Neuromatch Academy: a 3-week, online summer school in computational neuroscience

Neuromatch Academy (https://academy.neuromatch.io; (van Viegen et al., 2021)) was designed as an online summer school to cover the basics of computational neuroscience in three weeks. The materials cover dominant and emerging computational neuroscience tools, how they complement one another, and specifically focus on how they can help us to better understand how the brain functions. An original component of the materials is its focus on modeling choices, i.e. how do we choose the right approach, how do we build models, and how can we evaluate models to determine if they provide real (meaningful) insight. This meta-modeling component of the instructional materials asks what questions can be answered by different techniques, and how to apply them meaningfully to get insight about brain function

Cleft lip-palate : Genetic-etiologic approach and role of gene expression in angiogenesis. Development of an vivo study model in children.

Les fentes labio-palatines (FLP) sont la malformation cranio-faciale congénitale la plus fréquente. D'origine multifactorielle, elles sont la conséquence d'un défaut de fusion des bourgeons faciaux.Objectif et MéthodologieL'objectif de ce travail a été d'étudier la place des gènes de l'angiogenèse dans le cadre de la piste étiologique des FL/P. La méthodologie de ce travail comportait 3 étapes :- Une analyse systématique et exhaustive des gènes impliqués dans les FL/P comprenant les gènes identifiés mais aussi les gènes potentiellement impliqués.- Une analyse rétrospective des explorations génétiques des FL/P opérées au CHU de Reims entre 2003 et 2009.- La mise en place d'une analyse prospective (2009-2012, AOL) :- Génomique constitutionnelle par CGH Array- In situ au niveau des berges des fentes issues de déchets opératoires des chirurgies primaires des FL/P comprenant :Le développement d'un protocole de culture cellulaire de fibroblastesUne analyse anatomopathologiqueEt surtout le développement d'un modèle d'étude in vivo chez l'enfant d'analyse d'expression des gènes de l'angiogenèse.RésultatsL'analyse systématique des gènes impliqués dans les FL/P a mis en évidence 95 gènes dont plus d'une dizaine sont connus comme liés aux mécanismes d'angiogenèse (facteurs de croissance et protéases). Ces derniers sont en interaction entre eux mais aussi avec 18 autres gènes impliqués eux aussi dans les FL/P. Ainsi au total 1/3 des gènes d'intérêt sont soit des gènes de l'angiogenèse soit en lien avec eux.L'étude rétrospective nous a permis de mettre en exergue certaines formes cliniques originales qui ont été étudiées et publiées sous un angle « étiologique ».L'étude prospective nous a permis, après obtention des consentements, d'inclure 72 patients (30 FLP, 24FL, 18FP) opérés au CHU de Reims entre 2009 et 2012 d'une chirurgie primaire.Nous présentons :- nos résultats anatomopathologiques, et génétiques (CGH Array)- notre protocole de culture cellulaire- nos réflexions, notre cheminement aboutissant à la création du modèle d'étude d'analyse d'expression des gènes de l'angiogenèseDiscussionLa littérature a bien mis en avant une implication des phénomènes angiogéniques dans la constitution des FL/P par le biais des facteurs de croissance (TGFβ, PDGF C et Ra, FGF, TGFA, FGFR1, FGFR2 ; VEGF) et des protéases (MMP/TIMP2). L'ensemble de nos manipulations in situ nous permet aujourd'hui de disposer du matériel nécessaire pour l'étude de l'expression des facteurs impliqués dans l'angiogenèse sur les berges des fentes.Parallèlement, l'étude génomique constitutionnelle en CGH Array a permis de retrouver des variations non-connues comme polymorphiques chez 62% de nos patients. Des études familiales vont compléter notre travail. Elles permettront de savoir si ces CNV sont héritées ou De Novo et ainsi de préciser leur caractère bénin ou pathologique. L'identification chez un de nos patients d'une amplification, même de petite taille, du gène SKI (gène lié à la voie des TGFβ) nous encourage dans la poursuite de nos recherches d'anomalies constitutionnelles des gènes de l'angiogenèse dans les FL/PLa CGH array est une technique qui nous a paru particulièrement utile et fiable en terme de « scanning » et de dépistage.En conclusion, en pratique clinique, la découverte des anomalies préalablement certainement sous estimées par les cliniciens doit nous mener à une nouvelle réflexion sur le conseil génétique et sur l'utilité dans l'avenir d'un dépistage plus systématique.Cleft lip and palate (CLP) are the most common congenital craniofacial malformation. They have a multifactorial etiology and are the consequence of incomplete fusion of the facial buds.Objective and MethodologyThe objective of this work was to study the role of the genes of angiogenesis in the framework of studying the etiology of CL/P. Our methodological approach included 3 steps:- Systematic and thorough analysis of the genes involved in CL/P including identified genes but also genes that could be potentially involved.- A retrospective analysis of the operated clefts at the University Hospital of Reims between 2003 and 2009.- Implementation of a prospective analysis (2009-2012, AOL):- Constitutional genomic study by CGH Array- In situ with tissue specimens extracted from surgically excised cleft edges including:The development of a protocol for fibroblast cell culturesHistopathological analysisAnd above all the development of an in vivo study model in children for analyzing the expression of genes of angiogenesis.ResultsThe systemic analysis of genes involved in cleft lip palate unveiled 95 genes including about ten that are known to be related to angiogenesis mechanisms (growth factor and proteases). These genes interact between themselves but also with 18 other genes also involved in CL/P. In all, 1/3 of relevant genes are either angiogenesis-related genes or in direct relation with them.The retrospective study permitted to underline the some original clinical forms that were studied and published under an « etiological » angle.The prospective study included 72 patients (30 CLP, 24CL, 18CP), for whom we obtained informed signed consents, operated at the University Hospital of Reims between 2009 and 2012 for primary cleft surgery.We present:- Our histopathological and genetic results (CGH Array)- Our cell culture protocol (submitted for publication)- Our approaches and thought process behind the design of a study model for analyzing expression profiling of angiogenic genesDiscussionThe literature has highlighted the role of angiogenesis in the formation of cleft lip/palate via growth factors (TGFβ, PDGF C and Ra, FGF, TGFA, FGFR1, FGFR2, VEGF) and proteases (MMP/TIMP2). All our manipulations in situ have yielded the necessary material, i.e. edges of resected clefts, to study the expression of factors involved in cleft angiogenesis.In parallel, the constitutional genomic study in CGH Array enabled to uncover abnormalities in 62% of our patients. Family studies will complete our work. They will help to refine if these CNV are inherited or de novo and thus indicate their benign or pathological nature. In one of our patients, the identification of the SKI gene (related to the TGFβ pathway) encourages us to continue our research of genetic abnormalities of angiogenic genes involved in cleft lip/palate. CGH array appeared to be a very useful and reliable method in terms of scanning and screening.In conclusion, in clinical practice, the discovery of abnormalities which were probably underestimated by clinicians before, leads us to rethink the issue of genetic counseling and the relevance of a more systematic screening for these abnormalities in the future

Furlow / Staphylorraphie (résultats chirurgicaux et orthophoniques d'une série rétrospective de 44 fentes vélaires)

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Four-Week Low-Glycemic index Breakfast With a Modest Amount of Soluble Fibers

Low-glycemic index diets are associated with a wide range of benefits when followed on a chronic basis. The chronic effects, however, of the substitution of 1 meal per day are not well known in diabetic subjects. Therefore, we aimed to evaluate whether the chronic use of a low-glycemic index breakfast (low-GIB) rich in low-GI carbohydrates and a modest amount of soluble fibers could have an effect on lipemia at a subsequent lunch, and improve glucose and lipid metabolism in men with type 2 diabetes. A total of 13 men with type 2 diabetes were randomly allocated in a double-blind cross-over design to a 4-week daily intake of a low-GI versus a high-GI breakfast separated by a 15-day washout interval. The low-GI breakfast was composed of whole grain bread and muesli containing 3 g ␤-glucan from oats. Low-GIB induced lower postprandial plasma glucose peaks than the high-GIB at the beginning (baseline, P < .001) and after the 4-week intake (P < .001). The incremental area under the plasma glucose curve was also lower (P < .001, P < .01, baseline, and 4 weeks, respectively). There was no effect on fasting plasma glucose, insulin, fructosamine, or glycosylated hemoglobin (HbA 1c ). Fasting plasma cholesterol, as well as the incremental area under the cholesterol curve, were lower (P < .03, P < .02) after the 4-week low-GIB period than after the high-GIB period. Apolipoprotein B (apo B) was also decreased by the 4-week low-GIB. There was no effect of the low-GI breakfast on triacylglycerol excursions or glucose and insulin responses at the second meal. The high-GIB, however, tended to decrease the amount of mRNA of leptin in abdominal adipose tissue, but had no effect on peroxisome proliferatoractivated receptor ␥ (PPAR␥) and cholesterylester transfer protein (CETP) mRNA amounts. In conclusion, the intake of a low-GI breakfast containing a modest amount (3 g) of ␤-glucan for 4 weeks allowed good glycemic control and induced low plasma cholesterol levels in men with type 2 diabetes. The decrease in plasma cholesterol associated with low-GI breakfast intake may reduce the risk of developing cardiovascular complications in subjects with type 2 diabetes. Copyright 2002, Elsevier Science (USA). All rights reserved. C ONCERNS ABOUT USING high-carbohydrate diets in diabetes 1 because of adverse effects on triglycerides and high-density lipoprotein-cholesterol levels, 2 are overcome by recommending carbohydrates that give low postprandial plasma glucose responses. 3,4 For over half a century, it has been postulated that the increase in blood glucose was less pronounced after the consumption of starchy foods than after the consumption of foods containing simple carbohydrates. Starchy foods have been recognized as the main candidate for reducing glycemic and insulinemic responses. However, coincidental with recommendations to increase the intake of starchy foods has been the recognition that the glycemic responses to all starches are not the same and that starches are not interchangeable. Although the use of low-GI carbohydrates in the diet of patients with type 2 diabetes is still debated, The acute effects of low-or high-GI breakfasts have been evaluated in normal healthy subjects. Few studies have evaluated the chronic effect of these breakfasts in type 2 diabetic subjects. 21,22 In this perspective, therefore, we aimed to evaluate the effects of a low-GI breakfast on both glucose and lipid metabolism in men with type 2 diabetes. We aimed also to evaluate the effects of a low-GI breakfast on hyperlipidemia at a subsequent lunch. Furthermore, we determined the expression of some lipid-related enzymes: cholesterylester transfer protein (CETP), leptin, and peroxisome proliferator-activated receptor ␥ (PPAR␥), because in a previous study from our laboratory, a similar diet for rats was found to decrease the satietogenic factor, leptin, as well as some lipid-related enzymes. 2

Caractérisation par NRA de l’oxygène présent dans des échantillons de carbure d’uranium – Aide à l’optimisation de la fabrication

International audienc

Chlorine in wadsleyite and ringwoodite: An experimental study

International audienceWe report concentrations of Chlorine (Cl) in synthetic wadsleyite (Wd) and ringwoodite (Rw) in the system NaCl–(Mg, Fe)2SiO4 under hydrous and anhydrous conditions. Multi-anvil press experiments were performed under pressures (14–22 GPa) and temperatures (1100–1400 °C) relevant to the transition zone (TZ: 410–670 km depth). Cl and H contents were measured using Particle Induced X-ray Emission (PIXE) and Elastic Recoil Detection Analysis (ERDA) respectively. Results show that Cl content in Rw and Wd is significantly higher than in other nominally anhydrous minerals from the upper mantle (olivine, pyroxene, garnet), with up to 490 ppm Cl in anhydrous Rw, and from 174 to 200 ppm Cl in hydrous Wd and up to 113 ppm Cl in hydrous Rw

Is the transition zone a deep reservoir for fluorine?

International audienceIt is now recognized that the transition zone (TZ) is a significant repository for water. This means that other volatile species may also be stored in this region such as halogen elements. We have measured the solubility of fluorine in wadsleyite (Wd) and ringwoodite (Rw) under hydrous and anhydrous conditions at different pressures and temperatures, relevant for the transition zone. F contents are similar in Wd (665 to 1045 ppm F, up to 956 ppm H2O) and in Rw (186 to 1235 ppm F, up to 1404 ppm H2O). This suggests that F may be incorporated in the same manner as water in the major nominally anhydrous minerals of the TZ: ringwoodite and wadsleyite and that the transition zone could be a major reservoir for fluorine. In the framework of the “water filter model” proposed by Bercovici and Karato (2003), the contrast of volatile element contents between a depleted upper mantle and an enriched transition zone could be maintained over geological time scales. Previous estimates of the fluorine content of the Bulk Silicate Earth (BSE), such as 25 ppm by mass (McDonough and Sun, 1995), have assumed a homogeneous mantle. Although we do not know whether the TZ is F saturated or not, we used our new experimental data and estimates of the lower mantle F content from ocean island basalts to estimate a maximum BSE fluorine content of 59 ppm by mass for a hydrous, F-saturated TZ. This upper bound on the range of possible BSE F content emphasizes the challenges when explaining the origin of volatile elements in the Earth from a carbonaceous chondrite late veneer