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Protein S-palmitoylation is increasingly recognized as an important posttranslational modification, present in all eukaryotic organisms, involved in the regulation of many biological processes. The SwissPalm database centralizes the large and increasing number of published palmitoyl-proteome datasets, provides tools to compare them, and includes curated data from the literature on the identification and analysis of palmitoylated proteins. SwissPalm 2 provides an updated version, with 38 palmitoyl-proteomes at the time of release, from 17 different species, and new features such as the inclusion of orthologs.

Protein S-palmitoylation is increasingly recognized as an important posttranslational modification, present in all eukaryotic organisms, involved in the regulation of many biological processes. The SwissPalm database centralizes the large and increasing number of published palmitoyl-proteome datasets, provides tools to compare them, and includes curated data from the literature on the identification and analysis of palmitoylated proteins. SwissPalm 2 provides an updated version, with 38 palmitoyl-proteomes at the time of release, from 17 different species, and new features such as the inclusion of orthologs.

S-Palmitoylation, the only reversible post-translational lipid modification, confers unique biochemical and functional properties to proteins. Although it has long been known that viral proteins are palmitoylated, recent studies reveal that this modification plays a critical role for pathogens of all kinds and at multiple steps of their life cycle. The present review examines the involvement of S-palmitoylation in infection by viruses, bacteria and parasites and illustrates how pathogens have evolved to manipulate the host palmitoylation machinery.

Dans la region semi-aride du Norte Chico (Chili), la variabilite climatique induit une grande variabilite des ressources hydriques superficielles et souterraines. En prenant pour exemple le bassin amont de l’Elqui, nous montrons que, durant les evenements LNSO, les valeurs elevees du coefficient d’ecoulement s’expliquent par une contribution des eaux souterraines aux ecoulements de surface ; durant les annees ENSO, les valeurs plus faibles du coefficient d’ecoulement et la dynamique des variations piezometrique indiquent une recharge importante du compartiment souterrain. Sur la periode 1977–2008 trois dynamiques d’interaction entre compartiments souterrains et superficiels sont identifiees durant les annees hydrologiques caracterisees par un indice pluviometrique eleve : (i) l’augmentation logarithmique du niveau piezometrique, qui illustre une recharge rapide qui s’attenue ensuite, precede celle du debit du cours d’eau ; (ii) l’augmentation exponentielle du niveau piezometrique, qui montre une intensification progressive de la recharge en fonction du temps, succede a celle du debit ; (iii) l’augmentation du niveau piezometrique et du debit sont concomitants. Les dynamiques (i) et (ii) sont observees pendant des evenements ENSO, quand les precipitations sont distribuees sur de larges periodes ; les dynamiques (iii) sont observees pendant des annees neutres, quand les precipitations de forte intensite surviennent sur une periode de temps tres courte. L’analyse de ces dynamiques et des coefficients d’ecoulement montre que lorsque les precipitations moyennes annuelles sont inferieures a 70 mm, l’equilibre relatif entre recharge du compartiment souterrain et ruissellement est rompu, ce qui peut engendrer de forts stress hydriques ; ce seuil pourrait etre utilise en tant qu’indicateur. Enfin, la variabilite spatiale des coefficients d’ecoulement met en evidence une plus grande contribution du compartiment souterrain dans les bassins a forte composante granitique, ce qui semble indiquer une recharge en pied de versant depuis l’horizon alteritique developpe dans les granites.

La plupart des éoliennes offshore sont fondées sur monopieux. L’augmentation constante de la capacité des turbines et l’insuffisance des procédures évoquées dans les documents normatifs, notamment en ce qui concerne la prise en compte des chargements cycliques, posent des défis pour leur dimensionnement. Dans le cas des sites français, la présence de sols et roches carbonatés, dont le comportement est encore mal connu aujourd’hui, rend la tâche encore plus complexe. Le projet SOLCYP+, lancé en 2017 pour une durée de 3 ans, doit permettre de disposer de nouvelles méthodologies fiables et robustes pour le dimensionnement des monopieux de grand diamètre y compris dans le contexte géotechnique du plateau continental français. Cet article présente une description détaillée du projet ANR SOLCYP+. On aborde, tout d’abord, le contexte, la problématique et les objectifs du projet puis, dans un second temps, on décrit plus en détail les quatre principales tâches scientifiques.

We report a very rare case of renal lymphangiectasia, an accumulation of lymph in the renal lymphatic system secondary to obstruction. Our patient presented to his family doctor for an annual check-up which resulted with high blood pressure and polycythemia. An ultrasound was performed and revealed a large right perirenal collection. A year later, a controlled abdominal computed tomography scan showed a progression and compression of perirenal collection on the right kidney, as well as apparition of a left perirenal collection. Percutaneous drainage of both collections was unsuccessful. Laparoscopy-guided marsupialisation was performed and successful. Blood pressure lowered to normal range without medication. The patient’s hemoglobin level decreased within normal range after 3 additional phlebotomies postoperatively.

International audience; In order to guarantee security properties, such as confidentiality and integrity, cryptographic mechanisms provide encryption and signature of data, but protection is required to control the data accesses. The recent attacks on Facebook and Twitter show that the protection must not be limited to the infrastructure i.e. the hosts and the guest virtual machines.

S-palmitoylation involves the attachment of a 16-carbon long fatty acid chain to the cysteine residues of proteins. The process is enzymatic and dynamic with DHHC enzymes mediating palmitoylation and acyl-protein thioesterases reverting the reaction. Proteins that undergo this modification span almost all cellular functions. While the increase in hydrophobicity generated by palmitoylation has the obvious consequence of triggering membrane association, the effects on transmembrane proteins are less intuitive and span a vast range. We review here the current knowledge on palmitoylating and depalmitoylating enzymes, the methods that allow the study of this lipid modification and which drugs can affect it, and finally we focus on four cellular processes for which recent studies reveal an involvement of palmitoylation: endocytosis, reproduction and cell growth, fat and sugar homeostasis and signal transduction at the synapse. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Summary Recent studies suggest that the sterol metabolic network participates in the interferon (IFN) antiviral response. However, the molecular mechanisms linking IFN with the sterol network and the identity of sterol mediators remain unknown. Here we report a cellular antiviral role for macrophage production of 25-hydroxycholesterol (cholest-5-en-3β,25-diol, 25HC) as a component of the sterol metabolic network linked to the IFN response via Stat1. By utilizing quantitative metabolome profiling of all naturally occurring oxysterols upon infection or IFN-stimulation, we reveal 25HC as the only macrophage-synthesized and -secreted oxysterol. We show that 25HC can act at multiple levels as a potent paracrine inhibitor of viral infection for a broad range of viruses. We also demonstrate, using transcriptional regulatory-network analyses, genetic interventions and chromatin immunoprecipitation experiments that Stat1 directly coupled Ch25h regulation to IFN in macrophages. Our studies describe a physiological role for 25HC as a sterol-lipid effector of an innate immune pathway., Graphical Abstract Highlights ► Macrophage PRR sensing of virus or IFN activation induce 25HC synthesis and secretion ► Stat1 rapidly binds and activates the promoter of cholesterol-25-hydroxylase (Ch25h) ► 25HC exerts multilevel antiviral function for a range of different viruses ► 25HC is an intrinsic paracrine and autocrine effector of the IFN antiviral response

International audience; Modern operating systems continue to be the victims of attacks and information leaks. Emerging architectures such as cloud computing or HPC are complex to set up and face many kinds of security threats. However, they still rely on traditional access control mechanisms to protect the system and users' data, whereas these mechanisms can be misconfigured and easily defeated. In this article, we present a full architecture to enhance the protection of H P C clusters. It provides three levels of access control in order to allow the users control over their files while enforcing advanced security properties. More specifically, the integration of mandatory access control enables to control direct information flows, and a new and specific reference monitor deals with indirect information flows. In order to keep a low impact on operating system performances, we propose to centralize this second reference monitor on a dedicated node, controlling the flows on all other nodes through the low latency network. We present the whole architecture and the results of several benchmarks that indicate a low impact on performances. Then we expose how we make this architecture fault-tolerant. This study takes advantage of previous works dealing with access control on workstations or virtualisation technologies, and extends the concepts to the HPC environment.

S-palmitoylation is post-translational modification, which consists in the addition of a C16 acyl chain to cytosolic cysteines and which is unique amongst lipid modifications in that it is reversible. It can thus, like phosphorylation or ubiquitination, act as a switch. While palmitoylation of soluble proteins allows them to interact with membranes, the consequences of palmitoylation for transmembrane proteins are more enigmatic. We briefly review the current knowledge regarding the enzymes responsible for palmitate addition and removal. We then describe various observed consequences of membrane protein palmitoylation. We propose that the direct effects of palmitoylation on transmembrane proteins, however, might be limited to four non-mutually exclusive mechanistic consequences: alterations in the conformation of transmembrane domains, association with specific membrane domains, controlled interactions with other proteins and controlled interplay with other post-translational modifications.

International audience; Assessing the impact of Mandatory Access Control (MAC) integration on the Linux kernel performance is still an open problem. Regarding the specific paradigm of MAC in High Performance Computing, there are actually few works. Yet, guaranteeing security properties on a shared cluster is both a necessity and a challenge. This is a necessity because it is mandatory to ensure the confidentiality and integrity of data computed by the users, and a challenge because a cluster is a costly resource built with performance in mind. This paper deals with the need to integrate MAC in Linux-based operating systems for HPC clusters in an efficient way.

The cholesterol biosynthesis pathway has recently been shown to play an important role in the innate immune response to viral infection with host protection occurring through a coordinate down regulation of the enzymes catalysing each metabolic step. In contrast, statin based drugs, which form the principle pharmaceutical agents for decreasing the activity of this pathway, target a single enzyme. Here, we build an ordinary differential equation model of the cholesterol biosynthesis pathway in order to investigate how the two regulatory strategies impact upon the behaviour of the pathway. We employ a modest set of assumptions: that the pathway operates away from saturation, that each metabolite is involved in multiple cellular interactions and that mRNA levels reflect enzyme concentrations. Using data taken from primary bone marrow derived macrophage cells infected with murine cytomegalovirus or treated with IFNγ, we show that, under these assumptions, coordinate down-regulation of enzyme activity imparts a graduated reduction in flux along the pathway. In contrast, modelling a statin-like treatment that achieves the same degree of down-regulation in cholesterol production, we show that this delivers a step change in flux along the pathway. The graduated reduction mediated by physiological coordinate regulation of multiple enzymes supports a mechanism that allows a greater level of specificity, altering cholesterol levels with less impact upon interactions branching from the pathway, than pharmacological step reductions. We argue that coordinate regulation is likely to show a long-term evolutionary advantage over single enzyme regulation. Finally, the results from our models have implications for future pharmaceutical therapies intended to target cholesterol production with greater specificity and fewer off target effects, suggesting that this can be achieved by mimicking the coordinated down-regulation observed in immunological responses., Graphical abstract Highlights ► We model the cholesterol biosynthesis pathway and its regulation. ► The innate immune response leads to a suppression of flux through the pathway. ► Statin inhibitors show a different mode of suppression to the immune response. ► Statin inhibitor suppression is less robust and less specific than immune suppression.

Cholesterol biosynthesis serves as a central metabolic hub for numerous biological processes in health and disease. An integrative knowledge representation of how the cholesterol pathway is structured and how it interacts with other pathway systems is lacking. Here we provide using Systems Biology Graphical Notation the research synthesis of a process diagram integrating the regulatory and feedback systems for cholesterol synthesis.

Activated macrophages play a central role in controlling inflammatory responses to infection and are tightly regulated to rapidly mount responses to infectious challenge. Type I interferon (alpha/beta interferon [IFN-α/β]) and type II interferon (IFN-γ) play a crucial role in activating macrophages and subsequently restricting viral infections. Both types of IFNs signal through related but distinct signaling pathways, inducing a vast number of interferon-stimulated genes that are overlapping but distinguishable. The exact mechanism by which IFNs, particularly IFN-γ, inhibit DNA viruses such as cytomegalovirus (CMV) is still not fully understood. Here, we investigate the antiviral state developed in macrophages upon reversible inhibition of murine CMV by IFN-γ. On the basis of molecular profiling of the reversible inhibition, we identify a significant contribution of a restricted type I IFN subnetwork linked with IFN-γ activation. Genetic knockout of the type I-signaling pathway, in the context of IFN-γ stimulation, revealed an essential requirement for a primed type I-signaling process in developing a full refractory state in macrophages. A minimal transient induction of IFN-β upon macrophage activation with IFN-γ is also detectable. In dose and kinetic viral replication inhibition experiments with IFN-γ, the establishment of an antiviral effect is demonstrated to occur within the first hours of infection. We show that the inhibitory mechanisms at these very early times involve a blockade of the viral major immediate-early promoter activity. Altogether our results show that a primed type I IFN subnetwork contributes to an immediate-early antiviral state induced by type II IFN activation of macrophages, with a potential further amplification loop contributed by transient induction of IFN-β.

International audience; This paper focuses on the enforcement of security properties fitting with dynamic mandatory access control policies. It adds complementary results to previous works of the authors in order to better address dynamic policies. Previous works of the authors provide several advances for enforcing the security of MAC system.An administration language for formalizing a large set of security properties is available to system administrators. That language uses several flow operators and ease the formalization of the required security properties. A solution is also available for computing the possible violations of any security property that can be formalized using our language. That solution computes several flow graphs in order to find all the allowed activities that can violate the requested properties. That paper addresses remaining problems related to the enforcement of the same kind of properties but with dynamic MAC policies. Enforcement is more much complex if we consider dynamic policies since the states of those policies are theoretically infinite. A new approach is proposed for dynamic MAC policies. The major idea is to use a meta-policy language for controlling the allowed evolutions of those dynamic policies. According to those meta-policy constraints, the computation problem becomes easier. The proposed solution adds meta-nodes within the considered flow graphs. A general algorithm is given for computing the required meta-nodes and the associated arcs. The proposed meta-graphs provide an overestimation of the possible flows between the different meta-nodes. The computation of the possible violations within the allowed dynamic policies is thus allowed. Several concrete security properties are considered using regular expressions for identifying the requested meta-contexts. The resulting violations, within the allowed meta-graphs, are computed and real violations are presented.

International audience; This paper proposes a technical solution for protecting users using a shared NFS service possibly controlled by a malicious user. The main goal is to protect the integrity and confidentiality of user's resources. Moreover, we propose to solve a more difficult challenge: how to prevent a malicious user from exploiting a supposed NFS vulnerability in order to read or write the resources of another user? Thus, this paper assumes that a vulnerability might exist in the NFS protocol or software components that gives the ability to a malicious user to execute any arbitrary code on the NFS server. Technical details about the implantation of Mandatory Access Control mechanisms with Multi Categories on the server side are given. The proposed solution avoids heavy modifications of the clients and only relies on the authentication of these clients.

Ocean colour monitoring is usually based on optical remote sensing with spatial resolutions around 1 km. This spatial scale is available with such sensors as NOAA-AVHRR,POLDER or SeaWiFS, which cover one to several thousand kilometers in a single swath and providing very short revisit periods. The MeRIS sensor, launched on board ENVISAT in 2002, was designed for sea colour observation, with a 300 meter spatial resolution, 15 programmable spectral bands and a 3 day revisit period. Tree hundred meter is a high resolution for an oceanographic sensors, but it is still too rough for coastal water monitoring, where physical and biological phenomena require better spatial resolution [1]. On the opposite, multispectral Landsat ETM images offer a suitable spatial resolution, but have only 4 spectral bands in the visible and near infrared spectrum, allowing poor spectral characterization. A few years ago, in order to combine the spectral resolution of MeRIS and the spatial resolution of Landsat ETM,we had implemented a merging method proposed by Zhukov et al. [2]. Before the launch of ENVISAT, we applied this method to simulated MeRIS images [3]. MeRIS was launched in March 2002 and has been providing images since June 2002. This method is now applied to real MeRIS images. Two product levels are considered. Level 1b contains radiance measurements at the top of the atmosphere for the calibrated and geocoded fifteen (15) MeRIS bands. Level 2 contains normalized surface reflectance and several geophysical and biophysical parameters such as algal pigment index, suspended sediment,Rayleigh-corrected vegetation indices, aerosol type, cloud albedo. The method was tested for radiance (level lb) and reflectance (level 2) over a coastal area of approximately 30times30 km2 located around the Thau lagoon (southern France).

The Medium Resolution Imaging Spectrometer (MERIS) launched in March 2002 and has been providing images since June 2002. Before its launch, we had implemented a method to improve its resolution by merging its images with Landsat Enhanced Thematic Mapper images in order to preserve the best characteristics of the two images (spatial, spectral, temporal). We now present the results of this method for real MERIS images (level 1b and 2) in a coastal area. The robustness of the method is studied as well as the influence of the delay between the acquisitions of the two images.

This paper presents a novel intrusion detection approach and a new infrastructure to enforce the security policy within a distributed system. The solution guaranties the consistency of the security policy and prevents any accidental or malicious update (of the local policies). The control is carried out locally (in each host) in accordance with a meta-policy that enables a distributed control to update a global security policy while satisfying global security properties. The solution is more robust in terms of fault-tolerance and resists to denial of service attacks since the solutions carries out all the control locally. Two levels of intrusion detection are proposed to guaranty the integrity and the consistency of the distributed policy. The first level (meta-level, or administration level) guarantees that each local policy evolves according to the global security properties. This level detects attacks trying inadequate alterations of the local security policies. The second level corresponds to a classical intrusion detection system. But, it can take advantages of the local policy to detect attacks that violate the security objectives. That second level enables to integrate and to adjust various classical IDS. Our approach enforces the security of large scale systems.