Phenotypic characterisation of a novel mutant mouse with target deletion of dysbindin-1A in relation to the schizophrenia risk gent DTNBP1.

DTNBPl (dystrobrevin-binding protein-1) has been strongly identified as a susceptibility gene for schizophrenia and implicated in cognitive function. Downregulation of DTNBPl expression in dorsolateral prefrontal cortex (DLPFC) and hippocampal formation (HF) of patients with schizophrenia may represent a primary pathophysiological mechanism. Described as a \u27hub\u27, dysbindin associates into multiple complexes in the brain and exerts a wide variety o f functions implicated in early brain development and neuroplasticity. The expression pattern o f the different dysbindin isoforms varies with brain development, tissue areas and subcellular localisations, and may interact with different partners. Variations in DTNBPl more specifically associated with dysbindin-1A may contribute to early-onset and cognitive deficits. Dysbindin-fA, the full-length isoform, is primarily expressed during embryonic and early postnatal development in postsynaptic areas. Comparatively to sandy mutant mouse models, expressing no dysbindin proteins, phenotypic characterisation of dysbindin-1A knockout (KO) mice, on a C57BL/6J background, will help to clarify the function o f DTNBPl in schizophrenia. As constructed by GlaxoSmithKline (GSK), this mutant line shows sex-specific deficits, with female KO being more reactive to stressful situations and male KO showing hyperactivity on initial exposures to a novel environment that maybe related to some disruption to habituation and dysregulation o f DG-dependent working memory function (pattern separation). For both sexes these phenotypes occur concurrently with normal general physiological indices, sensori-motor gating, social behaviours, delay-independent working memory and attention, long-term memory and delaydependent working memory. Further investigations in the conditional floxed mutant, also constructed by GSK, may help to clarify the neural mechanisms underlying these features that implicate dysbindin-lA in schizophrenia-re la ted cognitive processes and stress reactivity

Réactivité de polyphénols du vin sous conditions oxydantes (hémisynthèse des mongolicaïnes, et d'adduits entre polyphénols et thiols odorants)

Le vin est un milieu complexe qui évolue tout au long des étapes devinification. Pour mieux appréhender ses qualités et ses défauts, de nombreuses équipesde recherche s intéressent à la compréhension de la chimie du vin. Dans ce contexte, lesujet de ce mémoire concerne l étude de l évolution chimique de certaines moléculespolyphénoliques du vin sous conditions oxydantes et/ou acides, afin d isoler et decaractériser de nouveaux composés susceptibles de se former dans le vin. Deux aspectssont examinés. Le premier concerne l oxydation de deux flavano ellagitannins, lesacutissimines A et B, formées à partir d un monomère de tannins condensés, lacatéchine, et d un ellagitannin C glucosidique, la vescalagine, extraite du bois de chênepar le vin lors de l élevage en barrique. Cette étude a permis d isoler les mongolicaïnes Aet B et deux analogues du camelliatannin G et de mettre en évidence leur formation parun mécanisme d autoxydation. Le deuxième aspect concerne l évaluation desconséquences de la présence de certains polyphénols dans le vin sur les composésthiolés odorants. Leur comportement et leur réactivité chimiques sont décrits dans desmilieux différents, avec l hémisynthèse de thio ellagitannins sous conditions acides, et laformation d adduits thio catéchols et thio pyrogallols sous conditions oxydantes,transformations chimiques pouvant occasionner la perte des odeurs et arômes du vindus aux composés thiolés odorants.The wine is a complex medium that evolves throughout the different stages ofthe wine making process. To understand both the qualities and defects of wine,numerous research team worldwide investigate the chemistry of wine. In this context,the subject of this thesis concerns the study of the chemical evolution of some winepolyphenolic molecules under oxidizing and/or acidic conditions in the aim of isolatingand characterizing new compounds likely formed in wine. Two aspects are examined.The first one is the study of the oxidation of two flavano ellagitannins, acutissimins Aand B, formed from a monomer of condensed tannins, catechin, and a C glucosidicellagitannin, vescalagin, extracted from oak wood by the wine solution during its agingin barrels. This study led to the isolation of mongolicains A and B and two analogues ofcamelliatannin G, and revealed their formation according to an autoxydationmechanism. The second aspect of this work concerns the consequences of the presencein wine of some polyphenols on wine odorous thiols. Their chemical behavior andreactivity are described in different media, with the hemisynthesis of thio ellagitanninsunder acidic conditions, and the formation of thio catechol and thio pyrogallol adductsunder oxidizing conditions, chemical transformations that could explain the loss ofodors and aromas due to wine odorous thiols.BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

Evidence of trophic transfer of microcystins from the gastropod Lymnaea stagnalis to the fish Gasterosteus aculeatus.

International audienceAccording to our previous results the gastropod Lymnaea stagnalis exposed to MC-producing cyanobacteria accumulates microcystins (MCs) both as free and covalently bound forms in its tissues, therefore representing a potential risk of MC transfer through the food web. This study demonstrates in a laboratory experiment the transfer of free and bound MCs from L. stagnalis intoxicated by MC-producing Planktothrix agardhii ingestion to the fish Gasterosteus aculeatus. Fish were fed during five days with digestive glands of L. stagnalis containing various concentrations of free and bound MCs, then with toxin-free digestive glands during a 5-day depuration period. MC accumulation was measured in gastropod digestive gland and in various fish organs (liver, muscle, kidney, and gills). The impact on fish was evaluated through detoxification enzyme (glutathion-S-transferase, glutathion peroxydase and superoxyde dismutase) activities, hepatic histopathology, and modifications in gill ventilation, feeding and locomotion. G. aculeatus ingestion rate was similar with intoxicated and toxin-free diet. Fish accumulated MCs (up to 3.96 ± 0.14 μg g−1 DW) in all organs and in decreasing order in liver, muscle, kidney and gills. Hepatic histopathology was moderate. Glutathion peroxydase was activated in gills during intoxication suggesting a slight reactive oxygen species production, but without any impact on gill ventilation. Intoxication via ingestion of MC-intoxicated snails impacted fish locomotion. Intoxicated fish remained significantly less mobile than controls during the intoxication period possibly due to a lower health condition, whereas they showed a greater mobility during the depuration period that might be related to an acute foraging for food. During depuration, MC elimination was total in gills and kidney, but partial in liver and muscle. Our results assess the MC transfer from gastropods to fish and the potential risk induced by bound MCs in the food web

Two-dimensional ultrasonic computed tomography of growth bone

International audienceUltrasonography is the main first-line imaging technique used to diagnose various pediatric pathologies. Pediatric radiologists are very keen on ultrasonography since it is a non-invasive, non-irradiant, painless, inexpensive imaging modality, which is also practicable on bedside. In bone diseases, this technique has also proved to be a very effective tool to assess congenital (i.e., hip dysphasia), infectious (i.e., sub-periostal abscess), inflammatory (i.e., chronic arthritis), and even traumatic (i.e., ankle sprain) processes. However, with standard devices, this exam is not suitable for diagnosis or monitoring bone tumors, classically explored by other more effective techniques, which presented various disadvantages (cost, irradiation, sedation, accessibility). Many authors have dealt with the ultrasonic imaging of bones. Their main aim has usually been to assess the thickness of the diaphysis and to calculate the speed of sound of a wave crossing the structure. Our group has been focusing on the cross-sectional radial imaging process, using ultrasonic computed tomography. Known to be a potentially valuable method of imaging objects with a similar acoustical impedance, difficulties arise when it is proposed to obtain quantitative tomograms of more highly contrasted media (hard bone tissues). Finding solutions here involves either using non-linear schemes and/or performing extensive studies on the limitation of the initial approximation. In this paper, we recall the limits of the ultrasonic computed tomography when dealing with highly contrasted scatterers, using a high-order tomographic method. The performances and limitations are evaluated in the basis of simulated and experimental data, obtained using an ultrasonic scanner, to one geometrical-mimicking phantom and to a real children fibula. Sample thicknesses and speed-of-sound varied as a function of radial position and the experimental procedure fulfilled the criteria of the diffraction tomography. Results are promising and suggest that the geometrical and acoustical characteristics of the bones, which are known to be one of the main factors contributing to the growth bone disease, can be determined using this ultrasonic computed tomography

Effects of Age and Task Load on Drivers’ Response Accuracy and Reaction Time When Responding to Traffic Lights

International audienceDue to population aging, elderly drivers represent an increasing proportion of car drivers. Yet, how aging alters sensorimotor functions and impacts driving safety remains poorly understood. This paper aimed at assessing to which extent elderly drivers are sensitive to various task loads and how this affects the reaction time (RT) in a driving context. Old and middle-aged people completed RT tasks which reproduced cognitive demands encountered while driving. Participants had to detect and respond to traffic lights or traffic light arrows as quickly as possible, under three experimental conditions of incremental difficulty. In both groups, we hypothesized that decision-making would be impacted by the number of cues to be processed. The first test was a simple measure of RT. The second and third tests were choice RT tasks requiring the processing of 3 and 5 cues, respectively. Responses were collected within a 2 s time-window. Otherwise, the trial was considered a no-response. In both groups, the data revealed that RT, error rate (incorrect answers), and no-response rate increased along with task difficulty. However, the middle-aged group outperformed the elderly group. The RT difference between the two groups increased drastically along with task difficulty. In the third test, the rate of no-response suggested that elderly drivers needed more than 2 s to process complex information and respond accurately. Both prolonged RT and increased no-response rate, especially for difficult tasks, might attest an impairment of cognitive abilities in relation to aging. Accordingly, casual driving conditions for young drivers may be particularly complex and stressful for elderly people who should thus be informed about the effects of normal aging upon driving

A three-thousand-year history of vegetation and human impact in Burgundy (France) reconstructed from pollen and non-pollen palynomophs analysis

International audienceThis article presents a 241 cm long sediment record documenting the vegetation history using previous termpollen and non-pollennext term palynomorphs recovered from the Fénay marsh in Burgundy (Dijon area – previous termFrance). The pollen and non-pollennext term palynomorphs (NPP) record largely reflects intensive human influence (clearing, cultivation and grazing) on the surrounding area from the Late Bronze Age and Hallstatt period. La Tène period is marked by drier conditions and a substantial increase in Alnus. During the Gallo-Roman period, high values of Alnus decrease to the benefit of Quercus. In the Early Middle Ages (5th–10th C), the swamp becomes a temporary pond and Cerealia type and Secale are cultivated in this very open landscape. During the Late Middle Ages (13th–15th C), the temporary pond is transformed into a larger and deeper pond, used by the Cistercians for hydraulic power and perhaps as a hemp-retting pit. By the end of the 16th C, the pond had dried out and was used for the cultivation of cereal

PD1/PD-L1 dependent immunosuppression by huiPS-derived cell population

Poster presentationInternational audienc

Far-Infrared detection of neutral atomic oxygen toward the Horsehead Nebula

We present the first detection of neutral atomic oxygen (3P_1-3P_2 fine structure line at ~63um) toward the Horsehead photodissociation region (PDR). The cloud has been mapped with the Spitzer Space Telescope at far-IR (FIR) wavelengths using MIPS in the spectral energy distribution (SED) mode. The [OI]63um line peaks at the illuminated edge of the cloud at AV~0.1-0.5 (inward the gas becomes too cold and outward the gas density drops). The luminosity carried by the [OI]63um line represents a significant fraction of the total FIR dust luminosity (I_63/I_FIR~4x10^-3). We analyze the dust continuum emission and the nonlocal OI excitation and radiative transfer in detail. The observations are reproduced with a gas density of n_H~10^4 cm^-3 and gas and dust temperatures of T_k~100 K and T_d~30 K. We conclude that the determination of the OI 3P_J level populations and emergent line intensities at such ``low'' densities is a complex non-LTE problem. FIR radiative pumping, [OI]63um subthermal emission, [OI]145um suprathermal and even maser emission can occur and decrease the resulting [OI]63/145 intensity ratio. The Herschel Space Observatory, observing from ~55 to 672um, will allow us to exploit the diagnostic power of FIR fine structure lines with unprecedented resolution and sensitivity.Comment: Accepted for publication in ApJ Letters (editorial corrections included

Humid Evolution of Haze in the Atmosphere of Super-Earths in the Habitable Zone

Photochemical hazes are expected to form and significantly contribute to the chemical and radiative balance of exoplanets with relatively moderate temperatures, possibly in the habitable zone of their host star. In the presence of humidity, haze particles might thus serve as cloud condensation nuclei and trigger the formation of water droplets. In the present work, we are interested in the chemical impact of such a close interaction between photochemical hazes and humidity on the organic content composing the hazes and on the capacity to generate organic molecules with high prebiotic potential. For this purpose, we explore experimentally the sweet spot by combining N-dominated super-Earth exoplanets in agreement with Titan's rich organic photochemistry and humid conditions expected for exoplanets in habitable zones. A logarithmic increase with time is observed for the relative abundance of oxygenated species, with O-containing molecules dominating after 1 month only. The rapidity of the process suggests that the humid evolution of N-rich organic haze provides an efficient source of molecules with high prebiotic potential