The place preference task: a new tool for studying the relation between behavior and place cell activity in rats

This study describes a task that combines random searching with goal directed navigation. The testing was conducted on a circular elevated open field (80 cm in diameter), with an unmarked target area (20 cm in diameter) in the center of 1 of the 4 quadrants. Whenever the rat entered the target area, the computerized tracking system released a pellet to a random point on the open field. Rats were able to learn the task under light and in total darkness, and on a stable or a rotating arena. Visual information was important in light, but idiothetic information became crucial in darkness. Learning of a new position was quicker under light than in total darkness on a rotating arena. The place preference task should make it possible to study place cells (PCs) when the rats use an allothetic (room frame) or idiothetic (arena frame) representation of space and to compare the behavioral response with the PCs' activity.

Preliminary slope mass movement susceptibility mapping using DEM and LiDAR DEM

Hazard mapping in mountainous areas at the regional scale has greatly changed since the 1990s thanks to improved digital elevation models (DEM). It is now possible to model slope mass movement and floods with a high level of detail in order to improve geomorphologic mapping. We present examples of regional multi-hazard susceptibility mapping through two Swiss case studies, including landslides, rockfall, debris flows, snow avalanches and floods, in addition to several original methods and software tools. The aim of these recent developments is to take advantage of the availability of high resolution DEM (HRDEM) for better mass movement modeling. Our results indicate a good correspondence between inventories of hazardous zones based on historical events and model predictions. This paper demonstrates that by adapting tools and methods issued from modern technologies, it is possible to obtain reliable documents for land planning purposes over large areas.

Of housing and politics : mapping political opportunities for mobilising in Bangalore, India

Quelles sont les conditions pour l'émergence d'une mobilisation sociale en faveur du logement convenable dans la métropole de Bangalore (Inde)? Cette question, qui est au coeur de cette thèse, est particulièrement pertinente dans le contexte d'une ville où 1,7 million de personnes, soit un cinquième de la population, vit dans des bidonvilles. L'absence d'un mouvement mettant en cause l'échec des politiques publiques du logement est intéressante dans la mesure où l'Inde a hérité un système de gouvernance colonial et d'une tradition de mouvements sociaux. Pour répondre à ce questionnement, un cadre théorique issu de la littérature sur les mouvements sociaux est développé. Il s'articule autour des liens entre les opportunités politiques au niveau macro et les répertoires d'action des organisations de mouvement social (OMS) au niveau méso, de la tension entre la formalité de la loi et des politiques publiques et l'informalité des circuits d'échange, de la corruption et du clientélisme, et enfin, se focalise sur les systèmes de discours de caste et de la citoyenneté et de leur concrétisation dans des systèmes d'organisations et de réseaux sociaux. Ce cadre théorique permet d'étudier empiriquement la question à travers quatre OMS dans la ville de Bangalore. Les résultats mettent en avant l'existence de mécanismes complexes. Les opportunités politiques formelles n'étant ouvertes que sur le plan rhétorique, elles ne peuvent être véritablement utilisées que par des moyens légaux ou contentieux, ce qui nécessite des compétences sociales dont la plupart des habitants des bidonvilles sont dépourvus. L'inadéquation entre les ressources à disposition pour les logements sociaux et les besoins très importants des pauvres, donne un poids politique considérable aux acteurs en charge de l'attribution de ces ressources rares. Cet état de fait a des répercussions sur la politique électorale. Les habitants des bidonvilles représentant un poids électoral important, ils sont mobilisés à travers de pratiques clientélistes. La corruption et le clientélisme se nourrissent mutuellement pour maintenir une certaine dépendance des habitants. Les OMS qui développent un répertoire discursif remettant en cause le système de caste et qui encouragent une conscience citoyenne, se sont avérées les plus durables pour résister à la cooptation des forces politiques. Cette recherche empirique met en lumière l'inadéquation entre les prescriptions formelles dans le domaine de la gouvernance des besoins humains, tels que le logement, et les pratiques réelles sur le terrain. Cette recherche appelle à réfléchir au-delà de la diffusion du discours sur la « bonne gouvernance » vers des formes de « gouvernance vernaculaire » qui prendrait au sérieux l'informalité en développant une compréhension des avantages à court terme pour les personnes marginalisées dans la ville et les effets à long terme sur la pratique démocratique. - What are the conditions for the emergence of a social movement on the issue of adequate housing in the metropolitan city of Bangalore (India)? This question is at the heart of this dissertation and is particularly pertinent against the background that an estimated 1.7 million or about 20% of the city's population lives in slums. The absence of a movement addressing the failure of public housing policy despite India having inherited colonial systems of governance and traditions of movement is noteworthy. Answers are sought within a theoretical framework stemming from social movement theories that incorporates three linkages articulating around: Macro-level political opportunities and meso-level action repertoires of social movement organisations (SMOs), tensions between the formality of law, policy and the informality of exchange circuits of corruption and clientelism and finally around systems of discourses of caste and citizenship and their instantiation in concrete systems of social organisations and networks. This thesis is empirically investigated through a qualitative case study research design involving four sampled social movement organisations. The results bring complex mechanisms to the fore. Formal political opportunities are only rhetorically open and have to be cracked through legal weaponry or contentious escalation, which requires considerable social skills that slum-dwellers often lack. The inadequacy between the few housing resources and the vast number of slum-dwellers transform housing benefits and urban service provisions into political currency. Such a state of affairs has serious repercussions on conditions for mobilisation. They become imbricated with electoral logic, in which slum-dwellers represent large vote-banks and where corruption and clientelism feed each other to maintain a certain dependency of the poor. SMOs deploying a discursive repertoire that questioned the caste system and encouraged a pursuit of citizenship proved to be the most sustainable to resist co-option from political forces. This empirical investigation brings to light the mismatch between the formal prescriptions in the domain of the governance of basic human needs such as housing and the real practices on the ground. This research calls to reflect beyond the inadequacy of the diffused « good governance » discourse towards forms of « vernacular governance » that take informality seriously in understanding the short-term benefits for the marginalised in the city and the long-term effects on democratic practice.

In vivo fate mapping with SCL regulatory elements identifies progenitors for primitive and definitive hematopoiesis in mice.

One of the principal issues facing biomedical research is to elucidate developmental pathways and to establish the fate of stem and progenitor cells in vivo. Hematopoiesis, the process of blood cell formation, provides a powerful experimental system for investigating this process. Here, we employ transcriptional regulatory elements from the stem cell leukemia (SCL) gene to selectively label primitive and definitive hematopoiesis. We report that SCL-labelled cells arising in the mid to late streak embryo give rise to primitive red blood cells but fail to contribute to the vascular system of the developing embryo. Restricting SCL-marking to different stages of foetal development, we identify a second population of multilineage progenitors, proficient in contributing to adult erythroid, myeloid and lymphoid cells. The distinct lineage-restricted potential of SCL-labelled early progenitors demonstrates that primitive erythroid cell fate specification is initiated during mid gastrulation. Our data also suggest that the transition from a hemangioblastic precursors with endothelial and blood forming potential to a committed hematopoietic progenitor must have occurred prior to SCL-marking of definitive multilineage blood precursors.

Monitoring procalcitonin in febrile neutropenia: what is its utility for initial diagnosis of infection and reassessment in persistent Fever?

Background: Management of febrile neutropenic episodes (FE) is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT) in FE for initial diagnosis of infection and reassessment in persistent fever.Methods: PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples): 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS), 68 clinically documented infections (CDI, 35%; 39 deep-seated), and 61 fever of unexplained origin (FUO, 31.5%).Results: At fever onset median PCT was 190 pg/mL (range 30-26'800), without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80-86350) vs. FUO (205, 33-771; p<0.001). PCT >500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570-771). A PCT peak >500 pg/mL (1196, 524-11950) occurred beyond 3 days of persistent fever in 17/21 (81%) invasive fungal diseases (IFD). This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1-23) vs. 10 (3-22; p = 0.026), respectively.Conclusion: While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses

Automatic Mapping and Classification of Spatial Environmental Data

The paper deals with the development and application of the generic methodology for automatic processing (mapping and classification) of environmental data. General Regression Neural Network (GRNN) is considered in detail and is proposed as an efficient tool to solve the problem of spatial data mapping (regression). The Probabilistic Neural Network (PNN) is considered as an automatic tool for spatial classifications. The automatic tuning of isotropic and anisotropic GRNN/PNN models using cross-validation procedure is presented. Results are compared with the k-Nearest-Neighbours (k-NN) interpolation algorithm using independent validation data set. Real case studies are based on decision-oriented mapping and classification of radioactively contaminated territories.

Genetic removal of tri-unsaturated fatty acids suppresses developmental and molecular phenotypes of an Arabidopsis tocopherol-deficient mutant. Whole-body mapping of malondialdehyde pools in a complex eukaryote.

Malondialdehyde (MDA) is a small, ubiquitous, and potentially toxic aldehyde that is produced in vivo by lipid oxidation and that is able to affect gene expression. Tocopherol deficiency in the vitamin E2 mutant vte2-1 of Arabidopsis thaliana leads to massive lipid oxidation and MDA accumulation shortly after germination. MDA accumulation correlates with a strong visual phenotype (growth reduction, cotyledon bleaching) and aberrant GST1 (glutathione S-transferase 1) expression. We suppressed MDA accumulation in the vte2-1 background by genetically removing tri-unsaturated fatty acids. The resulting quadruple mutant, fad3-2 fad7-2 fad8 vte2-1, did not display the visual phenotype or the aberrant GST1 expression observed in vte2-1. Moreover, cotyledon bleaching in vte2-1 was chemically phenocopied by treatment of wild-type plants with MDA. These data suggest that products of tri-unsaturated fatty acid oxidation underlie the vte2-1 seedling phenotype, including cellular toxicity and gene regulation properties. Generation of the quadruple mutant facilitated the development of an in situ fluorescence assay based on the formation of adducts of MDA with 2-thiobarbituric acid at 37 degrees C. Specificity was verified by measuring pentafluorophenylhydrazine derivatives of MDA and by liquid chromatography analysis of MDA-2-thiobarbituric acid adducts. Potentially applicable to other organisms, this method allowed the localization of MDA pools throughout the body of Arabidopsis and revealed an undiscovered pool of the compound unlikely to be derived from trienoic fatty acids in the vicinity of the root tip quiescent center.

Kernel-based mapping of orographic rainfall enhancement in the Swiss Alps as detected by weatherradar

In this paper, we develop a data-driven methodology to characterize the likelihood of orographic precipitation enhancement using sequences of weather radar images and a digital elevation model (DEM). Geographical locations with topographic characteristics favorable to enforce repeatable and persistent orographic precipitation such as stationary cells, upslope rainfall enhancement, and repeated convective initiation are detected by analyzing the spatial distribution of a set of precipitation cells extracted from radar imagery. Topographic features such as terrain convexity and gradients computed from the DEM at multiple spatial scales as well as velocity fields estimated from sequences of weather radar images are used as explanatory factors to describe the occurrence of localized precipitation enhancement. The latter is represented as a binary process by defining a threshold on the number of cell occurrences at particular locations. Both two-class and one-class support vector machine classifiers are tested to separate the presumed orographic cells from the nonorographic ones in the space of contributing topographic and flow features. Site-based validation is carried out to estimate realistic generalization skills of the obtained spatial prediction models. Due to the high class separability, the decision function of the classifiers can be interpreted as a likelihood or susceptibility of orographic precipitation enhancement. The developed approach can serve as a basis for refining radar-based quantitative precipitation estimates and short-term forecasts or for generating stochastic precipitation ensembles conditioned on the local topography.

Mapping the transcription start points of the Staphylococcus aureus eap, emp, and vwb promoters reveals a conserved octanucleotide sequence that is essential for expression of these genes.

Mapping the transcription start points of the eap, emp, and vwb promoters revealed a conserved octanucleotide sequence (COS). Deleting this sequence abolished the expression of eap, emp, and vwb. However, electrophoretic mobility shift assays gave no evidence that this sequence was a binding site for SarA or SaeR, known regulators of eap and emp.

New Developments and Applications of the MP2RAGE Sequence - Focusing the Contrast and High Spatial Resolution R1 Mapping.

MR structural T1-weighted imaging using high field systems (>3T) is severely hampered by the existing large transmit field inhomogeneities. New sequences have been developed to better cope with such nuisances. In this work we show the potential of a recently proposed sequence, the MP2RAGE, to obtain improved grey white matter contrast with respect to conventional T1-w protocols, allowing for a better visualization of thalamic nuclei and different white matter bundles in the brain stem. Furthermore, the possibility to obtain high spatial resolution (0.65 mm isotropic) R1 maps fully independent of the transmit field inhomogeneities in clinical acceptable time is demonstrated. In this high resolution R1 maps it was possible to clearly observe varying properties of cortical grey matter throughout the cortex and observe different hippocampus fields with variations of intensity that correlate with known myelin concentration variations.

Mechanism of reduction of virus release and cell-cell fusion in persistent canine distemper virus infection.

Canine distemper virus (CDV), a mobillivirus related to measles virus causes a chronic progressive demyelinating disease, associated with persistence of the virus in the central nervous system (CNS). CNS persistence of morbilliviruses has been associated with cell-to-cell spread, thereby limiting immune detection. The mechanism of cell-to-cell spread remains uncertain. In the present study we studied viral spread comparing a cytolytic (non-persistent) and a persistent CDV strain in cell cultures. Cytolytic CDV spread in a compact concentric manner with extensive cell fusion and destruction of the monolayer. Persistent CDV exhibited a heterogeneous cell-to-cell pattern of spread without cell fusion and 100-fold reduction of infectious viral titers in supernatants as compared to the cytolytic strain. Ultrastructurally, low infectious titers correlated with limited budding of persistent CDV as compared to the cytolytic strain, which shed large numbers of viral particles. The pattern of heterogeneous cell-to-cell viral spread can be explained by low production of infectious viral particles in only few areas of the cell membrane. In this way persistent CDV only spreads to a small proportion of the cells surrounding an infected one. Our studies suggest that both cell-to-cell spread and limited production of infectious virus are related to reduced expression of fusogenic complexes in the cell membrane. Such complexes consist of a synergistic configuration of the attachment (H) and fusion (F) proteins on the cell surface. F und H proteins exhibited a marked degree of colocalization in cytolytic CDV infection but not in persistent CDV as seen by confocal laser microscopy. In addition, analysis of CDV F protein expression using vaccinia constructs of both strains revealed an additional large fraction of uncleaved fusion protein in the persistent strain. This suggests that the paucity of active fusion complexes is due to restricted intracellular processing of the viral fusion protein.

Persistent infection of arenaviruses : molecular mechanisms and pathogenesis

Arenaviruses are enveloped negative single strand RNA viruses that include a number of important human pathogens. The most prevalent human pathogen among the arenaviruses is the Old World arenavirus Lassa virus (LASV) which is endemic in West Africa from Senegal to Cameroon. LASV is the etiologic agent of a severe viral hemorrhagic fever named Lassa fever whose mortality rate can reach 30% in hospitalized patients. One of the hallmarks of fatal arenavirus infection in humans is the absence of an effective innate and adaptive immune response. In nature, arenaviruses are carried by rodents which represent the natural reservoirs as well as the vectors for transmission. In their natural rodent reservoir, arenaviruses have the ability to establish persistent infection without any overt signs and symptoms of pathology. We believe that the modulation of the host cell's innate immunity by arenaviruses is a key determinant for persistence in the natural host and for the pathogenesis in man. In this thesis, we studied the interaction of arenaviruses with two main branches of the host's innate anti-viral defense, the type I interferon (IFN) system and virus-induced mitochondrial apoptosis. The arenavirus nucleoprotein (NP) is responsible for the anti-IFN activity of arenaviruses. Specifically, NP blocks the activation and the nuclear translocation of the transcription factor interferon regulatory factor 3 (IRF3) which leads to type I IFN production. LASV and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) NPs contain a 3'-5'exoribonuclease domain in the C terminal part that has been linked to the anti-IFN activity of NP. In the first project, we sought to identify cellular component(s) of the type I IFN induction pathway targeted by the viral NP. Our study revealed that LCMV NP prevents the activation of IRF3 by blocking phosphorylation of the transcription factor. We found that LCMV NP specifically targets the IRF-activating kinase IKKs, and this specific binding is conserved within the Arenaviridae. We could also demonstrate that LCMV NP associates with the kinase domain of IKKs involving NP's C-terminal region. Lastly, we showed that the binding of LCMV NP inhibits the kinase activity of IKKs. This study allowed the discovery of a new cellular interacting partner of arenavirus NP. This newly described association may play a role in the anti-IFN activity of arenaviruses but potentially also in other aspects of arenavirus infection. For the second project, we investigated the ability of arenaviruses to avoid and/or suppress mitochondrial apoptosis. As persistent viruses, arenaviruses evolved a "hit and stay" survival strategy where the apoptosis of the host cell would be deleterious. We found that LCMV does not induce mitochondrial apoptosis at any time during infection. Specifically, no caspase activity, no cytochrome c release from the mitochondria as well as no cleavage of poly (ADP-ribose) polymerase (PARP) were detected during LCMV infection. Interestingly, we found that virus-induced mitochondrial apoptosis remains fully functional in LCMV infected cells, while the induction of type IIFN is blocked. Since both type IIFN production and virus- induced mitochondrial apoptosis critically depend on the pattern recognition receptor (PRR) RIG-I, we examined the role of RIG-I in apoptosis in LCMV infected cells. Notably, virus- induced mitochondrial apoptosis in LCMV infected cells was found to be independent of RIG- I and MDA5, but still depended on MAVS. Our study uncovered a novel mechanism by which arenaviruses alter the host cell's pro-apoptotic signaling pathway. This might represent a strategy arenaviruses developed to maintain this branch of the innate anti-viral defense in absence of type I IFN response. Taken together, these results allow a better understanding of the interaction of arenaviruses with the host cell's innate immunity, contributing to our knowledge about pathogenic properties of these important viruses. A better comprehension of arenavirus virulence may open new avenues for vaccine development and may suggest new antiviral targets for therapeutic intervention against arenavirus infections. - Les arenavirus sont des virus enveloppés à ARN simple brin qui comportent un grand nombre de pathogènes humains. Le pathogène humain le plus important parmi les arenavirus est le virus de Lassa qui est endémique en Afrique de l'Ouest, du Sénégal au Cameroun. Le virus de Lassa est l'agent étiologique d'une fièvre hémorragique sévère appelée fièvre de Lassa, et dont le taux de mortalité peut atteindre 30% chez les patients hospitalisés. L'une des caractéristiques principales des infections fatales à arenavirus chez l'Homme est l'absence de réponse immunitaire innée et adaptative. Dans la nature, les arenavirus sont hébergés par différentes espèces de rongeur, qui représentent à la fois les réservoirs naturels et les vecteurs de transmission des arenavirus. Dans leur hôte naturel, les arenavirus ont la capacité d'établir une infection persistante sans symptôme manifeste d'une quelconque pathologie. Nous pensons que la modulation de système immunitaire inné de la cellule hôte par les arenavirus est un paramètre clé pour la persistance au sein de l'hôte naturel, ainsi que pour la pathogenèse chez l'Homme. L'objectif de cette thèse était d'étudier l'interaction des arenavirus avec deux branches essentielles de la défense antivirale innée de la cellule hôte, le système interféron (IFN) de type I et l'apoptose. La nucléoprotéine virale (NP) est responsable de l'activité anti-IFN des arenavirus. Plus spécifiquement, la NP bloque 1'activation et la translocation nucléaire du facteur de transcription IRF3 qui conduit à la production des IFNs de type I. La NP du virus de Lassa et celle du virus de la chorioméningite lymphocytaire (LCMV), l'arénavirus prototypique, possèdent dans leur extrémité C-terminale un domaine 3'-5' exoribonucléase qui a été associé à l'activité anti-IFN de ces protéines. Dans un premier projet, nous avons cherché à identifier des composants cellulaires de la cascade de signalisation induisant la production d'IFNs de type I qui pourraient être ciblés par la NP virale. Nos recherches ont révélé que la NP de LCMV empêche 1'activation d'IRF3 en bloquant la phosphorylation du facteur de transcription. Nous avons découvert que la NP de LCMV cible spécifiquement la kinase IKKe, et que cette interaction spécifique est conservée à travers la famille des Arenaviridae. Notre étude a aussi permis de démontrer que la NP de LCMV interagit avec le domaine kinase d'IKKe et que l'extrémité C-terminale de la NP est impliquée. Pour finir, nous avons pu établir que l'association avec la NP de LCMV inhibe l'activité kinase d'IKKe. Cette première étude présente la découverte d'un nouveau facteur cellulaire d'interaction avec la NP des arenavirus. Cette association pourrait jouer un rôle dans l'activité anti-IFN des arénavirus, mais aussi potentiellement dans d'autres aspects des infections à arénavirus. Pour le second projet, nous nous sommes intéressés à la capacité des arénavirus à éviter et/ou supprimer l'apoptose mitochondriale. En tant que virus persistants, les arénavirus ont évolué vers une stratégie de survie "hit and stay" pour laquelle l'apoptose de la cellule hôte serait néfaste. Nous avons observé qu'à aucun moment durant l'infection LCMV n'induit l'apoptose mitochondriale. Spécifiquement, aucune activité de caspase, aucune libération mitochondriale de cytochrome c ainsi qu'aucun clivage de la polymerase poly(ADP-ribose) (PARP) n'a été détecté pendant l'infection à LCMV. Il est intéressant de noter que l'apoptose mitochondriale induite par les virus reste parfaitement fonctionnelle dans les cellules infectées par LCMV, alors que l'induction de la réponse IFN de type I est bloquée dans les mêmes cellules. La production des IFNs de type I et l'apoptose mitochondriale induite par les virus dépendent toutes deux du récepteur de reconnaissance de motifs moléculaires RIG-I. Nous avons, par conséquent, investigué le rôle de RIG-I dans l'apoptose qui a lieu dans les cellules infectées par LCMV lorsqu'on les surinfecte avec un autre virus pro-apoptotique. En particulier, l'apoptose mitochondriale induite par les surinfections s'est révélée indépendante de RIG-I et MDA5, mais dépendante de MAVS dans les cellules précédemment infectées par LCMV. Notre étude démontre ainsi l'existence d'un nouveau mécanisme par lequel les arénavirus altèrent la cascade de signalisation pro-apoptotique de la cellule hôte. Il est possible que les arénavirus aient développé une stratégie permettant de maintenir fonctionnelle cette branche de la défense antivirale innée en l'absence de réponse IFN de type I. En conclusion, ces résultats nous amènent à mieux comprendre l'interaction des arénavirus avec l'immunité innée de la cellule hôte, ce qui contribue aussi à améliorer notre connaissance des propriétés pathogéniques de ces virus. Une meilleure compréhension des facteurs de virulence des arénavirus permet, d'une part, le développement de vaccins et peut, d'autre part, servir de base pour la découverte de nouvelles cibles thérapeutiques utilisées dans le traitement des infections à arénavirus.