Vulnerability assessment of distributed systems

In this project I have carried out a vulnerability assessment of a component of the Condor Middleware. In this assessment I have sought and found the more dangerous software vulnerabilities of this system, I have reported them to the development team such that they may be fixed, and thus improve the security of this distributed system, and the networks that use it.En este proyecto he desarrollado una evaluación de vulnerabilidades de un componente del Middleware Condor. En esta evaluación he buscado y encontrado las vulnerabilidades más peligrosas de este sistema, las he reportado al equipo de desarrolladores para ser arregladas, y mejorar así la seguridad este sistema distribuido y de las redes que lo utilizan.En aquest projecte he desenvolupat una avaluació de vulnerabilitats d'un components del Middleware Condor. En aquesta avaluació he buscat i trobat les vulnerabilitats més perilloses d'aquest sistema, les he reportat a l'equip de desenvolupadors per a ser arreglades, i millorar així la seguretat d'aquest sistema distribuït i de les xarxes que el fan servir

Earliest holozoan expansion of phosphotyrosine signaling

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Phosphotyrosine (pTyr) signaling is involved in development and maintenance of metazoans' multicellular body through cell-to-cell communication. Tyrosine kinases (TKs), tyrosine phosphatases, and other proteins relaying the signal compose the cascade. Domain architectures of the pTyr signaling proteins are diverse in metazoans, reflecting their complex intercellular communication. Previous studies had shown that the metazoan-type TKs, as well as other pTyr signaling proteins, were already diversified in the common ancestor of metazoans, choanoflagellates, and filastereans (which are together included in the clade Holozoa) whereas they are absent in fungi and other nonholozoan lineages. However, the earliest-branching holozoans Ichthyosporea and Corallochytrea, as well as the two fungi-related amoebae Fonticula and Nuclearia, have not been studied. Here, we analyze the complete genome sequences of two ichthyosporeans and Fonticula, and RNAseq data of three additional ichthyosporeans, one corallochytrean, and Nuclearia. Both the ichthyosporean and corallochytrean genomes encode a large variety of receptor TKs (RTKs) and cytoplasmic TKs (CTKs), as well as other pTyr signaling components showing highly complex domain architectures. However, Nuclearia and Fonticula have no TK, and show much less diversity in other pTyr signaling components. The CTK repertoires of both Ichthyosporea and Corallochytrea are similar to those of Metazoa, Choanoflagellida, and Filasterea, but the RTK sets are totally different from each other. The complex pTyr signaling equipped with positive/negative feedback mechanism likely emerged already at an early stage of holozoan evolution, yet keeping a high evolutionary plasticity in extracellular signal reception until the co-option of the system for cell-to-cell communication in metazoans. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.This work was supported by the European Research Council Starting grant ERC-2007-StG-206883 to I.R.-T; Ministerio de Ciencia e Innovación grant BFU2008-02839/BMC to I.R.-T.; and the Marie Curie Intra-European Fellowship (MMEMA) within the 7th European Community Framework Programme to H.S.Peer Reviewe

Parvularia atlantis gen. et sp. nov., a Nucleariid Filose Amoeba (Holomycota, Opisthokonta)

International audienceThe opisthokonts constitute a eukaryotic supergroup divided into two main clades: the holozoans, which include animals and their unicellular relatives, and the holomycotans, which include fungi, opisthosporidians and nucleariids. Nucleariids are phagotrophic filose amoebae that phenotypically resemble more their distant holozoan cousins than their holomycotan phylogenetic relatives. Despite their evolutionary interest, the diversity and internal phylogenetic relationships within the nucleariids remain poorly studied. Here we formally describe and characterize by molecular phylogeny and microscopy observations Parvularia atlantis gen. et sp. nov. (formerly Nuclearia sp. ATCC 50694), and compare its features with those of other nucleariid genera. Parvularia is an amoebal genus characterized by radiating knobbed and branching filopodia. It exhibits prominent vacuoles observable under light microscopy, a cyst-like stage, and completely lacks cilia. P. atlantis possesses one or two nuclei with a central nucleolus, and mitochondria with flat or discoid cristae. These morphological features, although typical of nucleariids, represent a combination of characters different to those of any other described Nuclearia species. Likewise, 18S rRNA-based phylogenetic analyses show that P. atlantis represents a distinct lineage within the nucleariids. Keywords Protist evolution; nucleariid amoeba; protist diversity; filosea; taxonomy; phylogeny FROM a taxonomic point of view, Opisthokonta is considered one of the largest eukaryotic supergroups (Adl et al. 2012). It is divided into two clades: the Holozoa, which contains animals and their unicellular relatives (Lang et al. 2002), and the Holomycota (Liu et al

The Capsaspora genome reveals a complex unicellular prehistory of animals

Suga, Hiroshi et al.-- This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.To reconstruct the evolutionary origin of multicellular animals from their unicellular ancestors, the genome sequences of diverse unicellular relatives are essential. However, only the genome of the choanoflagellate Monosiga brevicollis has been reported to date. Here we completely sequence the genome of the filasterean Capsaspora owczarzaki, the closest known unicellular relative of metazoans besides choanoflagellates. Analyses of this genome alter our understanding of the molecular complexity of metazoans' unicellular ancestors showing that they had a richer repertoire of proteins involved in cell adhesion and transcriptional regulation than previously inferred only with the choanoflagellate genome. Some of these proteins were secondarily lost in choanoflagellates. In contrast, most intercellular signalling systems controlling development evolved later concomitant with the emergence of the first metazoans. We propose that the acquisition of these metazoan-specific developmental systems and the co-option of pre-existing genes drove the evolutionary transition from unicellular protists to metazoans. © 2013 Macmillan Publishers Limited. All rights reserved.H.S. was supported by the Marie Curie Intra-European Fellowship within the 7th European Community Framework Programme. Genome sequencing, assembly and some supporting analysis was supported by grants from the National Human Genome Research Institute (HG003067-05 through HG003067-10), as were C.N., C.R., B.H. and Z.C. B.F.L. and A.J.R. acknowledge financial support through the Canadian Research Chair program. This study was supported by an ICREA contract, a European Research Council Starting Grant (ERC-2007-StG-206883) and a grant (BFU2011-23434) from the Spanish Ministry of the Economy and Competitiveness (MINECO) awarded to I.R.-T. M.V. was supported by CNRS, the Agence Nationale de la Recherche (ANR grant BLAN-0294) and the Institut Universitaire de France.Peer Reviewe

Automating risk analysis of software design models

The growth of the internet and networked systems has exposed software to an increased amount of security threats. One of the responses from software developers to these threats is the introduction of security activities in the software development lifecycle. This paper describes an approach to reduce the need for costly human expertise to perform risk analysis in software, which is common in secure development methodologies, by automating threat modeling. Reducing the dependency on security experts aims at reducing the cost of secure development by allowing non-security-aware developers to apply secure development with little to no additional cost,making secure development more accessible. To automate threat modeling two data structures are introduced, identification trees and mitigation trees, to identify threats in software designs and advise mitigation techniques, while taking into account specification requirements and cost concerns. These are the components of our model for automated threat modeling, AutSEC.We validated AutSEC by implementing it in a tool based on data flow diagrams, from theMicrosoft security development methodology, and applying it to VOMS, a grid middleware component, to evaluate our model's performance

A phylogenetic and proteomic reconstruction of eukaryotic chromatin evolution

Histones and associated chromatin proteins have essential functions in eukaryotic genome organization and regulation. Despite this fundamental role in eukaryotic cell biology, we lack a phylogenetically comprehensive understanding of chromatin evolution. Here, we combine comparative proteomics and genomics analysis of chromatin in eukaryotes and archaea. Proteomics uncovers the existence of histone post-translational modifications in archaea. However, archaeal histone modifications are scarce, in contrast with the highly conserved and abundant marks we identify across eukaryotes. Phylogenetic analysis reveals that chromatin-associated catalytic functions (for example, methyltransferases) have pre-eukaryotic origins, whereas histone mark readers and chaperones are eukaryotic innovations. We show that further chromatin evolution is characterized by expansion of readers, including capture by transposable elements and viruses. Overall, our study infers detailed evolutionary history of eukaryotic chromatin: from its archaeal roots, through the emergence of nucleosome-based regulation in the eukaryotic ancestor, to the diversification of chromatin regulators and their hijacking by genomic parasites.Research in the A.S.-P. group was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 851647) and the Spanish Ministry of Science and Innovation (PGC2018-098210-A-I00). We also acknowledge support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme (Generalitat de Catalunya). C.N. is supported by an FPI PhD fellowship from the Spanish Ministry of Economy, Industry and Competitiveness (MEIC). X.G.-B. is supported by a Juan de la Cierva fellowship (FJC2018-036282-I) from MEIC. I.R.-T. was supported by a European Research Council (grant no. 616960). B.F.L. was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC; RGPIN-2017-05411) and by the ‘Fonds de Recherche Nature et Technologie’, Quebec. P.L.-G. and D.M. were supported by a Moore and Simons foundations grant (GBMF9739) and by European Research Council advanced grants (322669, 787904). Research in the C.S. group was supported by the ERC through project TACKLE (advanced grant no. 695192)

Molekulare Mechanismen im Prozess der Zellreprogrammierung

Die bahnbrechende Entdeckung, dass somatische Zellen einen stabilen pluripotenten Zustand durch die ektopische Expression von spezifischen Transkriptionsfaktoren annehmen können, hat die Möglichkeiten der regenerativen Medizin wesentlich erweitert. Induzierte pluripotente Stammzellen (iPS) haben sich zu einem außerordentlich wertvollen Instrument entwickelt, um patientenspezifische Therapien zu ermöglichen. Obwohl große technologische Fortschritte in der Verbesserung der Methodik erzielt wurden, sind die zugrundeliegenden molekularen Mechanismen im Prozess der Zellreprogrammierung weitgehend unbekannt. Um die molekularen Mechanismen zu untersuchen, welche die Induktion der Pluripotenz vorantreiben oder verhindern, wurden in dieser Arbeit genomweit Transkriptionsprofile humaner Fibroblasten nach Überexpression der Reprogrammierungsfaktoren, OCT4, SOX2, KLF4 und c-MYC, einzeln und in Kombination untersucht. Die Analyse des Transkriptoms in der frühesten Phase der Reprogrammierung ermöglichte die Identifizierung von Signalwegen, die primär für die Reprogrammierung von somatischen Zellen verantwortlich sind. Diese Signalwege wurden in ein mathematisches Modell integriert, das zur funktionalen Analyse der identifizierten Komponenten und Signalwege genutzt wurde. Dies ermöglichte die Aufstellung von Hypothesen über die der Reprogrammierung zugrundeliegenden molekularen Mechanismen. Die aufgestellten Hypothesen wurden anhand der beiden wichtigsten involvierten Proteine, p53 und TGFβ-Rezeptoren, während des Prozesses der Reprogrammierung überprüft. Dabei wurden p53 genetisch und der TGFβ-Rezeptor pharmakologisch untersucht. Die in dieser Arbeit erzielten Ergebnisse zeigen, dass die beginnende Reprogrammierung somatischer Zellen einen an den embryonalen Zellzyklus angelehnten Mechanismus verfolgt. Der synergistische Effekt der Reprogrammierungsfaktoren reguliert den TGFβ- und den p53-Signalweg und mindert damit die Anti-Wachstums-Reaktionen, die Hürden für die Reprogrammierung wären. Die Unterdrückung dieser Signalwege schaltet die G1-S Phase Kontrollpunkte aus und ermöglicht so einen den embryonalen Stammzellen ähnlichen Zellzyklus. Schnellere G1-S Übergänge reduzieren die Aktivität des Replikations-Reparaturmechanismus und bevorzugen die homologe Rekombination, welche damit zum dominierenden Reparaturmechanismus in der Zelle wird.The landmark discovery that lineage-restricted cells can acquire a stable pluripotent state through the ectopic expression of a specific set of transcription factors has expanded the boundaries of regenerative medicine to a yet indefinite end. Induced pluripotent stem cells (iPS) have emerged as an invaluable tool for generating patient-specific therapies. Even though, many technical advances have been made to improve the methodology less is known about the molecular mechanisms involved in the process of reprogramming. In order to investigate the molecular mechanisms that promote or hinder the induction of pluripotency I have studied the genome-wide transcriptional profile of human fibroblasts after over-expression of the reprogramming transcription factors (OCT4, SOX2, KLF4, and c-MYC) independently and in combination. The analysis of the transcriptome at the early stages of the reprogramming permitted the identification of the foremost pathways involved in the reprogramming of somatic cells. Moreover, these pathways were given functional meaning by assembling a mathematical model that helped to propose hypotheses about the molecular mechanisms driving the reprogramming process. These hypotheses have been validated in loss of function experiments by targeting genetically or pharmacologically the most relevant proteins involved, as p53 and TGFβ receptor, during the reprogramming process. The data presented in this work demonstrate that the reprogramming of somatic cells begins in the pursuit of a rapid, embryonic-like, cell cycle. The synergistic effect of the reprogramming factors regulates the TGFβ and the p53 signalling pathway reducing their related anti-growth responses, barriers to reprogramming. Regulation of these pathways eliminates the G1-S transition checkpoint promoting a cell cycle progression similar to embryonic stem cells. In addition, I probed that this regulation of the cell cycle has down-stream effects on DNA damage responses and apoptosis. Faster G1-S transitions reduced the activity on replication-related repair mechanisms in favour of homologous recombination that became the most prominent repair mechanism in the cells

Vulnerability assessment of distributed systems

In this project I have carried out a vulnerability assessment of a component of the Condor Middleware. In this assessment I have sought and found the more dangerous software vulnerabilities of this system, I have reported them to the development team such that they may be fixed, and thus improve the security of this distributed system, and the networks that use it.En este proyecto he desarrollado una evaluación de vulnerabilidades de un componente del Middleware Condor. En esta evaluación he buscado y encontrado las vulnerabilidades más peligrosas de este sistema, las he reportado al equipo de desarrolladores para ser arregladas, y mejorar así la seguridad este sistema distribuido y de las redes que lo utilizan.En aquest projecte he desenvolupat una avaluació de vulnerabilitats d'un components del Middleware Condor. En aquesta avaluació he buscat i trobat les vulnerabilitats més perilloses d'aquest sistema, les he reportat a l'equip de desenvolupadors per a ser arreglades, i millorar així la seguretat d'aquest sistema distribuït i de les xarxes que el fan servir

Parvularia gen. nov. represents a filose amoeba related to nucleariids, the earliest-branching lineage of Holomycota (Opisthokonta)

Trabajo presentado en el Moscow Forum PROTIST 2016, celebrado en Moscú del 6 al 10 de junio de 2016.Opisthokonts, one of the largest eukaryotic supergroups, is divided into two major clades: the Holozoa, encompassing animals and their unicellular relatives, and the Holomycota, including fungi and their unicellular relatives. The earliest-branching lineage in Holomycota, which has received many names (e.g. Nucleariidae, Cristidiscoidia, Discicristata), remains poorly studied. This group of phagotrophic filose amoebae bears contrasting features in comparison with those of their close relatives, the parasitic Opisthosporidia and the osmotrophic fungi. It originally contained a single genus, Nuclearia, which includes naked amoebae of ca. 40 μm cell diameter that feed on filamentous cyanobacteria in freshwater environments. More recently, Fonticula alba was included as sister to Nuclearia spp. With much smaller cell size and bacterivore, this amoeba presents an aggregative multicellular fruiting body. Here we describe the new genus Parvularia nov. gen., a small filose amoeba formerly called Nuclearia sp. ATCC50694, and we compare its morphological features with those of the genera Nuclearia and Fonticula. We also review the whole nucleariid lineage at the onset of Holomycota, focusing on their diversity, ecology and evolutionary importance. SSU rRNA-based phylogenetic analyses including environmental sequences suggest that nucleariids are relatively scarce and thrive exclusively in freshwater systems. Based on existing transcriptomic data for Parvularia and novel data for a canonical Nuclearia strain, we carried out phylogenomic analyses to study the internal phylogeny of the whole group. Nucleariids occupy a key evolutionary position, such that mapping phenotypic traits on the phylogeny of Opisthokonts will help understanding important evolutionary transitions such multicellularity, parasitism or osmotrophy.N

Automating risk analysis of software design models

The growth of the internet and networked systems has exposed software to an increased amount of security threats. One of the responses from software developers to these threats is the introduction of security activities in the software development lifecycle. This paper describes an approach to reduce the need for costly human expertise to perform risk analysis in software, which is common in secure development methodologies, by automating threat modeling. Reducing the dependency on security experts aims at reducing the cost of secure development by allowing non-security-aware developers to apply secure development with little to no additional cost,making secure development more accessible. To automate threat modeling two data structures are introduced, identification trees and mitigation trees, to identify threats in software designs and advise mitigation techniques, while taking into account specification requirements and cost concerns. These are the components of our model for automated threat modeling, AutSEC.We validated AutSEC by implementing it in a tool based on data flow diagrams, from theMicrosoft security development methodology, and applying it to VOMS, a grid middleware component, to evaluate our model's performance