Specific targeting of the GABA-A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice

An imbalance between inhibitory and excitatory neurotransmission has been proposed to contribute to altered brain function in individuals with Down syndrome (DS). Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system and accordingly treatment with GABA-A antagonists can efficiently restore cognitive functions of Ts65Dn mice, a genetic model for DS. However, GABA-A antagonists are also convulsant which preclude their use for therapeutic intervention in DS individuals. Here, we have evaluated safer strategies to release GABAergic inhibition using a GABA-A-benzodiazepine receptor inverse agonist selective for the α5-subtype (α5IA). We demonstrate that α5IA restores learning and memory functions of Ts65Dn mice in the novel-object recognition and in the Morris water maze tasks. Furthermore, we show that following behavioural stimulation, α5IA enhances learning-evoked immediate early gene products in specific brain regions involved in cognition. Importantly, acute and chronic treatments with α5IA do not induce any convulsant or anxiogenic effects that are associated with GABA-A antagonists or non-selective inverse agonists of the GABA-A-benzodiazepine receptors. Finally, chronic treatment with α5IA did not induce histological alterations in the brain, liver and kidney of mice. Our results suggest that non-convulsant α5-selective GABA-A inverse agonists could improve learning and memory deficits in DS individuals

Background discrimination capabilities of a heat and ionization germanium cryogenic detector

The discrimination capabilities of a 70 g heat and ionization Ge bolometer are studied. This first prototype has been used by the EDELWEISS Dark Matter experiment, installed in the Laboratoire Souterrain de Modane, for direct detection of WIMPs. Gamma and neutron calibrations demonstrate that this type of detector is able to reject more than 99.6% of the background while retaining 95% of the signal, provided that the background events distribution is not biased towards the surface of the Ge crystal. However, the 1.17 kg.day of data taken in a relatively important radioactive environment show an extra population slightly overlapping the signal. This background is likely due to interactions of low energy photons or electrons near the surface of the crystal, and is somewhat reduced by applying a higher charge-collecting inverse bias voltage (-6 V instead of -2 V) to the Ge diode. Despite this contamination, more than 98% of the background can be rejected while retaining 50% of the signal. This yields a conservative upper limit of 0.7 event.day^{-1}.kg^{-1}.keV^{-1}_{recoil} at 90% confidence level in the 15-45 keV recoil energy interval; the present sensitivity appears to be limited by the fast ambient neutrons. Upgrades in progress on the installation are summarized.Comment: Submitted to Astroparticle Physics, 14 page

INSPEX: Make environment perception available as a portable system

International audienceObstacle avoidance systems for autonomous vehicles combine multiple sensing technologies (i.e. LiDAR, Radar, Ultrasound and Visual) to detect different types of obstacles across the full range of lighting and weather conditions. Sensor data are fused with vehicle orientation (obtained for instance from an Inertial Measurement Unit and/or compass) and navigation subsystems. Power hungry, they require powerful computational capability, which limits their use to high-end vehicles and robots. 2 INSPEX ambition The H2020 INSPEX project plans to make obstacle detection capabilities available as a personal portable multi-sensors, miniaturised, low power device. This device will detect, locate and warn of obstacles under different environmental conditions, in indoor/outdoor environments, with static and mobile obstacles. Potential applications range from safer human navigation in reduced visibility conditions (e.g. for first responders and fire brigades), small robot/drone obstacle avoidance systems to navigation for the visually and mobility impaired people. As primary demonstrator (Fig.1), we will plug the INSPEX device on a white cane (see Fig. 1) for Visually Impaired and Blind (VIB) people to detect obstacle over the whole person height, provide audio feedback about harmful obstacles, improve their mobility confidence and reduce injuries, especially at waist and head levels [1]. The device will offer a "safety cocoon" to its user

Towards a portable smart spatial exploration system for environment perception

International audienc

Tissue Clearing and Deep Imaging of the Kidney Using Confocal and Two-Photon Microscopy

Microscopic and macroscopic evaluation of biological tissues in three dimensions is becoming increasingly popular. This trend is coincident with the emergence of numerous tissue clearing strategies, and advancements in confocal and two-photon microscopy, enabling the study of intact organs and systems down to cellular and sub-cellular resolution. In this chapter, we describe a wholemount immunofluorescence technique for labeling structures in renal tissue. This technique combined with solvent-based tissue clearing and confocal imaging, with or without two-photon excitation, provides greater structural information than traditional sectioning and staining alone. Given the addition of paraffin embedding to our method, this hybrid protocol offers a powerful approach to combine confocal or two-photon findings with histological and further immunofluorescent analysis within the same tissue

Transformation and analysis of tobacco plant var Petit havana with T-urf13 gene under anther-specific TA29 promoter

T-urf13, a well-documented cms-associated gene from maize, has been shown to render methomyl sensitivity to heterologous systems like rice, yeast and bacteria when expressed constitutively. Since these transgenic plants were fertile, it was hypothesized that T-urf13 gene if expressed in anthers may result in male sterility that could be used for hybrid seed production. Hence, this work was aimed at analysing whether T-urf13 gene when expressed in anthers can result in male sterile plants or requires methomyl treatment to cause male sterility (controllable). This is the first report of transformation of tobacco with T-urf13 gene under anther-specific promoter (TA29) with or without mitochondrial targeting sequence. Most of the transgenic plants obtained were fertile; this was surprising as many male sterile plants were expected as T-urf13 gene is a cms associated gene. Our results suggest that it may not be possible to obtain male sterility by expressing URF13 in the anther by itself or by methomyl application

INSPEX: design and integration of a portable/wearable smart spatial exploration system

The INSPEX H2020 project main objective is to integrate automotive-equivalent spatial exploration and obstacle detection functionalities into a portable/wearable multi-sensor, miniaturised, low power device. The INSPEX system will detect and localise in real-time static and mobile obstacles under various environmental conditions in 3D. Potential applications range from safer human navigation in reduced visibility, small robot/drone obstacle avoidance systems to navigation for the visually/mobility impaired, this latter being the primary use-case considered in the project

Objective comparison of particle tracking methods

Particle tracking is of key importance for quantitative analysis of intracellular dynamic processes from time-lapse microscopy image data. Because manually detecting and following large numbers of individual particles is not feasible, automated computational methods have been developed for these tasks by many groups. Aiming to perform an objective comparison of methods, we gathered the community and organized an open competition in which participating teams applied their own methods independently to a commonly defined data set including diverse scenarios. Performance was assessed using commonly defined measures. Although no single method performed best across all scenarios, the results revealed clear differences between the various approaches, leading to notable practical conclusions for users and developers

PhagoSight: an open-source MATLAB® package for the analysis of fluorescent neutrophil and macrophage migration in a zebrafish model

Neutrophil migration in zebrafish larvae is increasingly used as a model to study the response of these leukocytes to different determinants of the cellular inflammatory response. However, it remains challenging to extract comprehensive information describing the behaviour of neutrophils from the multi-dimensional data sets acquired with widefield or confocal microscopes. Here, we describe PhagoSight, an open-source software package for the segmentation, tracking and visualisation of migrating phagocytes in three dimensions. The algorithms in PhagoSight extract a large number of measurements that summarise the behaviour of neutrophils, but that could potentially be applied to any moving fluorescent cells. To derive a useful panel of variables quantifying aspects of neutrophil migratory behaviour, and to demonstrate the utility of PhagoSight, we evaluated changes in the volume of migrating neutrophils. Cell volume increased as neutrophils migrated towards the wound region of injured zebrafish. PhagoSight is openly available as MATLAB® m-files under the GNU General Public License. Synthetic data sets and a comprehensive user manual are available from http://www.phagosight.org