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Phosphatidylinositol transfer proteins (PITP) are a family of monomeric proteins that bind and transfer phosphatidylinositol and phosphatidylcholine between membrane compartments. They are required for production of inositol and diacylglycerol second messengers, and are found in most metazoan organisms. While PITPs are known to carry out crucial cell-signaling roles in many organisms, the structure, function and evolution of the majority of family members remains unexplored; primarily because the ubiquity and diversity of the family thwarts traditional methods of global alignment. To surmount this obstacle, we instead took a novel approach, using MEME and a parsimony-based analysis to create a cladogram of conserved sequence motifs in 56 PITP family proteins from 26 species. In keeping with previous functional annotations, three clades were supported within our evolutionary analysis; two classes of soluble proteins and a class of membrane-associated proteins. By, focusing on conserved regions, the analysis allowed for in depth queries regarding possible functional roles of PITP proteins in both intra- and extra- cellular signaling.

ChemVassa, a new chemical structure search technology, was developed to allow rapid in silico screening of compounds for hit and hit-to-lead identification in drug development. It functions by using a novel type of molecular descriptor that examines, in part, the structure of the small molecule undergoing analysis, yielding its “information signature.” This descriptor takes into account the atoms, bonds, and their positions in 3-dimensional space. For the present study, a database of ChemVassa molecular descriptors was generated for nearly 16 million compounds (from the ZINC database and other compound sources), then an algorithm was developed that allows rapid similarity searching of the database using a query molecular descriptor (e.g., the signature of atorvastatin, below). A scoring metric then allowed ranking of the search results. We used these tools to search a subset of drug-like molecules using the signature of a commercially successful statin, atorvastatin (Lipitor™). The search identified ten novel compounds, two of which have been demonstrated to interact with HMG-CoA reductase, the macromolecular target of atorvastatin. In particular, one compound discussed in the results section tested successfully with an IC50 of less than 100uM and a completely novel structure relative to known inhibitors. Interactions were validated using computational molecular docking and an Hmg-CoA reductase activity assay. The rapidity and low cost of the methodology, and the novel structure of the interactors, suggests this is a highly favorable new method for hit generation.

Trichophyton tonsurans infections occur in various host populations, on various body sites and with varying degrees of inflammation. This investigation was undertaken to determine whether fungal factors could explain the degree of severity in clinical symptomatology among infected children. Otherwise healthy children (n=54) presenting with tinea capitis were enrolled in this study. A thorough history was performed, the extent and severity of infection graded and a fungal specimen collected from each child. Strain type was determined by genotyping for 11 sequence variations in the rDNA and ALP1 loci. Secreted protease activity was quantitated after 5 days of growth in aqueous medium. Forty participants were evaluable. Infection duration ranged from 1 day to 3 years and clinical severity score (CSS) from 4-19. Seventeen unique fungal genotypes were present. Keratinase, collagenase and elastase activity varied 32.7-fold, 64.9-fold and 303.3-fold, respectively. A significant association was observed between genotype and disease severity with the rDNA sequence variations accounting for over 50% of the variation observed in CSS (r2=0.539; P

International audience; Climatic oscillations and anthropogenic perturbations have a great influence, at multiple spatial and time scales, on hydrosedimentary dynamics and the morphology of rivers. In particular, numerous studies emphasize on changes in fluvial regimes occurring during the post-LGM deglaciation period. Though most of the Holocene evolution of rivers seems to be linked to climatic fluctuations, it is essential, when focusing on historical periods (i.e. post- Bronze Age), to take into account and try to quantify the influence of anthropic activities on such an evolution.The Cosson watershed, located south of the middle Loire river section, flows on the Miocene fluvio-lacustrine formations of the Sologne region.Alluvial terraces in the watershed give evidence of a common evolution between the Loire and Cosson rivers before they separate during mid-Pleistocene times. In the Chambord National Domain, analyses of high-resolution Digital Elevation Models derived from airborne Lidar data show a complex network of multiple channels on the Cosson river (channeled since 15th century times) floodplain surface. Core drillings have been carried out in the floodplain to precise the Holocene hydrosedimentary dynamics of the river. Ages of alluvial deposits have been obtained using radiocarbon dating. Results show that the Holocene period can be divided in two principal sequences : a basal sequence, several metres thick, composed of coarse alluvium (coarse sand and gravels) and a top sequence about 1m-thick consisting in silty-clayey materials alternating with sandy layers. Datings place the transition between the two sequences around 1500 and 1800 yrs BP, whereas no major change seems to occur in hydrosedimentary dynamics at the base of the Holocene. Complementary work on the alluvium, such as grain-size, organic matterand palynological analyses are being carried out. Such analyses will allow to characterize sedimentary sources, better constrain the watershedpaleoenvironments, and precise the respective influence of climatic and anthropogenic forcings on the Holocene hydrosedimentary dynamics in theCosson lowland setting, where anthropic activities (prior and posterior to the edification of the Chambord royal castle) have been well documented by archeological and historical studies.

International audience; Les variations climatiques naturelles et les perturbations liées aux activités anthropiques ont une grande influence, à différentes échelles spatiotemporelles, sur la dynamique hydrosédimentaire et la morphologie des cours d'eau. De nombreuses études précisent notamment les modalités de modifications de régime fluviatile postérieurs au dernier maximum glaciaire. Si la majeure partie de l'évolution holocène des cours d'eau semble liée aux fluctuations climatiques, il est fondamental, pour la période historique (i.e., post-Age du Bronze), de prendre en compte et d'estimer l'influence anthropique, via la mise en culture, sur cette évolution. Le bassin versant du Cosson, au sud de la Loire entre Orléans et Blois,draine les formations miocènes de la Sologne. Les terrasses alluviales du Cosson témoignent d'une histoire commune avec la Loire, avantindividualisation de ces cours d'eau au cours du Pléistocène moyen. Dans le Domaine National de Chambord, l'analyse de MNT issus d'une acquisition LIDAR aéroportée montre en surface de la plaine d'inondation du Cosson (canalisé depuis le 15ème siècle) la trace de multiples chenaux. Lors de cette étude, nous avons acquis des données de résistivité électrique et analysé des sondages carottés. Les dépôts alluviaux ont été contraints chronologiquement par datations au radiocarbone.Les premiers résultats permettent de distinguer pour la période Holocène deux séquences majeures : une séquence basale épaisse de plusieurs mètres d'alluvions grossières (sables grossiers et graviers dominants) et une séquence sommitale constituée d'environ 1m de matériel silto-argileux. Les âges obtenus situent la transition entre ces deux séquences entre 200 et 500 ap. J-C, alors qu'aucune modification majeure du régime fluviatile ne semble intervenir au début de l'Holocène. Des analyses fines des alluvions sont en cours : granulométrie, nature et degré de maturation de la matière organique, palynologie... Ces analyses permettront de caractériser les sources sédimentaires et contraindre les paléoenvironnements dans le bassin versant, afin de préciser l'influence respective des facteurs forçants climatiques et anthropiques sur la dynamique fluviatile, dans ce contexte de cours d'eau de plaine où l'activité humaine (antérieure et postérieure à la construction du château de Chambord) est bien documentée par les prospections archéologiques et les écrits historiques.

International audience; For extraction and characterization of archeological structures from LIDar data, most studies focus on manual spotting (vectorization) or automatic image processing (IP), while few studies have examined semi-automated methods based on machine learning (ML). In the context of the Solidar project, after trying to use classical image processing techniques, we propose to reflect on elements to be integrated in ML approaches for a better and a more flexible extraction and characterization of archeological structures discovered in the LiDAR datasets. Indeed, the LiDAR data reveal many varied remains over large geographic areas. Manual digitizing of these remains is a time-consuming activity and does not guarantee an exhaustive recognition of features. This article proposes to present: (1) the archaeological context of this work, (2) the searched objects in this study, (3) the first tests and (4) how the data will be processed in the near future.

Forests are environments favourable to the conservation of anthropogenic vestiges because the action of erosion is less marked in forests than in open areas. The archaeological work conducted in these forests focuses on all kinds of vestiges preserved by the cover of vegetation as well as human forestry activities (Dupouey et al., 2007). These two approaches were used within the framework of the SOLiDAR programme, namely thanks to the LiDAR remote detection survey conducted during the winter of 2015, the first findings of which are presented here. The area studied includes the Chambord national estate and the state-owned forests of Boulogne, Russy and Blois, representing a woodland area of close to 25 000 hectares. In addition to pedestrian surveys conducted over a period of 15 years, the LiDAR survey made it possible to identify vestiges which are invisible to the naked eye and which concern the former exploitation of the forest as well as prior human settlements. This diachronic approach, combining sources widely used by archaeologists (archaeological digs and excavations, archives, geomorphological and ecological surveys) and LiDAR technology makes it possible to use regressive analysis in the long-term study of forestry landscapes., La forêt est un milieu propice à la conservation des vestiges anthropiques, car l'action de l'érosion y est moins importante que dans les milieux ouverts. L'archéologie dans ce milieu porte, d'une part, sur les vestiges de toutes natures conservés sous le couvert forestier et, d'autre part, sur les activités humaines liées à l'exploitation de la forêt (Dupouey et al., 2007). Ces deux approches ont été mises en œuvre dans le cadre du programme SOLiDAR, notamment grâce à une campagne de télédétection LiDAR menée durant l'hiver 2015, dont nous présentons ici les premiers résultats. La zone étudiée comprend le domaine national de Chambord et les forêts domaniales de Boulogne, Russy et Blois, soit un espace forestier de près de 25 000 ha. En complément des campagnes de prospection pédestres menées pendant 15 ans, le relevé LiDAR a permis la reconnaissance de vestiges invisibles à l'œil nu touchant à une exploitation ancienne de la forêt et à des occupations humaines antérieures à la forêt. Cette approche diachronique, conjuguant les sources habituellement utilisées par les archéologues (fouilles et prospections archéologiques, archives, études géomorphologiques et écologiques) et la technologie LiDAR, permet une démarche régressive pour l'étude du paysage forestier dans le temps long.

International audience

International audience