Programming of marginal zone B-cell fate by basic Kruppel-like factor (BKLF/KLF3).

Splenic marginal zone (MZ) B cells are a lineage distinct from follicular and peritoneal B1 B cells. They are located next to the marginal sinus where blood is released. Here they pick up antigens and shuttle the load onto follicular dendritic cells inside the follicle. On activation, MZ B cells rapidly differentiate into plasmablasts secreting antibodies, thereby mediating humoral immune responses against blood-borne type 2 T-independent antigens. As Krüppel-like factors are implicated in cell differentiation/function in various tissues, we studied the function of basic Krüppel-like factor (BKLF/KLF3) in B cells. Whereas B-cell development in the bone marrow of KLF3-transgenic mice was unaffected, MZ B-cell numbers in spleen were increased considerably. As revealed in chimeric mice, this occurred cell autonomously, increasing both MZ and peritoneal B1 B-cell subsets. Comparing KLF3-transgenic and nontransgenic follicular B cells by RNA-microarray revealed that KLF3 regulates a subset of genes that was similarly up-regulated/down-regulated on normal MZ B-cell differentiation. Indeed, KLF3 expression overcame the lack of MZ B cells caused by different genetic alterations, such as CD19-deficiency or blockade of B-cell activating factor-receptor signaling, indicating that KLF3 may complement alternative nuclear factor-κB signaling. Thus, KLF3 is a driving force toward MZ B-cell maturation.

Age-related changes in the bimanual advantage and in brain oscillatory activity during tapping movements suggest a decline in processing sensory reafference

Deficits in the processing of sensory reafferences have been suggested as accounting for age-related decline in motor coordination. Whether sensory reafferences are accurately processed can be assessed based on the bimanual advantage in tapping: because of tapping with an additional hand increases kinesthetic reafferences, bimanual tapping is characterized by a reduced inter-tap interval variability than unimanual tapping. A suppression of the bimanual advantage would thus indicate a deficit in sensory reafference. We tested whether elderly indeed show a reduced bimanual advantage by measuring unimanual (UM) and bimanual (BM) self-paced tapping performance in groups of young (n = 29) and old (n = 27) healthy adults. Electroencephalogram was recorded to assess the underlying patterns of oscillatory activity, a neurophysiological mechanism advanced to support the integration of sensory reafferences. Behaviorally, there was a significant interaction between the factors tapping condition and age group at the level of the inter-tap interval variability, driven by a lower variability in BM than UM tapping in the young, but not in the elderly group. This result indicates that in self-paced tapping, the bimanual advantage is absent in elderly. Electrophysiological results revealed an interaction between tapping condition and age group on low beta band (14âeuro"20 Hz) activity. Beta activity varied depending on the tapping condition in the elderly but not in the young group. Source estimations localized this effect within left superior parietal and left occipital areas. We interpret our results in terms of engagement of different mechanisms in the elderly depending on the tapping mode: a âeuro~kinestheticâeuro? mechanism for UM and a âeuro~visual imageryâeuro? mechanism for BM tapping movement.

Développement d'une méthode microgravimétrique urbaine : intégration dans un SIG et application au projet du M2 lausannois

Résumé La réalisation d'une seconde ligne de métro (M2) dès 2004, passant dans le centre ville de Lausanne, a été l'opportunité de développer une méthodologie concernant des campagnes microgravimétriques dans un environnement urbain perturbé. Les corrections topographiques prennent une dimension particulière dans un tel milieu, car de nombreux objets non géologiques d'origine anthropogénique comme toutes sortes de sous-sols vides viennent perturber les mesures gravimétriques. Les études de génie civil d'avant projet de ce métro nous ont fournis une quantité importante d'informations cadastrales, notamment sur les contours des bâtiments, sur la position prévue du tube du M2, sur des profondeurs de sous-sol au voisinage du tube, mais aussi sur la géologie rencontré le long du corridor du M2 (issue des données lithologiques de forages géotechniques). La planimétrie des sous-sols a été traitée à l'aide des contours des bâtiments dans un SIG (Système d'Information Géographique), alors qu'une enquête de voisinage fut nécessaire pour mesurer la hauteur des sous-sols. Il a été alors possible, à partir d'un MNT (Modèle Numérique de Terrain) existant sur une grille au mètre, de mettre à jour celui ci avec les vides que représentent ces sous-sols. Les cycles de mesures gravimétriques ont été traités dans des bases de données Ac¬cess, pour permettre un plus grand contrôle des données, une plus grande rapidité de traitement, et une correction de relief rétroactive plus facile, notamment lorsque des mises à jour de la topographie ont lieu durant les travaux. Le quartier Caroline (entre le pont Bessières et la place de l'Ours) a été choisi comme zone d'étude. Le choix s'est porté sur ce quartier du fait que, durant ce travail de thèse, nous avions chronologiquement les phases pré et post creusement du tunnel du M2. Cela nous a permis d'effectuer deux campagnes gravimétriques (avant le creu¬sement durant l'été 2005 et après le creusement durant l'été 2007). Ces réitérations nous ont permis de tester notre modélisation du tunnel. En effet, en comparant les mesures des deux campagnes et la réponse gravifique du modèle du tube discrétisé en prismes rectangulaires, nous avons pu valider notre méthode de modélisation. La modélisation que nous avons développée nous permet de construire avec détail la forme de l'objet considéré avec la possibilité de recouper plusieurs fois des interfaces de terrains géologiques et la surface topographique. Ce type de modélisation peut s'appliquer à toutes constructions anthropogéniques de formes linéaires. Abstract The realization of a second underground (M2) in 2004, in downtown Lausanne, was the opportunity to develop a methodology of microgravity in urban environment. Terrain corrections take on special meaning in such environment. Many non-geologic anthropogenic objects like basements act as perturbation of gravity measurements. Civil engineering provided a large amount of cadastral informations, including out¬lines of buildings, M2 tube position, depths of some basements in the vicinity of the M2 corridor, and also on the geology encountered along the M2 corridor (from the lithological data from boreholes). Geometry of basements was deduced from building outlines in a GIS (Geographic Information System). Field investigation was carried out to measure or estimate heights of basements. A DEM (Digital Elevation Model) of the city of Lausanne is updated from voids of basements. Gravity cycles have been processed in Access database, to enable greater control of data, enhance speed processing, and retroactive terrain correction easier, when update of topographic surface are available. Caroline area (between the bridge Saint-Martin and Place de l'Ours) was chosen as the study area. This area was in particular interest because it was before and after digging in this thesis. This allowed us to conduct two gravity surveys (before excavation during summer 2005 and after excavation during summer 2007). These re-occupations enable us to test our modélisation of the tube. Actually, by comparing the difference of measurements between the both surveys and the gravity response of our model (by rectangular prisms), we were able to validate our modeling. The modeling method we developed allows us to construct detailed shape of an object with possibility to cross land geological interfaces and surface topography. This type of modélisation can be applied to all anthropogenic structures.

Perinuclear Mlp proteins down-regulate gene expression in response to a defect in mRNA export

Résumé Une caractéristique des cellules eucaryotes est le confinement du matériel génétique (ADN/DNA) dans le noyau. Pour décoder cette information, un ARN messager (mRNA) est d'abord transcrit sous forme d'un ARN prémessager (pré-mRNA). Ce-dernier doit subir plusieurs étapes de maturation pour aboutir à une particule ribonucléoprotéique (mRNP) qui sera exportée vers le cytoplasme et traduite en protéine. La protéine de levure Mex67p et son homologue humain TAP sont des récepteurs d'export médiant la translocation du mRNP au travers des complexes du pore nucléaire (NPC). Mex67p/TAP ne se lient pas directement au mRNA, mais nécessitent la présence de protéines adaptatrices, telles que Yra1p et son homologue humain REF1. Afin d'identifier de nouveaux facteurs impliqués dans l'export des mRNPs ou de nouvelles fonctions pour Yra1p, nous avons effectué un crible génétique avec un mutant thermosensible de Yra1p, GFP-yra 1 -8. Ce mutant présente un défaut d'export des mRNAs et une diminution des niveaux de transcrits du gène rapporteur LacZ ainsi que de certains transcrits endogènes. Nous avons trouvé que la perte de Mlp2p, ou d'une protéine hautement similaire, Mlp1p, restaure la croissance du mutant GFP-yra1-8 à température restrictive. Mlp1p et Mlp2p sont des protéines nucléaires, dont l'homologue humain est TPR. Les Mlp (myosin¬like proteins) ainsi que TPR forment des structures filamenteuses ancrées aux NPC. Bien que la fonction des Mlp ne soit pas clairement définie, un rôle dans la biogenèse et la surveillance des mRNPs a été récemment proposé. Notre étude montre que la perte des Mlp, non seulement restaure la croissance de GFP-yra1-8, mais augmente aussi les niveaux des transcrits LacZ et facilite leur apparition dans le cytoplasme. Des expériences d'immunoprécipitations de la chromatine révèlent que Mlp2p diminue le taux de synthèse du transcrit LacZ dans GFP-yra1-8. Des analyses du transcriptome montrent que Mlp2p réduit aussi les niveaux d'une population de transcrits endogènes dans le mutant. Finalement, des localisations in situ suggèrent que la transcription du rapporteur LacZ a lieu à la périphérie du noyau, à proximité des Mlp. Ainsi, les protéines Mlp pourraient préférentiellement diminuer la transcription de gènes exprimés à la périphérie nucléaire. Nous montrons aussi que Yra1p interagit génétiquement avec Nab2p une protéine liée au mRNA et impliquée dans son export, mais non avec d'autres protéines également impliquées dans l'export des mRNAs. Les résultats obtenus soutiennent un modèle où les protéines Yra1p et Nab2p sont nécessaires à l'arrimage des mRNPs sur la plate-forme des Mlp. Si ces signaux manquent ou sont défectueux, les mRNPs ne peuvent pas poursuivre leur trajet vers le canal central du NPC. Ce bloc induirait par la suite une diminution de la transcription d'une population de gènes potentiellement localisée à la périphérie nucléaire. Dans son ensemble, cette étude suggère que les protéines Mlp établissent un lien entre la transcription de certains mRNAs et leur export au travers du pore nucléaire. Summary A hallmark of the eukaryotic cell is the packaging of DNA in the nucleus. To decode the genetic information, a messenger RNA (mRNA) is first synthesized as a pre-mRNA molecule, which undergoes different maturation steps resulting in an mRNP (messenger RNA ribonucleoprotein), which can be actively transported to the cytoplasm and translated into a protein. Yeast Mex67p and its human homologue TAP are export receptors mediating mRNP translocation through the nuclear pore complex (NPC). The recruitment of Mex67p/TAP to mRNA is mediated by mRNA export adaptors of the evolutionarily conserved REF (RNA and Export Factor binding) family: yeast Yra1p and human REF1. To uncover new functions of Yra1p or new factors implicated in mRNA export, we performed a genetic screen with a themiosensitive (ts) yra1 mutant, GFP-yra1-8. This mutant exhibits mRNA export defects and a decrease in the levels of LacZ reporter and certain endogenous transcripts. We found that the loss of Mlp2p, or the related Mlp1p protein, substantially rescues the growth defect of the GFP-yra1 -8 mutant. Mlp1p and M1p2p are large non-essential proteins, homologous to human TPR, proposed to form intra-nuclear filamentous structures anchored at the NPC. Their role is not clearly defined, but they have been implicated in mRNP biogenesis and surveillance. Our study shows that loss of Mlp proteins not only restores growth of GFP-yra1-8, but also rescues LacZ mRNA levels and increases their appearance in the cytoplasm. Chromatin immunoprecipitation and pulse chase experiments indicate that Mlp2p down-regulates LacZ mRNA synthesis in GFP-yra1-8. DNA micro- array analyses reveal that Mlp2p also reduces the levels of a subset of cellular transcripts in the yra1 mutant strain. In situ localizations suggest that LacZ transcription occurs at the nuclear periphery, in close proximity to Mlp proteins. Thus, Mlp proteins may preferentially down-regulate genes expressed at the nuclear periphery. Finally, we show that Yra1p genetically interacts with the shuttling mRNA-binding protein Nab2p and that loss of Mlp proteins rescues the growth defect of yra1 and nab2, but not other mRNA export mutants. The data support a model in which Nab2p and Yra1p are required for rnRNP docking to the Mlp platform. Lack of these signals prevents mRNPs from crossing the Mlp gate. This block may then negatively feed-back on the transcription of a subset of genes, potentially located at the nuclear envelope. Overall, this study suggests that perinuclear Mlp proteins establish a link between mRNA transcription and export.

Recent advances in remote sensing image processing

Remote sensing image processing is nowadays a mature research area. The techniques developed in the field allow many real-life applications with great societal value. For instance, urban monitoring, fire detection or flood prediction can have a great impact on economical and environmental issues. To attain such objectives, the remote sensing community has turned into a multidisciplinary field of science that embraces physics, signal theory, computer science, electronics, and communications. From a machine learning and signal/image processing point of view, all the applications are tackled under specific formalisms, such as classification and clustering, regression and function approximation, image coding, restoration and enhancement, source unmixing, data fusion or feature selection and extraction. This paper serves as a survey of methods and applications, and reviews the last methodological advances in remote sensing image processing.

Gabbro, plagiogranite and associated dykes in the supra-subduction zone Evros Ophiolites, NE Greece

The incomplete Evros ophiolites in NE Greece form a NE-SW-oriented discontinuous belt in the Alpine orogen of the north Aegean. Field data, petrology and geochemistry are presented here for the intrusive section and associated mafic dykes of these ophiolites. Bodies of high-level isotropic gabbro and plagiogranite in the ophiolite suite are cross-cut by NE-SW-trending boninitic and tholeiitic-boninitic affinity dykes, respectively. The dykes fill tensile fractures or faults, which implies dyke emplacement in an extensional tectonic regime. The tholeiitic-transitional boninitic gabbro is REE- and HFS-depleted relative to N-MORB, indicating derivation from melting of a refractory mantle peridotite source. Associated boninitic dykes are slightly LREE-enriched, showing mineral and whole-rock geochemistry similar to the gabbro. The plagiogranite is a strongly REE-enriched high-silica trondhjemite, with textures and composition typical for an oceanic crust differentiate. Plagiogranite-hosted tholeiitic and transitional boninitic dykes are variably REE-enriched. Geochemical modelling indicates origin of the plagiogranite by up to 75% fractional crystallization of basaltic magma similar to that producing the associated tholeiitic dykes. All mafic rocks have high LILE/HFSE ratios and negative Ta-Nb-Ti and Ce anomalies, typical for subduction zone-related settings. The mafic rocks show a similar trace-element character to the mafic lavas of an extrusive section in Bulgaria, suggesting they both form genetically related intrusive and extrusive suites of the Evros ophiolites. The field occurrence, the structural context, the petrology and geochemical signature of the studied magmatic assemblage provide evidence for its origin in a proto-arc (fore-arc) tectonic setting, thus tracing the early stages of the tectono-magmatic evolution of Jurassic arc-marginal basin system that has generated the supra-subduction type Evros ophiolites.

Bayesian-MCMC inversion of time-lapse geophysical data to characterize vadose zone hydraulic behaviour

Geophysical methods have the potential to provide valuable information on hydrological properties in the unsaturated zone. In particular, time-lapse geophysical data, when coupled with a hydrological model and inverted stochastically, may allow for the effective estimation of subsurface hydraulic parameters and their corresponding uncertainties. In this study, we use a Bayesian Markov-chain-Monte-Carlo (MCMC) inversion approach to investigate how much information regarding vadose zone hydraulic properties can be retrieved from time-lapse crosshole GPR data collected at the Arrenaes field site in Denmark during a forced infiltration experiment.

Techniques for CT and MR, post-processing, radiation.

Brain perfusion can be assessed by CT and MR. For CT, two major techniquesare used. First, Xenon CT is an equilibrium technique based on a freely diffusibletracer. First pass of iodinated contrast injected intravenously is a second method,more widely available. Both methods are proven to be robust and quantitative,thanks to the linear relationship between contrast concentration and x-ray attenuation.For the CT methods, concern regarding x-ray doses delivered to the patientsneed to be addressed. MR is also able to assess brain perfusion using the firstpass of gadolinium based contrast agent injected intravenously. This method hasto be considered as a semi-quantitative because of the non linear relationshipbetween contrast concentration and MR signal changes. Arterial spin labelingis another MR method assessing brain perfusion without injection of contrast. Insuch case, the blood flow in the carotids is magnetically labelled by an externalradiofrequency pulse and observed during its first pass through the brain. Eachof this various CT and MR techniques have advantages and limits that will be illustratedand summarised.Learning Objectives:1. To understand and compare the different techniques for brain perfusionimaging.2. To learn about the methods of acquisition and post-processing of brainperfusion by first pass of contrast agent for CT and MR.3. To learn about non contrast MR methods (arterial spin labelling).

Evolution of a polymineralic mantle shear zone and the role of second phases in the localization of deformation

The influence of second phases (e.g., pyroxenes) on olivine grain size was studied by quantitative microfabric analyses of samples of the Hilti massif mantle shear zone (Semail ophiolite, Oman). The microstructures range from porphyroclastic tectonites to ultramylonites, from outside to the center of the shear zone. Starting at conditions of ridge-related flow, they formed under continuous cooling leading to progressive strain localization. The dependence of the average olivine grain size on the second-phase content can be split into a second-phase controlled and a dynamic recrystallization-controlled field. In the former, the olivine grain size is related to the ratio between the second-phase grain size and volume fraction (Zener parameter). In the latter, dynamic recrystallization manifested by a balance between grain growth and grain size reduction processes yields a stable olivine grain size. In both fields the average olivine and second-phase grain size decreases with decreasing temperature. Combining the microstructural information with deformation mechanism maps suggests that the porphyroclastic tectonites (similar to 1100 degrees C) and mylonites (similar to 800 degrees C) formed under the predominance of dislocation creep. Since olivine-rich layers are intercalated with layer parallel, polymineralic bands in the mylonites, nearly equiviscous conditions can be assumed. In the ultramylonites, diffusion creep represents the major deformation mechanism in the polymineralic layers. It is this switch in deformation mechanism from dislocation creep to diffusion creep that forces strain to localize in the fine-grained polymineralic domains at low temperatures (<similar to 700 degrees C), underlining the role of the second phases on strain localization in cooling mantle rocks.