calculer les métriques de sûreté de fonctionnement dans de grands modèles, mais aussi impacter les applications industrielles supportées par ces méthodes