New Potential Model for Molecular Dynamic Simulation of liquid HF. II -Parameter Optimization for Repulsion-Dispersion potential

International audienceIn order to build a complete potential model to perform classical molecular dynamic simulations of liquid HF, a new optimization method is proposed to obtain transferable parameters for repulsion-dispersion potential on the basis of ab initio reference data. This process is decomposed into two steps. The first step, using the force-matching method, consists in exploring the parameter space and selecting a first potential used as a start point for the second step. This last step consists in optimizing the parameters of the selected potential in order to reproduce reference thermodynamic and structural data. The obtained potential correctly reproduces the radial distribution functions and the pressures of HF liquid over a large range of thermodynamic states

Molecular Simulations of Hugoniots of detonation products mixtures at chemical equilibrium: Microscopic calculation of the Chapman-Jouguet State

International audienceIn this work, we used simultaneously the Reaction Ensemble Monte Carlo (ReMC) method and the Adaptive Erpenbeck Equation Of State (AE-EOS) method to directly calculate the thermodynamical and chemical equilibrium of mixtures of detonation products on the Hugoniot curve. The ReMC method (W. R. Smith and B. Triska, J. Chem. Phys. 100, pp 3019-3027 (1994)) allows to reach the chemical equilibrium of a reacting mixture, and the AE-EOS method (J. J. Erpenbeck, Phys. Rev. A, 46, p 6406 (1992)) constrains the system to satisfy the Hugoniot relation. Once the Hugoniot curve of the detonation products mixture is established, the CJ state of the explosive can be determined. Performing a NPT simulation at P(CJ) , T(CJ) , we then calculate the direct thermodynamic properties and the following derivative properties of the system using a fluctuation method: calorific capacities, sound velocity and Gruneisen coefficient. As the composition fluctuates, and the number of particles is not necessarily constant in this ensemble, a fluctuation formula has been developed to take into account the fluctuations of mole number and composition. This type of calculation has been applied to several usual energetic materials: nitromethane, tetranitromethane, hexanitroethane, PETN and RDX

The Greater Phenotypic Homeostasis of the Allopolyploid Coffea arabica Improved the Transcriptional Homeostasis Over that of Both Diploid Parents

Polyploidy impacts the diversity of plant species, giving rise to novel phenotypes and leading to ecological diversification. In order to observe adaptive and evolutionary capacities of polyploids, we compared the growth, primary metabolism and transcriptomic expression level in the leaves of the newly formed allotetraploid Coffea arabica species compared with its two diploid parental species (Coffea eugenioides and Coffea canephora), exposed to four thermal regimes (TRs; 18-14, 23-19, 28-24 and 33-29°C). The growth rate of the allopolyploid C. arabica was similar to that of C. canephora under the hottest TR and that of C. eugenioides under the coldest TR. For metabolite contents measured at the hottest TR, the allopolyploid showed similar behavior to C. canephora, the parent which tolerates higher growth temperatures in the natural environment. However, at the coldest TR, the allopolyploid displayed higher sucrose, raffinose and ABA contents than those of its two parents and similar linolenic acid leaf composition and Chl content to those of C. eugenioides. At the gene expression level, few differences between the allopolyploid and its parents were observed for studied genes linked to photosynthesis, respiration and the circadian clock, whereas genes linked to redox activity showed a greater capacity of the allopolyploid for homeostasis. Finally, we found that the overall transcriptional response to TRs of the allopolyploid was more homeostatic compared with its parents. This better transcriptional homeostasis of the allopolyploid C. arabica afforded a greater phenotypic homeostasis when faced with environments that are unsuited to the diploid parental specie

MADGene: retrieval and processing of gene identifier lists for the analysis of heterogeneous microarray datasets

Summary: MADGene is a software environment comprising a web-based database and a java application. This platform aims at unifying gene identifiers (ids) and performing gene set analysis. MADGene allows the user to perform inter-conversion of clone and gene ids over a large range of nomenclatures relative to 17 species. We propose a set of 23 functions to facilitate the analysis of gene sets and we give two microarray applications to show how MADGene can be used to conduct meta-analyses

Ma Orthologous Genes in Prunus spp. Shed Light on a Noteworthy NBS-LRR Cluster Conferring Differential Resistance to Root-Knot Nematodes

Root-knot nematodes (RKNs) are considerable polyphagous pests that severely challenge plants worldwide and especially perennials. The specific genetic resistance of plants mainly relies on the NBS-LRR genes that are pivotal factors for pathogens control. In Prunus spp., the Ma plum and RMja almond genes possess different spectra for resistance to RKNs. While previous works based on the Ma gene allowed to clone it and to decipher its peculiar TIR-NBS-LRR (TNL) structure, we only knew that the RMja gene mapped on the same chromosome as Ma. We carried out a high-resolution mapping using an almond segregating F2 progeny of 1448 seedlings from resistant (R) and susceptible (S) parental accessions, to locate precisely RMja on the peach genome, the reference sequence for Prunus species. We showed that the RMja gene maps in the Ma resistance cluster and that the Ma ortholog is the best candidate for RMja. This co-localization is a crucial step that opens the way to unravel the molecular determinants involved in the resistance to RKNs. Then we sequenced both almond parental NGS genomes and aligned them onto the RKN susceptible reference peach genome. We produced a BAC library of the R parental accession and, from two overlapping BAC clones, we obtained a 336-kb sequence encompassing the RMja candidate region. Thus, we could benefit from three Ma orthologous regions to investigate their sequence polymorphism, respectively, within plum (complete R spectrum), almond (incomplete R spectrum) and peach (null R spectrum). We showed that the Ma TNL cluster has evolved orthologs with a unique conserved structure comprised of five repeated post-LRR (PL) domains, which contain most polymorphism. In addition to support the Ma and RMja orthologous relationship, our results suggest that the polymorphism contained in the PL sequences might underlie differential resistance interactions with RKNs and an original immune mechanism in woody perennials. Besides, our study illustrates how PL exon duplications and losses shape TNL structure and give rise to atypical PL domain repeats of yet unknown role

The Transcription Factor E4F1 Coordinates CHK1-Dependent Checkpoint and Mitochondrial Functions

Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells

Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder–like Behavior

International audienceBACKGROUND: Heterozygous deletion of the TSHZ3 gene, encoding for the teashirt zinc-finger homeobox family member 3 (TSHZ3) transcription factor that is highly expressed in cortical projection neurons (CPNs), has been linked to an autism spectrum disorder (ASD) syndrome. Similarly, mice with Tshz3 haploinsufficiency show ASD-like behavior, paralleled by molecular changes in CPNs and corticostriatal synaptic dysfunctions. Here, we aimed at gaining more insight into "when" and "where" TSHZ3 is required for the proper development of the brain, and its deficiency crucial for developing this ASD syndrome. METHODS: We generated and characterized a novel mouse model of conditional Tshz3 deletion, obtained by crossing Tshz3 flox/flox with CaMKIIalpha-Cre mice, in which Tshz3 is deleted in CPNs from postnatal day 2 to 3 onward. We characterized these mice by a multilevel approach combining genetics, cell biology, electrophysiology, behavioral testing, and bioinformatics. RESULTS: These conditional Tshz3 knockout mice exhibit altered cortical expression of more than 1000 genes, w50% of which have their human orthologue involved in ASD, in particular genes encoding for glutamatergic syn-apse components. Consistently, we detected electrophysiological and synaptic changes in CPNs and impaired corticostriatal transmission and plasticity. Furthermore, these mice showed strong ASD-like behavioral deficits. CONCLUSIONS: Our study reveals a crucial postnatal role of TSHZ3 in the development and functioning of the corticostriatal circuitry and provides evidence that dysfunction in these circuits might be determinant for ASD pathogenesis. Our conditional Tshz3 knockout mouse constitutes a novel ASD model, opening the possibility for an early postnatal therapeutic window for the syndrome linked to TSHZ3 haploinsufficiency

Whole blood transcriptome profiles of trypanotolerant and trypanosusceptible cattle highlight a differential modulation of metabolism and immune response during infection by Trypanosoma congolense

Animal African trypanosomosis, caused by blood protozoan parasites transmitted mainly by tsetse flies, represents a major constraint for millions of cattle in sub-Saharan Africa. Exposed cattle include trypanosusceptible indicine breeds, severely affected by the disease, and West African taurine breeds called trypanotolerant owing to their ability to control parasite development, survive and grow in enzootic areas. Until now the genetic basis of trypanotolerance remains unclear. Here, to improve knowledge of the biological processes involved in trypanotolerance versus trypanosusceptibility, we identified bovine genes differentially expressed in five West African cattle breeds during an experimental infection by Trypanosoma congolense and their biological functions. To this end, whole blood genome-wide transcriptome of three trypanotolerant taurine breeds (N’Dama, Lagune and Baoulé), one susceptible zebu (Zebu Fulani) and one African taurine x zebu admixed breed (Borgou) were profiled by RNA sequencing at four time points, one before and three during infection. As expected, infection had a major impact on cattle blood transcriptome regardless of the breed. The functional analysis of differentially expressed genes over time in each breed confirmed an early activation of the innate immune response, followed by an activation of the humoral response and an inhibition of T cell functions at the chronic stage of infection. More importantly, we highlighted overlooked features, such as a strong disturbance in host metabolism and cellular energy production that differentiates trypanotolerant and trypanosusceptible breeds. N’Dama breed showed the earliest regulation of immune response, associated with a strong activation of cellular energy production, also observed in Lagune, and to a lesser extent in Baoulé. Susceptible Zebu Fulani breed differed from other breeds by the strongest modification in lipid metabolism regulation. Overall, this study provides a better understanding of the biological mechanisms at work during infection, especially concerning the interplay between immunity and metabolism that seems differentially regulated depending on the cattle breeds

Meta-analysis of muscle transcriptome data using the MADMuscle database reveals biologically relevant gene patterns

<p>Abstract</p> <p>Background</p> <p>DNA microarray technology has had a great impact on muscle research and microarray gene expression data has been widely used to identify gene signatures characteristic of the studied conditions. With the rapid accumulation of muscle microarray data, it is of great interest to understand how to compare and combine data across multiple studies. Meta-analysis of transcriptome data is a valuable method to achieve it. It enables to highlight conserved gene signatures between multiple independent studies. However, using it is made difficult by the diversity of the available data: different microarray platforms, different gene nomenclature, different species studied, etc.</p> <p>Description</p> <p>We have developed a system tool dedicated to muscle transcriptome data. This system comprises a collection of microarray data as well as a query tool. This latter allows the user to extract similar clusters of co-expressed genes from the database, using an input gene list. Common and relevant gene signatures can thus be searched more easily. The dedicated database consists in a large compendium of public data (more than 500 data sets) related to muscle (skeletal and heart). These studies included seven different animal species from invertebrates (<it>Drosophila melanogaster, Caenorhabditis elegans</it>) and vertebrates (<it>Homo sapiens, Mus musculus, Rattus norvegicus, Canis familiaris, Gallus gallus</it>). After a renormalization step, clusters of co-expressed genes were identified in each dataset. The lists of co-expressed genes were annotated using a unified re-annotation procedure. These gene lists were compared to find significant overlaps between studies.</p> <p>Conclusions</p> <p>Applied to this large compendium of data sets, meta-analyses demonstrated that conserved patterns between species could be identified. Focusing on a specific pathology (Duchenne Muscular Dystrophy) we validated results across independent studies and revealed robust biomarkers and new pathways of interest. The meta-analyses performed with MADMuscle show the usefulness of this approach. Our method can be applied to all public transcriptome data.</p