Implémentation par automates cellulaires d'une modélisation architecturale de rétine biologique

Cet article traite de l'implémentation sur calculateur classique d'une modélisation cellulaire de la rétine biologique via deux mod`eles d'automates cellulaires (2D et 3D). Les algorithmes utilisés dans cet objectif, pénalisants en temps de calcul, nécessitent la plupart du temps une architecture de traitement spécifique et par conséquent, une adaptation de l'algorithme. Notre solution alternative utilise les fonctionnalités de composants logiciels de synthèse d'images enfouissables en partie dans la carte graphique pour permettre la parallélisation des traitements cellulaires

Lessons From the First Comprehensive Molecular Characterization of Cell Cycle Control in Rodent Insulinoma Cell Lines

OBJECTIVE—Rodent insulinoma cell lines may serve as a model for designing continuously replicating human β-cell lines and provide clues as to the central cell cycle regulatory molecules in the β-cell

Loss of Sugar Detection by GLUT2 Affects Glucose Homeostasis in Mice

International audienceBACKGROUND: Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from glucose metabolism. Here, we studied the detection of extracellular glucose concentrations in vivo by invalidating the transduction pathway downstream from the transporter-detector GLUT2 and measured the physiological impact of this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We produced mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking glucose-mediated gene expression in vitro without affecting glucose metabolism. Impairment of GLUT2-mediated sugar detection transiently protected transgenic mice against starvation and streptozotocin-induced diabetes, suggesting that both low- and high-glucose concentrations were not detected. Transgenic mice favored lipid oxidation, and oral glucose was slowly cleared from blood due to low insulin production, despite massive urinary glucose excretion. Kidney adaptation was characterized by a lower rate of glucose reabsorption, whereas pancreatic adaptation was associated with a larger number of small islets. CONCLUSIONS/SIGNIFICANCE: Molecular invalidation of sugar sensing in GLUT2-loop transgenic mice changed multiple aspects of glucose homeostasis, highlighting by a top-down approach, the role of membrane glucose receptors as potential therapeutic targets

Transgenic Overexpression of Active Calcineurin in β-Cells Results in Decreased β-Cell Mass and Hyperglycemia

BACKGROUND:Glucose modulates beta-cell mass and function through an initial depolarization and Ca(2+) influx, which then triggers a number of growth regulating signaling pathways. One of the most important downstream effectors in Ca(2+) signaling is the calcium/Calmodulin activated serine threonine phosphatase, calcineurin. Recent evidence suggests that calcineurin/NFAT is essential for beta-cell proliferation, and that in its absence loss of beta-cells results in diabetes. We hypothesized that in contrast, activation of calcineurin might result in expansion of beta-cell mass and resistance to diabetes. METHODOLOGY/PRINCIPAL FINDINGS:To determine the role of activation of calcineurin signaling in the regulation of pancreatic beta-cell mass and proliferation, we created mice that expressed a constitutively active form of calcineurin under the insulin gene promoter (caCn(RIP)). To our surprise, these mice exhibited glucose intolerance. In vitro studies demonstrated that while the second phase of Insulin secretion is enhanced, the overall insulin secretory response was conserved. Islet morphometric studies demonstrated decreased beta-cell mass suggesting that this was a major component responsible for altered Insulin secretion and glucose intolerance in caCn(RIP) mice. The reduced beta-cell mass was accompanied by decreased proliferation and enhanced apoptosis. CONCLUSIONS:Our studies identify calcineurin as an important factor in controlling glucose homeostasis and indicate that chronic depolarization leading to increased calcineurin activity may contribute, along with other genetic and environmental factors, to beta-cell dysfunction and diabetes

The Incidence of Pulmonary Embolism and Associated FDG-PET Findings in IV Contrast-Enhanced PET/CT

Rationale and objectivesMost fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography with computed tomography (PET/CT) studies are performed on cancer patients. These patients are at increased risk of pulmonary embolism (PE). In this retrospective review, we determined the rate of PE, and the prevalence of associated FDG-PET findings on intravenous (IV) contrast-enhanced PET/CT.Materials and methodsWe identified all PET/CT studies performed at our institution with a reported finding of PE between January 2005 and October 2012. The medical record was reviewed for symptoms, which were identified after the diagnosis of PE, and whether the patients received treatment. The prevalence of associated FDG-PET findings was determined.ResultsA total of 65 total cases of PE (of 182,72 total PET/CT examinations) were identified of which 59 were previously unknown. This gives an incidental PE (IPE) rate of 0.32%. Of the patients where sufficient clinical information was available, 34 of 36 (94%) were treated either with therapeutic anticoagulation or inferior vena cava filter, and 30 of 36 (83%) were asymptomatic in retrospect. Of the patients with IPE, we found nine (15.2%) with associated focal pulmonary artery hypermetabolism, three (5.1%) with hypermetabolic pulmonary infarction, and one with increased isolated right ventricular FDG uptake (1.7%). One case of chronic PE demonstrated a focal hypometabolic filling defect in a pulmonary artery on PET.ConclusionsWe found IPE in 0.32% of PET/CT scans. Focal pulmonary artery hypermetabolism or hypometabolism, and hypermetabolic pulmonary artery infarction with the "rim sign" were uncommonly associated with PE. These findings could raise the possibility of IPE in non-IV contrast-enhanced PET/CT studies

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Realisation de deux capteurs de controle non destructif en traitement d'images et en emission ultrasonore

SIGLECNRS T 55394 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Architectural model of a biological retina using cellular automata

International audienceDevelopments in neurophysiology focusing on foveal vision have characterized more and more precisely the spatiotemporal processing that is well adapted to the regularization of the visual information within the retina. The works described in this article focus on a simplified architec-tural model based on features and mechanisms of adaptation in the retina. Similarly to the bio-logical retina, which transforms luminance information into a series of encoded representations of image characteristics transmitted to the brain, our structural model allows us to reveal more information in the scene. Our modeling of the different functional pathways permits the mapping of important complementary information types at abstract levels of image analysis, and thereby allows a better exploitation of visual clues. Our model is based on a distributed cellular automata network and simulates the retinal processing of stimuli that are stationary or in motion. Thanks to its capacity for dynamic adaptation, our model can adapt itself to different scenes (e.g., bright and dim, stationary and moving, etc.) and can parallelize those processing steps that can be supported by parallel calculators