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Octopamine (OA) is an important neuroactive substance that modulates several physiological functions and behaviors of various invertebrate species. This biogenic monoamine, structurally related to noradrenaline, acts as a neurotransmitter, a neuromodulator, or a neurohormone in insects. The tyramine β-hydroxylase (TBH) catalyzes the last step in OA biosynthesis and thus plays a key role in the regulation of synthesis and secretion of OA in neurons. The aim of this study was to characterize TBH in the cockroach Periplaneta americana and to get a better understanding of its regulation under stress conditions in this insect. First of all, five full-length cDNAs encoding TBH isoforms were cloned from the nerve cord of the physiological model P. americana. PaTBH transcripts were found mainly expressed in nervous tissues and in octopaminergic dorsal unpaired median neurons. In addition, a new ELISA assay was developed so as to allow determination of both OA level and TBH activity in stressed cockroaches. Mechanical stressful stimulation led to a significant increase in TBH activity after 1 and 24 h, with a higher induction after 1 h than after 24 h. Thus, TBH could be considered as a promising biomarker of stress in insects rather than OA.

International audience; Genetic data are increasingly used in landscape ecology for the indirect assessment of functional connectivity, that is, the permeability of landscape to movements of organ- isms. Among available tools, matrix correlation analyses (e.g. Mantel tests or mixed models) are commonly used to test for the relationship between pairwise genetic dis- tances and movement costs incurred by dispersing individuals. When organisms are spatially clustered, a population-based sampling scheme (PSS) is usually performed, so that a large number of genotypes can be used to compute pairwise genetic distances on the basis of allelic frequencies. Because of financial constraints, this kind of sam- pling scheme implies a drastic reduction in the number of sampled aggregates, thereby reducing sampling coverage at the landscape level. We used matrix correlation analy- ses on simulated and empirical genetic data sets to investigate the efficiency of an individual-based sampling scheme (ISS) in detecting isolation-by-distance and isola- tion-by-barrier patterns. Provided that pseudo-replication issues are taken into account (e.g. through restricted permutations in Mantel tests), we showed that the use of inter- individual measures of genotypic dissimilarity may efficiently replace interpopulation measures of genetic differentiation: the sampling of only three or four individuals per aggregate may be sufficient to efficiently detect specific genetic patterns in most situa- tions. The ISS proved to be a promising methodological alternative to the more con- ventional PSS, offering much flexibility in the spatial design of sampling schemes and ensuring an optimal representativeness of landscape heterogeneity in data, with few aggregates left unsampled. Each strategy offering specific advantages, a combined use of both sampling schemes is discussed.

The syndrome termed 'Drug Reaction with Eosinophilia and Systemic Symptoms' (DRESS) is an unpredictable, life-threatening condition associated with adverse reactions to therapy. Although the etiology of DRESS is poorly understood, genetic susceptibility markers have been identified within the HLA complex and there are several prevailing models of pathogenesis. Modification of host antigens by haptens (drugs or their metabolites), or non-covalent drug binding to endogenous proteins (the p-i concept), may drive pro-inflammatory immune responses in patients. Alternatively, a viral trigger for DRESS has been proposed based on the concomitant detection of herpesviruses and the recent demonstration of Epstein-Barr virus-specific immune responses in DRESS patients. In the present review, we discuss the latest findings concerning the pathogenesis of drug reactions and known risk factors for DRESS.

International audience; OBJECTIVE To identify the prognostic factors of overall survival in a series of patients with paraneoplastic pemphigus (PNP). DESIGN Multicenter retrospective cohort study. SETTING Twenty-seven dermatology departments in France. PATIENTS A total of 53 patients (31 men and 22 women; median age, 59 years; age range, 30-88 years) were diagnosed as having PNP between 1992 and 2010. MAIN OUTCOME MEASURES Overall Kaplan-Meier survival rates were estimated, and features associated with survival were assessed using univariate (log-rank test) and multivariate (Cox regression) analyses. RESULTS The study included 53 patients with PNP. Thirty-six patients (68%) died during the study. The 1-, 3-, and 5-year overall survival rates were 49%, 41%, and 38%, respectively. The main causes of death were infections (n = 21) and evolution of neoplasia (n = 6). In univariate analysis, the main detrimental prognostic factors identified were erythema multiforme-like skin lesions (P = .05) and histologic keratinocyte necrosis (P = .03). None of the 5 patients with Castleman disease died during the study. After adjustment for age and sex in multivariate analysis, erythema multiforme-like skin lesions remained predictive of fatal outcome, with a 2-fold increase in death rate (hazard ratio [HR], 2.3; 95% CI, 1.05-5.03; P = .04). The prognosis of patients with PNP was even poorer when erythema multiforme-like skin lesions were associated with severe skin or mucosal involvement at presentation (HR of death, 3.0; 95% CI, 1.01-8.92; P = .049). CONCLUSION Patients with PNP with erythema multiforme-like skin lesions and histologic keratinocyte necrosis, especially when associated with extensive lesions at presentation, are likely to have a more severe and rapid fatal outcome and should be managed very carefully.

αβ T-cell lines specific for sulfatide, an abundant myelin glycosphingolipid presented by various CD1 molecules, have been previously derived from PBMCs of patients with demyelinating diseases such as multiple sclerosis (MS) but also from healthy subjects. Using an unbiased tetramer-based MACS enrichment method to enrich for rare antigen-specific cells, we confirmed the presence of CD1d-sulfatide-specific T cells in all healthy individuals examined. Surprisingly, the great majority of fresh sulfatide-specific T cells belonged to the γδ lineage. Furthermore, these cells used the Vδ1 TCR variable segment, which is uncommon in the blood but predominates in tissues such as the gut and specifically accumulates in MS lesions. Recombinant Vδ1 TCRs from different individuals were shown to bind recombinant CD1d-sulfatide complexes in a sulfatide-specific manner. These results provide the first direct demonstration of MHC-like-restricted, antigen-specific recognition by γδ TCRs. Together with previous reports, they support the notion that human Vδ1 T cells are enriched in CD1-specific T cells and suggest that the Vδ1 T-cell population that accumulates in MS lesions might be enriched in CD1-sulfatide specific cells.

International audience; This study introduces a novel DNA sampling method in amphibians using skin swabs. We assessed the relevancy of skin swabs relevancy for genetic studies by amplifying a set of 17 microsatellite markers in the alpine newt Ichthyosaura alpestris, including 14 new polymorphic loci, and a set of 11 microsatellite markers in Hyla arborea, from DNA collected with buccal swabs (the standard swab method), dorsal skin swabs and ventral skin swabs. We tested for quality and quantity of collected DNA with each method by comparing electrophoresis migration patterns. The consistency between genotypes obtained from skin swabs and buccal swabs was assessed. Dorsal swabs performed better than ventral swabs in both species, possibly due to differences in skin structure. Skin swabbing proved to be a useful alternative to buccal swabbing for small or vulnerable animals: by drastically limiting handling, this method may improve the trade-off between the scientific value of collected data, individual welfare and species conservation. In addition, the 14 new polymorphic microsatellites for the alpine newt will increase the power of genetic studies in this species. In four populations from France (n = 19-25), the number of alleles per locus varied from 2 to 16 and expected heterozygosities ranged from 0.04 to 0.91. Presence of null alleles was detected in two markers and two pairs displayed gametic disequilibrium. No locus appeared to be sex-linked.

International audience; The problem of physical design automation is a difficult problem due to the huge number of devices, and physical constraints to be met. The Model-Driven Engineering (MDE) approach aims to tackle the complexity of software development using a high level method based on models and transformations. While this approach is used for High-Level circuit synthesis there is no work reported on the lower part of the circuit design automation flow, namely the physical-design automation. In this work, we use the MDE approach to model the physical synthesis process with a focus mainly on reconfigurable architectures. We present a model for island style FPGAs along with the transformations needed in the case of the physical synthesis. The main result of this work is to show the feasibility of the MDE approach for the physical design automation problem, and we argue that this methodology enables orthogonal composition of the architecture / algorithms / application design space, that enables incremental exploration based on quantitative evaluations.

14 pages; International audience; This paper presents a setup for teaching configware to master students. Our approach focuses on experiment and leaning-by- doing while being supported by research activity. The central project we submit to students addresses building up a simple RISC processor, that supports an extensible instructions set thanks to its reconfigurable functional unit. The originality comes from that the students make use of the Biniou framework. Biniou is a research tool which approach covers tasks ranging from describing the RFU, synthesizing it as VHDL code, and implementing applications over it. Once done, students exhibit a deep understanding of the domain, ensuring the ability to fast adapt to state-of-the-art techniques.

International audience; We describe a non-invasive, PCR-RFLP-based method that allows reliable determination of the European water frog species Pelophylax lessonae and Pelophylax ridibundus and the hybrid form Pelophylax esculentus. Maximum-likelihood analysis of ITS2 sequences revealed two robust monophyletic clades corresponding to water frogs of the P. lessonae and P. ridibundus groups. Three restriction enzymes (KpnI, HaeII, and SmaI) were used to digest three conserved ITS2 domains. Taxonomic identification was unambiguous; the three restriction enzymes gave the same results. A French reference sample was identified using allozyme electrophoresis. Our PCR-RFLP method confirmed circa 83% of identification of the allozyme method. We conclude that the difference between identifications was caused by introgression. The western Palearctic water frog (WPWF) group is an impressive example demonstrating the importance of molecular methods for species determination (Hotz 1983; Pagano & Joly 1999; Hotz & Semlitsch 2000; Lodé & Pagano 2000; Plötner & Ohst 2001; Plötner et al. 2001, 2007), for example, in the context of conservation and biodiversity studies. Many WPWF species are morphologically uniform but exhibit specific molecular characters such as unique protein-coding alleles (Plötner & Ohst 2001), microsatellites (Garner et al. 2000; Zeisset & Beebee 2000; Hotz et al. 2001; Christiansen 2005; Holsbeek et al. 2008, 2009a,b), nuclear sequences (Ohst 2008; Plötner et al. 2009), and mitochondrial (mt) DNA markers (Plötner 1998; Holsbeek et al. 2008; Plötner et al. 2008). Widespread hybridization between genetically similar water frog species and lineages (e.g. Akın et al. 2010) may pose serious problems for species determination. In contrast to water frogs from Anatolia and central Asia, the Central and eastern European species Pelophylax lessonae and Pelophylax ridibundus and their hybridogenetic associate Pelophylax esculentus possess distinct morphological and bioacoustic characters that allow an almost exact determination of these forms (Günther 1990; Plötner 2005). Nevertheless, the occurrence of triploid hybrids that possess either two lessonae genomes and one ridibundus genome (LLR) or two ridibundus genomes and one lessonae genome (RRL) hampers identification because of gene-dosage effects (Berger et al. 1986; Vorburger 2001): in LLR individuals, the L genome is expressed twice resulting in a lessonae-like phenotype, while RRL hybrids are often similar to P. ridibundus. In western Europe, the determination of water frogs by morphological and bioacoustic methods may also fail because of extensive hybridization between autochthonous and allochthonous lineages (Günther et al. 1979; Pagano et al. 2003; Christiansen 2005; Holsbeek et al. 2008), which produces intermediate character states for many individuals. Furthermore, character expression depends on age; compared to adults, diagnostic characters are often less clearly expressed in juveniles. Thus, genetic markers are a valuable addition to morphology for identifying adult frogs and even more useful for the determination of juveniles and larvae. Here, we present a relatively inexpensive, rapid, and non-invasive molecular method that allows distinguishing the European water frog forms P. lessonae, P. ridibundus, and P. esculentus with high certainty. Our method is based on specific restriction sites in a 271- bp PCR fragment obtained from the internal transcribed spacer 2 (ITS2) of WPWFs. This ribosomal DNA region has high inter-specific variability and is useful in phylogeny (Van Doninck et al. 2002; Gottschling et al. 2005) and for determination purposes (Joseph et al. 1999; Nikoloudakis et al. 2008), especially in hybrid complexes (Malécot et al. 2009). Ninety-one individuals were collected in Europe and Asia at 28 localities (sample 1, Table 1). Additionally, 93 specimens were collected in southern France at eight localities (sample 2, locality information was given by Pagano et al. 2001a). DNA was isolated from tissue (blood, muscle, and buccal swabs) using QIAmp blood and tissue kits (Qiagen GmbH, Hilden, Germany) or the 5% Chelex 100 ion-exchange resin method (Walsh et al. 1991). Before DNA extraction, ethanol-preserved material was soaked in three changes of distilled water over a 48-h period.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, drug-induced reaction that involves both the skin and the viscera. Evidence for reactivation of herpes family viruses has been seen in some DRESS patients. To understand the immunological components of DRESS and their relationship to viral reactivation, we prospectively assessed 40 patients exhibiting DRESS in response to carbamazepine, allopurinol, or sulfamethoxazole. Peripheral blood T lymphocytes from the patients were evaluated for phenotype, cytokine secretion, and repertoire of CD4+ and CD8+ and for viral reactivation. We found Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), or HHV-7 reactivation in 76% of the patients. In all patients, circulating CD8+ T lymphocytes were activated, exhibited increased cutaneous homing markers, and secreted large amounts of tumor necrosis factor-alpha and interferon-gamma. The production of these cytokines was particularly high in patients with the most severe visceral involvement. In addition, expanded populations of CD8+ T lymphocytes sharing the same T cell receptor repertoire were detected in the blood, skin, liver, and lungs of patients. Nearly half of these expanded blood CD8+ T lymphocytes specifically recognized one of several EBV epitopes. Finally, we found that the culprit drugs triggered the production of EBV in patients' EBV-transformed B lymphocytes. Thus, cutaneous and visceral symptoms of DRESS are mediated by activated CD8+ T lymphocytes, which are largely directed against herpes viruses such as EBV.

Gene flow in riverine species is constrained by the dendritic (branching) structure of the river network. Spatial genetic structure (SGS) of freshwater insects is particularly influenced by catchment characteristics and land use in the surroundings of the river. Gene flow also depends on the life cycle of organisms. Aquatic larvae mainly drift downstream whereas flying adults can disperse actively overland and along watercourses. In-stream movements can generate isolation by distance (IBD) at a local scale and differentiation between subcatchments. However, these patterns can be disrupted by overland dispersal. We studied SGS across the Loire River in the damselfly Calopteryx splendens which is able to disperse along and between watercourses. Our sampling design allowed us to test for overland dispersal effects on genetic differentiation between watercourses. Amplified fragment length polymorphism markers revealed high genetic differentiation at the catchment scale but the genetic structure did not reflect the geographical structure of sampling sites. We observed IBD patterns when considering the distance following the watercourse but also the Euclidean distance, i.e. the shortest distance, between pairs of sites. Altogether, our results support the hypothesis of overland dispersal between watercourses. From a conservation perspective, attention should be paid to the actual pathways of gene flow across complex landscapes such as river networks.

ISBN: 978-90-481-2426-8; Dynamic System Reconfiguration in Heterogeneous Platforms defines the MORPHEUS platform that can join the performance density advantage of reconfigurable technologies and the easy control capabilities of general purpose processors. It consists of a System-on-Chip made of a scalable system infrastructure hosting heterogeneous reconfigurable accelerators, providing dynamic reconfiguration capabilities and data-stream management capabilities. Moreover a toolset which offers a software-oriented approach for implementing data intensive applications on the chip is presented. The toolset provides application design process based on high level programming languages as much as possible. Various applications from differnt domains have been selected to drive the development of the project in assessing the MORPHEUS concept about its computing performance, utilization flexibility and productivity. The emerging IEEE 802.16j standard for Mobile Broadband Wireless Access systems is the base for a first type of applications. The second application is in the area of telecommunication networks which requires data rates up to 40 Gbit/s per single line. A third application is about huge digital postprocessing of the films captured by digital camera or film scanners in resolutions up to 4K. The fourth application is about image processing for intelligent cameras.

Université d'Angers, Laboratoire Paysages & Biodiversité; International audience; We have developed eight di- and tetranucleotide Lissotriton microsatellite markers. Eight loci were polymorphic in the palmate newt Lissotriton helveticus and six were polymorphic in the smooth newt L. vulgaris. Polymorphism detected in 33 and 37 individuals per species ranged from 3 to 15 alleles. These markers are suitable for the investigation of population structure, genetic variation and taxonomic identification in the two focal species, and may also be of use in other Lissotriton-Triturus species.

International audience; Physical paleoaltimetric methods are increasingly used to estimate the amount and timing of surface uplift in orogens. Because the rise of mountains creates new ecosystems and triggers evolutionary changes, biological data may also be used to assess the development and timing of regional surface uplift. Here we apply this idea to the Peruvian Andes through a molecular phylogeographic and phylochronologic analysis of Globodera pallida, a potato parasite nematode that requires cool temperatures and thus thrives above 2.0?2.5 km in these tropical highlands. The Peruvian populations of this species exhibit a clear evolutionary pattern with deeper, more ancient lineages occurring in Andean southern Peru and shallower, younger lineages occurring progressively northwards. Genetically diverging G. pallida populations thus progressively colonized highland areas as these were expanding northwards, demonstrating that altitude in the Peruvian Andes was acquired longitudinally from south to north, i.e. in the direction of decreasing orogenic volume. This phylogeographic structure is recognized in other, independent highland biotaxa, and point to the Central Andean Orocline (CAO) as the region where high altitudes first emerged. Moreover, molecular clocks relative to Andean taxa, including the potato?tomato group, consistently estimate that altitudes high enough to induce biotic radiation were first acquired in the Early Miocene. After calibration by geological and biological tie-points and intervals, the phylogeny of G. pallida is used as a molecular clock, which estimates that the 2.0?2.5 km threshold elevation range was reached in the Early Miocene in southernmost Peru, in the Middle and Late Miocene in the Abancay segment (NW southern Peru), and from the latest Miocene in central and northern Peru. Although uncertainties attached to phylochronologic ages are significantly larger than those derived from geochronological methods, these results are fairly consistent with coeval geological phenomena along the Peruvian Andes. They strongly suggest that orogenic volume initially developed in the CAO during most of the Miocene until a breakthrough in the latest Miocene allowed the northward propagation of crustal thickening into central and northern Peru, possibly by ductile crustal flow from the CAO. Such a combined phylogeographic and phylochronologic approach to regional uplift opens perspectives to estimate the direction(s) and timing of acquisition of altitude over other Cenozoic orogens.

This paper presents a general system-level simulation and testing methodology for reconfigurable System-on-Chips, starting from behavioral specifications of system activities to multilevel simulations of accelerated tasks running on the reconfigurable circuit. The system is based on a common objectoriented environment that offers valuable debugging and probing facilities as well as integrated testing features. Our system brings these benefits to the hardware simulation, while enforcing validation through characterization tests and interoperability through on-demand mainstream tools connections. This framework has been partially developed in the scope of the EU Morpheus project and is used to validate our contribution to the spatial design task.

International audience; The cyst nematode Globodera pallida is a major pest of potato in South America where this specialist parasite is native. To investigate its phylogeography, we have genotyped individuals from 42 Peruvian populations using mitochondrial and nuclear molecular markers. A clear south-to-north phylogeographical pattern was revealed with five well-supported clades. The clade containing the southern populations is genetically more diverse and forms the most basal branch. The large divergence among cytochrome b haplotypes suggests that they diverged before human domestication of potato. As the nematodes studied have been sampled on cultivated potato, multiple host-shifts from wild to cultivated potatoes must have occurred independently in each clade. We hypothesise that this south-to-north pattern took place during the uplift of the Andes beginning 20 My ago and following the same direction. To our knowledge, this is the first study of a plant parasite sampled on cultivated plants revealing an ancient phylogeographical pattern

Although numerous species are distributed in discrete populations easily recognised by geographical barriers, continuous populations are a common feature of plants or marine organisms. This is particularly true for soil organisms as their habitat is continuous and their range cannot easily be assessed as they are buried below ground. In the case of organisms for which standard methods such as Capture/Mark/Recapture cannot be used, population genetics provide a straightforward approach to delimitate populations. In this study, we have pursued this topic with a soil-dwelling nematode ( Globodera pallida ), which parasitises potato roots and is indigenous to South America. Potential barriers to gene flow were identified using the analysis of the F ST /(1− F ST ) ratio against geographical distance and spatial autocorrelation combined with model-based clustering algorithm. Inside regions, neither genetic differentiation nor isolation by distance (IBD) occur among fields less than 50 km distant. We hypothesise that the large amount of gene flow revealed by the absence of genetic structure of this organism could be due to large passive dispersion inside an agronomic area where G. pallida has a continuous distribution and is found at high density. The first evidence of genetic differentiation appeared when a field was separated from others by an area free of farms (where G. pallida is absent or rare). Among regions, a high genetic structure coupled with an IBD pattern occurs as the consequences of the limitations of passive dispersal across deep valleys or high mountains. To our knowledge, this is the first study identifying the spatial limit of a population for a plant nematode parasite.

SummarySuppurative panniculitis usually occurs among immunocompromised patients and can be caused by opportunistic pathogens or by secondary infectious lesions in the context of septicemia. Herein we report the case of an 82-year-old woman with multiple red nodules on the leg caused by Pseudomonas aeruginosa, not related to a blood disseminated infection. The present case represents an unusual presentation of indolent suppurative panniculitis caused by P. aeruginosa.

Background Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced reaction that involves both the skin and the viscera. Several herpesvirus family members like EBV or HHV-6 can be detected coincidently with various clinical symptoms in DRESS. In addition, we have previously identified activated EBV specific cytotoxic CD8+ T cells as major actors in the pathophysiology of DRESS. In vitro, we have showed that DRESS inducer drugs increase production of EBV virus only on B-LCL lines from DRESS patients. However, drug effect on cytokines secretion has not been studied. Gene expression profiling of DRESS patients’ PBMC revealed that IL-10 and TNF-a were two of the most upregulated mRNA. We thus measured IL-10 and TNF-a secretion levels in DRESS patients’ serum and B-LCL lines following incubation with drugs.

Tattooing is common worldwide.1 Various infections have been reported, including local infections mainly due to pyogenic bacteria and systemic infections such as hepatitis B and C and HIV.2 3 We report a large outbreak of Mycobacterium chelonae skin infection occurring in France over eight months that was related to contaminated ink. Forty eight patients presented with skin lesions, mainly pustules, occurring from 3 to 35 …

The transcriptional control of CD1d-restricted NKT cell development has remained elusive. We report that PLZF (promyelocytic leukemia zinc finger; Zbtb16), a member of the BTB/POZ-ZF family of transcription factors which includes the CD4 lineage-specific c-Krox (Th-POK, Zbtb7b), is exquisitely specific to CD1d-restricted NKT cells and human MR1-specific MAIT cells. PLZF was induced immediately after positive selection of NKT cell precursors and PLZF-deficient NKT cells failed to undergo the intrathymic expansion and effector differentiation that characterize their lineage. Instead, they preserved a naïve phenotype and were directed to lymph nodes. Conversely, transgenic expression of PLZF induced CD4 thymocytes to acquire effector differentiation and migrate to non-lymphoid tissues. We suggest that PLZF is a transcriptional signature of NKT cells that directs their innate-like effector differentiation during thymic development.

Read about the roots of GEOTABS and get to know today's remarkable hybridGEOTABS buildings in Europe. Explore the state-of-the-art and new developments in the design and control of low-carbon storage-integrated systems. Find out how hybridGEOTABS reunites architecture with technology, and comfort with sustainability!, This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 723649