Three-dimensional modeling of a thermal dendrite using the phase field method with automatic anisotropic and unstructured adaptive finite element meshing

International audienceDendritic growth is computed with automatic adaptation of an anisotropic and unstructured finite element mesh. The energy conservation equation is formulated for solid and liquid phases considering an interface balance that includes the Gibbs-Thomson effect. An equation for a diffuse interface is also developed by considering a phase field function with constant negative value in the liquid and constant positive value in the solid. Unknowns are the phase field function and a dimensionless temperature, as proposed by [1]. Linear finite element interpolation is used for both variables, and discretization stabilization techniques ensure convergence towards a correct non-oscillating solution. In order to perform quantitative computations of dendritic growth on a large domain, two additional numerical ingredients are necessary: automatic anisotropic unstructured adaptive meshing [2,[3] and parallel implementations [4], both made available with the numerical platform used (CimLib) based on C++ developments. Mesh adaptation is found to greatly reduce the number of degrees of freedom. Results of phase field simulations for dendritic solidification of a pure material in two and three dimensions are shown and compared with reference work [1]. Discussion on algorithm details and the CPU time will be outlined

Nogo-A Regulates Neural Precursor Migration in the Embryonic Mouse Cortex

Although Nogo-A has been intensively studied for its inhibitory effect on axonal regeneration in the adult central nervous system, little is known about its function during brain development. In the embryonic mouse cortex, Nogo-A is expressed by radial precursor/glial cells and by tangentially migrating as well as postmigratory neurons. We studied radially migrating neuroblasts in wild-type and Nogo-A knockout (KO) mouse embryos. In vitro analysis showed that Nogo-A and its receptor components NgR, Lingo-1, TROY, and p75 are expressed in cells emigrating from embryonic forebrain–derived neurospheres. Live imaging revealed an increased cell motility when Nogo-A was knocked out or blocked with antibodies. Antibodies blocking NgR or Lingo-1 showed the same motility-enhancing effect supporting a direct role of surface Nogo-A on migration. Bromodeoxyuridine (BrdU) labeling of embryonic day (E)15.5 embryos demonstrated that Nogo-A influences the radial migration of neuronal precursors. At E17.5, the normal transient accumulation of radially migrating precursors within the subventricular zone was not detectable in the Nogo-A KO mouse cortex. At E19, migration to the upper cortical layers was disturbed. These findings suggest that Nogo-A and its receptor complex play a role in the interplay of adhesive and repulsive cell interactions in radial migration during cortical development

Differential contribution of APP metabolites to early cognitive deficits in a TgCRND8 mouse model of Alzheimer’s disease

International audienceAlzheimer's disease (AD) is a neurodegenerative pathology commonly characterized by a progressive and irreversible deterioration of cognitive functions, especially memory. Although the etiology of AD remains unknown , a consensus has emerged on the amyloid hypothesis, which posits that increased production of soluble amyloid b (Ab) peptide induces neuronal network dysfunctions and cognitive deficits. However, the relative failures of Ab-centric therapeutics suggest that the amyloid hypothesis is incomplete and/or that the treatments were given too late in the course of AD, when neuronal damages were already too extensive. Hence, it is striking to see that very few studies have extensively characterized, from anatomy to behavior, the alterations associated with pre-amyloid stages in mouse models of AD amyloid pathology. To fulfill this gap, we examined memory capacities as well as hippocampal network anatomy and dynamics in young adult pre-plaque TgCRND8 mice when hippocampal Ab levels are still low. We showed that TgCRND8 mice present alterations in hippocampal inhibitory networks and g oscillations at this stage. Further, these mice exhibited deficits only in a subset of hippocampal-dependent memory tasks, which are all affected at later stages. Last, using a pharmacological approach, we showed that some of these early memory deficits were Ab-independent. Our results could partly explain the limited efficacy of Ab-directed treatments and favor multitherapy approaches for early symptomatic treatment for AD

Understanding the limits of animal models as predictors of human biology: lessons learned from the sbv IMPROVER Species Translation Challenge

Motivation: Inferring how humans respond to external cues such as drugs, chemicals, viruses or hormones is an essential question in biomedicine. Very often, however, this question cannot be addressed because it is not possible to perform experiments in humans. A reasonable alternative consists of generating responses in animal models and ‘translating' those results to humans. The limitations of such translation, however, are far from clear, and systematic assessments of its actual potential are urgently needed. sbv IMPROVER (systems biology verification for Industrial Methodology for PROcess VErification in Research) was designed as a series of challenges to address translatability between humans and rodents. This collaborative crowd-sourcing initiative invited scientists from around the world to apply their own computational methodologies on a multilayer systems biology dataset composed of phosphoproteomics, transcriptomics and cytokine data derived from normal human and rat bronchial epithelial cells exposed in parallel to 52 different stimuli under identical conditions. Our aim was to understand the limits of species-to-species translatability at different levels of biological organization: signaling, transcriptional and release of secreted factors (such as cytokines). Participating teams submitted 49 different solutions across the sub-challenges, two-thirds of which were statistically significantly better than random. Additionally, similar computational methods were found to range widely in their performance within the same challenge, and no single method emerged as a clear winner across all sub-challenges. Finally, computational methods were able to effectively translate some specific stimuli and biological processes in the lung epithelial system, such as DNA synthesis, cytoskeleton and extracellular matrix, translation, immune/inflammation and growth factor/proliferation pathways, better than the expected response similarity between species. Contact: [email protected] or [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

Construction of a computable cell proliferation network focused on non-diseased lung cells

<p>Abstract</p> <p>Background</p> <p>Critical to advancing the systems-level evaluation of complex biological processes is the development of comprehensive networks and computational methods to apply to the analysis of systems biology data (transcriptomics, proteomics/phosphoproteomics, metabolomics, etc.). Ideally, these networks will be specifically designed to capture the normal, non-diseased biology of the tissue or cell types under investigation, and can be used with experimentally generated systems biology data to assess the biological impact of perturbations like xenobiotics and other cellular stresses. Lung cell proliferation is a key biological process to capture in such a network model, given the pivotal role that proliferation plays in lung diseases including cancer, chronic obstructive pulmonary disease (COPD), and fibrosis. Unfortunately, no such network has been available prior to this work.</p> <p>Results</p> <p>To further a systems-level assessment of the biological impact of perturbations on non-diseased mammalian lung cells, we constructed a lung-focused network for cell proliferation. The network encompasses diverse biological areas that lead to the regulation of normal lung cell proliferation (Cell Cycle, Growth Factors, Cell Interaction, Intra- and Extracellular Signaling, and Epigenetics), and contains a total of 848 nodes (biological entities) and 1597 edges (relationships between biological entities). The network was verified using four published gene expression profiling data sets associated with measured cell proliferation endpoints in lung and lung-related cell types. Predicted changes in the activity of core machinery involved in cell cycle regulation (RB1, CDKN1A, and MYC/MYCN) are statistically supported across multiple data sets, underscoring the general applicability of this approach for a network-wide biological impact assessment using systems biology data.</p> <p>Conclusions</p> <p>To the best of our knowledge, this lung-focused Cell Proliferation Network provides the most comprehensive connectivity map in existence of the molecular mechanisms regulating cell proliferation in the lung. The network is based on fully referenced causal relationships obtained from extensive evaluation of the literature. The computable structure of the network enables its application to the qualitative and quantitative evaluation of cell proliferation using systems biology data sets. The network is available for public use.</p

Exploring the clinical features of narcolepsy type 1 versus narcolepsy type 2 from European Narcolepsy Network database with machine learning

Narcolepsy is a rare life-long disease that exists in two forms, narcolepsy type-1 (NT1) or type-2 (NT2), but only NT1 is accepted as clearly defined entity. Both types of narcolepsies belong to the group of central hypersomnias (CH), a spectrum of poorly defined diseases with excessive daytime sleepiness as a core feature. Due to the considerable overlap of symptoms and the rarity of the diseases, it is difficult to identify distinct phenotypes of CH. Machine learning (ML) can help to identify phenotypes as it learns to recognize clinical features invisible for humans. Here we apply ML to data from the huge European Narcolepsy Network (EU-NN) that contains hundreds of mixed features of narcolepsy making it difficult to analyze with classical statistics. Stochastic gradient boosting, a supervised learning model with built-in feature selection, results in high performances in testing set. While cataplexy features are recognized as the most influential predictors, machine find additional features, e.g. mean rapid-eye-movement sleep latency of multiple sleep latency test contributes to classify NT1 and NT2 as confirmed by classical statistical analysis. Our results suggest ML can identify features of CH on machine scale from complex databases, thus providing 'ideas' and promising candidates for future diagnostic classifications.</p

Development and evaluation of robust molecular markers linked to disease resistance in tomato for distinctness, uniformity and stability testing

Molecular markers linked to phenotypically important traits are of great interest especially when traits are difficult and/or costly to be observed. In tomato where a strong focus on resistance breeding has led to the introgression of several resistance genes, resistance traits have become important characteristics in distinctness, uniformity and stability (DUS) testing for Plant Breeders Rights (PBR) applications. Evaluation of disease traits in biological assays is not always straightforward because assays are often influenced by environmental factors, and difficulties in scoring exist. In this study, we describe the development and/or evaluation of molecular marker assays for the Verticillium genes Ve1 and Ve2, the tomato mosaic virusTm1 (linked marker), the tomato mosaic virus Tm2 and Tm22 genes, the Meloidogyne incognita Mi1-2 gene, the Fusarium I (linked marker) and I2 loci, which are obligatory traits in PBR testing. The marker assays were evaluated for their robustness in a ring test and then evaluated in a set of varieties. Although in general, results between biological assays and marker assays gave highly correlated results, marker assays showed an advantage over biological tests in that the results were clearer, i.e., homozygote/heterozygote presence of the resistance gene can be detected and heterogeneity in seed lots can be identified readily. Within the UPOV framework for granting of PBR, the markers have the potential to fulfil the requirements needed for implementation in DUS testing of candidate varieties and could complement or may be an alternative to the pathogenesis tests that are carried out at present

First Observation of the Submillimeter Polarization Spectrum in a Translucent Molecular Cloud

Polarized emission from aligned dust is a crucial tool for studies of magnetism in the ISM, but a troublesome contaminant for studies of cosmic microwave background polarization. In each case, an understanding of the significance of the polarization signal requires well-calibrated physical models of dust grains. Despite decades of progress in theory and observation, polarized dust models remain largely underconstrained. During its 2012 flight, the balloon-borne telescope BLASTPol obtained simultaneous broadband polarimetric maps of a translucent molecular cloud at 250, 350, and 500 μm. Combining these data with polarimetry from the Planck 850 μm band, we have produced a submillimeter polarization spectrum, the first for a cloud of this type. We find the polarization degree to be largely constant across the four bands. This result introduces a new observable with the potential to place strong empirical constraints on ISM dust polarization models in a previously inaccessible density regime. Compared to models by Draine & Fraisse, our result disfavors two of their models for which all polarization arises due only to aligned silicate grains. By creating simple models for polarized emission in a translucent cloud, we verify that extinction within the cloud should have only a small effect on the polarization spectrum shape, compared to the diffuse ISM. Thus, we expect the measured polarization spectrum to be a valid check on diffuse ISM dust models. The general flatness of the observed polarization spectrum suggests a challenge to models where temperature and alignment degree are strongly correlated across major dust components

ETUDE IN VIVO DES RELATIONS NEURONES-GLIE ET DES FONCTIONS OLIGODENDROCYTAIRES DANS LE SYSTEME NERVEUX CENTRAL DE LA SOURIS GRACE A UN MODELE INDUCTIBLE DE DYSMYELINISATION

LES OLIGODENDROCYTES REPRESENTENT POUR LE SYSTEME NERVEUX CENTRAL DES VERTEBRES UN AVANTAGE FONDAMENTAL ACQUIS AU COURS DE L'EVOLUTION. EN EFFET, CETTE CELLULE GLIALE A LA FORMIDABLE CAPACITE DE FORMER UNE GAINE DE MYELINE AUTOUR DE NOMBREUX AXONES A LA FOIS PERMETTANT AINSI UN GAIN D'ESPACE ET D'ENERGIE ENORME. CETTE GAINE DE MYELINE REPRESENTE ELLE-MEME UN ORGANITE REVOLUTIONNAIRE. ELLE PERMET D'AUGMENTER LA VITESSE DE PROPAGATION DE L'INFLUX NERVEUX PAR LE PHENOMENE DE CONDUCTION SALTATOIRE ISSU DES PROPRIETES ISOLANTES DE LA MYELINE ET DE LA CONCENTRATION DES CANAUX IONIQUES AU NIVEAU DES NUDS DE RANVIER. LA COMPREHENSION DU DEVELOPPEMENT DES OLIGODENDROCYTES DANS LE SYSTEME NERVEUX CENTRAL REPRESENTE UN VASTE DOMAINE D'ETUDES DONT LES RETOMBEES SONT DIRECTEMENT ASSOCIEES A LA RECHERCHE DE THERAPIES POUR DE GRAVES MALADIES HUMAINES COMME LA SCLEROSE EN PLAQUES. IL APPARAIT DE PLUS EN PLUS CLAIREMENT QUE LES OLIGODENDROCYTES SOIENT IMPLIQUES DANS D'AUTRES FONCTIONS QUE LA TRANSMISSION DU MESSAGE NERVEUX. DANS LE BUT D'ETABLIR L'IMPORTANCE DES OLIGODENDROCYTES DANS LE DEVELOPPEMENT DU SYSTEME NERVEUX CENTRAL, NOUS AVONS CREE DANS LE LABORATOIRE PAR LA TECHNIQUE DE TRANSGENESE UN NOUVEAU MODELE ANIMAL : LES SOURIS MBP-TK. GRACE AU SYSTEME D'ABLATION CELLULAIRE APPELLE OBLITERATION PAR LA THYMIDINE KINASE, NOUS AVONS PU INDUIRE SPECIFIQUEMENT LA MORT DES PRECURSEURS DES OLIGODENDROCYTES EN DIVISION. CETTE METHODE NOUS A D'ABORD PERMIS D'ANALYSER LA GENERATION DES OLIGODENDROCYTES AU COURS DU DEVELOPPEMENT POST-NATAL DU CERVEAU. L'UTILISATION DE CE MODELE ANIMAL NOUS A ENSUITE DONNE L'OCCASION D'ETUDIER IN VIVO LE ROLE DE L'OLIGODENDROCYTE DANS LA DISTRIBUTION DE PROTEINES AXONALES DANS LA REGION DU NUD DE RANVIER. ENFIN, NOUS AVONS PU METTRE EN EVIDENCE L'IMPLICATION DES OLIGODENDROCYTES DANS LE DEVELOPPEMENT POST-NATAL DU CERVELET.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF