In Silico Survey of the Mitochondrial Protein Uptake and Maturation Systems in the Brown Alga Ectocarpus siliculosus

The acquisition of mitochondria was a key event in eukaryote evolution. The aim of this study was to identify homologues of the components of the mitochondrial protein import machinery in the brown alga Ectocarpus and to use this information to investigate the evolutionary history of this fundamental cellular process. Detailed searches were carried out both for components of the protein import system and for related peptidases. Comparative and phylogenetic analyses were used to investigate the evolution of mitochondrial proteins during eukaryote diversification. Key observations include phylogenetic evidence for very ancient origins for many protein import components (Tim21, Tim50, for example) and indications of differences between the outer membrane receptors that recognize the mitochondrial targeting signals, suggesting replacement, rearrangement and/or emergence of new components across the major eukaryotic lineages. Overall, the mitochondrial protein import components analysed in this study confirmed a high level of conservation during evolution, indicating that most are derived from very ancient, ancestral proteins. Several of the protein import components identified in Ectocarpus, such as Tim21, Tim50 and metaxin, have also been found in other stramenopiles and this study suggests an early origin during the evolution of the eukaryotes

Genetics of venous thrombosis: insights from a new genome wide association study

Background: Venous Thrombosis (VT) is a common multifactorial disease associated with a major public health burden. Genetics factors are known to contribute to the susceptibility of the disease but how many genes are involved and their contribution to VT risk still remain obscure. We aimed to identify genetic variants associated with VT risk. Methodology/Principal Findings: We conducted a genome-wide association study (GWAS) based on 551,141 SNPs genotyped in 1,542 cases and 1,110 controls. Twelve SNPs reached the genome-wide significance level of 2.0×10−8 and encompassed four known VT-associated loci, ABO, F5, F11 and FGG. By means of haplotype analyses, we also provided novel arguments in favor of a role of HIVEP1, PROCR and STAB2, three loci recently hypothesized to participate in the susceptibility to VT. However, no novel VT-associated loci came out of our GWAS. Using a recently proposed statistical methodology, we also showed that common variants could explain about 35% of the genetic variance underlying VT susceptibility among which 3% could be attributable to the main identified VT loci. This analysis additionally suggested that the common variants left to be identified are not uniformly distributed across the genome and that chromosome 20, itself, could contribute to ∼7% of the total genetic variance. Conclusions/Significance: This study might also provide a valuable source of information to expand our understanding of biological mechanisms regulating quantitative biomarkers for VT

Modane: A Design Support Tool for Numerical Simulation Codes

International audienceThe continual increasing power of supercomputers allows numerical simulation codes to take into account more complex physical phenomena. Therefore, physicists and mathematicians have to implement complex algorithms using cutting edge technologies and integrate them in large simulators. The CEA-DAM has been studying for several years the contribution of UML/MDE technologies in its simulators development cycle. The Modane application is one of the results of this work

Organisation et structure des génomes mitochondriaux des algues brunes Pylaiella littoralis et Laminaria digitata

The mitochondrial genomes of two brown algae have been studied. The 1st is that of Pylaiella littoralis, which is thought to be primitive algae, the 2nd is that of Laminaria digitata, wich is expected to be an evolved alga, with the aim to compare their genomes. The 1st chapter describes the backgroundof the work: the endosymbiotic events that have given rise to mitochondria and plastids; an insight of what are brown algae and of what we know about mitochondria and their genome. The mitochondrial genomes of P. littoralis and L. digitata are circular DNA molecules of 58.507 bp about 36 kbp respectively. That of P. littoralis contains proteobacterial promoter regions and a T7-like RNA polymerase gene, at the same time. This genome also codes for quite a few ribosomal protein genes. One of them, rpl31, was only described in the mitochondrial DNA (mtDNA) of the primitive prostist Reclinomonas americana before. It also codes for group IIA and IIB introns with multidomaine encoded ORFs. The nad11 gene encodes only the 1st domain of the usual protein with the FeS-binding sequences important for the enzyme activity. The other part of the gene is not encoded in the mtDNA of P. littoralis, nor detected in the nuclear DNA. The cox2 gene exhibits an unusual in-frame insertion of 1006 amino acids within the gene, wich is 280 aa long only. P. littoralis mtDNA has conserved more primitive features than those of other eukaryotes, but has evolved beyond the stage represented by that of the protist R. americana. The sequenced part of the mitochondrial genome of L. digitata (60%) is surprisingly similar to that of P. littoralis. Gene order is nearly exactly the same, adn genesequences show very high homology. The main differences are the lack of introns and of the majority of ORFs. We have also made a few limited comparisons using other brown algae, wich could produce good tools for phylogenetic studies of the brown algae lineage, still mainly unraveled.Deux études de génomes mitochondriaux d'algues brunes sont présentées. La 1ère concerne celui d'une algue primitive Pylaiella littoralis. La 2nde est le début de la comparaison avec celui de Laminaria digitata, considérée comme évoluée. Le contexte de ces études est décrit : la 1ère partie traite des endosymbioses ayant conduit aux mitochondries et aux plastes ; une autre concerne la définition des algues brunes et la 3ème traite des mitochondries et de leur génome. L'ADN mitochondrial (ADNmt) de P. littoralis et de L. digitata consiste en molécules circulaires de 58507 pb et de 36k pb, respectivement. Celui de P. littoralis contient à la fois des promoteurs de type eubactérien et un gène d'ARN polymérase de type phagique. Ce génome code plusieurs gènes de protéines ribosomiques, dont rpl31, identifié avant uniquement dans l'ADNmt d'un protiste primitif, Reclinomonas americana. Il code aussi des introns des groupes IIA et IIB, avec des ORFs multidomaines complets. Le gène nad11 ne comporte que le 1er tiers du gène habituel, soit celui des domaines de liaison aux groupements FeS, dont l'importance a été montrée pour l'activité de l'enzyme. L'autre partie n'est pas codée dans l'ADNmt et n'a pas été détectée dans l'ADN nucléaire. Le gène cox2, lui, comporte une insertion de 1006 aa alors qu'il n'en code lui-même que 280. L'ADNmt de P. littoralis a conservé plus de caractères primitifs que ceux des autres eucaryotes tout en ayant plus évolué que celui de R. americana. Les 60% du génome mitochondrial de L. digitata qui sont séquencés ressemblent étonnamment à celui de P. littoralis. L'ordre des gènes est presque identique et leurs séquences ont de très fortes homologies. Les principales différences sont l'absence des introns et la plupart des ORFs. Nous avons aussi fait plusieurs comparaisons ponctuelles avec d'autres algues brunes qui pourraient être un outil utile dans l'étude des relations phylogénétiques de la lignée des algues brunes, encore peu connue

Applying Model-Driven Engineering to High-Performance Computing: Experience Report, Lessons Learned, and Remaining Challenges

International audienc

Fostering metamodels and grammars within a dedicated environment for HPC: the NabLab environment (tool demo)

International audienceAdvanced and mature language workbenches have been proposed in the past decades to develop Domain-Specific Languages (DSL) and rich associated environments. They all come in various flavors, mostly depending on the underlying technological space (e.g., grammarware or modelware). However, when the time comes to start a new DSL project, it often comes with the choice of a unique technological space which later bounds the possible expected features. In this tool paper, we introduce NabLab, a full-fledged industrial environment for scientific computing and High Performance Computing (HPC), involving several metamod-els and grammars. Beyond the description of an industrial experience of the development and use of tool-supported DSLs, we report in this paper our lessons learned, and demonstrate the benefits from usefully combining metamodels and grammars in an integrated environment

Practical Runtime Instrumentation of Software Languages: The Case of SciHook

SLE 2023 will be co-located with SPLASH 2023International audienceSoftware languages have pros and cons, and are usually chosen accordingly. In this context, it is common to involve different languages in the development of complex systems, each one specifically tailored for a given concern. However, these languages create de facto silos, and offer little support for interoperability with other languages, be it statically or at runtime. In this paper, we report on our experiment on extracting a relevant behavioral interface from an existing language, and using it to enable interoperability at runtime. In particular, we present a systematic approach to define the behavioral interface and we discuss the expertise required to define it. We illustrate our work on the case study of SciHook, a C++ library enabling the runtime instrumentation of scientific software in Python. We present how the proposed approach, combined with SciHook, enables interoperability between Python and a domain-specific language dedicated to numerical analysis, namely \NabLab, and discuss overhead at runtime

Practical Runtime Instrumentation of Software Languages: The Case of SciHook

SLE 2023 will be co-located with SPLASH 2023International audienceSoftware languages have pros and cons, and are usually chosen accordingly. In this context, it is common to involve different languages in the development of complex systems, each one specifically tailored for a given concern. However, these languages create de facto silos, and offer little support for interoperability with other languages, be it statically or at runtime. In this paper, we report on our experiment on extracting a relevant behavioral interface from an existing language, and using it to enable interoperability at runtime. In particular, we present a systematic approach to define the behavioral interface and we discuss the expertise required to define it. We illustrate our work on the case study of SciHook, a C++ library enabling the runtime instrumentation of scientific software in Python. We present how the proposed approach, combined with SciHook, enables interoperability between Python and a domain-specific language dedicated to numerical analysis, namely \NabLab, and discuss overhead at runtime

Monilogging for Executable Domain-Specific Languages

International audienceRuntime monitoring and logging are fundamental techniques for analyzing and supervising the behavior of computer programs. However, supporting these techniques for a given language induces significant development costs that can hold language engineers back from providing adequate logging and monitoring tooling for new domain-specific modeling languages. Moreover, runtime monitoring and logging are generally considered as two different techniques: they are thus implemented separately which makes users prone to overlooking their potentially beneficial mutual interactions. We propose a language-agnostic, unifying framework for runtime monitoring and logging and demonstrate how it can be used to define loggers, runtime monitors and combinations of the two, aka. moniloggers. We provide an implementation of the framework that can be used with Java-based executable languages, and evaluate it on 2 implementations of the NabLab interpreter, leveraging in turn the instrumentation facilities offered by Truffle, and those offered by AspectJ