Development of the PETAL Laser Facility and its Diagnostic Tools

The PETAL system (PETawatt Aquitaine Laser) is a high-energy short-pulse laser, currently in an advanced construction phase, to be combined with the French Mega-Joule Laser (LMJ). In a first operational phase (beginning in 2015 and 2016) PETAL will provide 1 kJ in 1 ps and will be coupled to the first four LMJ quads. The ultimate performance goal to reach 7PW (3.5 kJ with 0.5 ps pulses). Once in operation, LMJ and PETAL will form a unique facility in Europe for High Energy Density Physics (HEDP). PETAL is aiming at providing secondary sources of particles and radiation to diagnose the HED plasmas generated by the LMJ beams. It also will be used to create HED states by short-pulse heating of matter. Petal+ is an auxiliary project addressed to design and build diagnostics for experiments with PETAL. Within this project, three types of diagnostics are planned: a proton spectrometer, an electronspectrometer and a large-range X-ray spectrometer

Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets

The mammalian precerebellar pontine nucleus (PN) has a main role in relaying cortical information to the cerebellum. The molecular determinants establishing ordered connectivity patterns between cortical afferents and precerebellar neurons are largely unknown. We show that expression of Hox5 transcription factors is induced in specific subsets of postmitotic PN neurons at migration onset. Hox5 induction is achieved by response to retinoic acid signaling, resulting in Jmjd3-dependent derepression of Polycomb chromatin and 3D conformational changes. Hoxa5 drives neurons to settle posteriorly in the PN, where they are monosynaptically targeted by cortical neuron subsets mainly carrying limb somatosensation. Furthermore, Hoxa5 postmigratory ectopic expression in PN neurons is sufficient to attract cortical somatosensory inputs regardless of position and avoid visual afferents. Transcriptome analysis further suggests that Hoxa5 is involved in circuit formation. Thus, Hoxa5 coordinates postmitotic specification, migration, settling position, and subcircuit assembly of PN neuron subsets in the cortico-cerebellar pathway.Peer reviewe

A unique bipartite Polycomb signature regulates stimulus-response transcription during development

Rapid cellular responses to environmental stimuli are fundamental for development and maturation. Immediate early genes can be transcriptionally induced within minutes in response to a variety of signals. How their induction levels are regulated and their untimely activation by spurious signals prevented during development is poorly understood. We found that in developing sensory neurons, before perinatal sensory-activity-dependent induction, immediate early genes are embedded into a unique bipartite Polycomb chromatin signature, carrying active H3K27ac on promoters but repressive Ezh2-dependent H3K27me3 on gene bodies. This bipartite signature is widely present in developing cell types, including embryonic stem cells. Polycomb marking of gene bodies inhibits mRNA elongation, dampening productive transcription, while still allowing for fast stimulus-dependent mark removal and bipartite gene induction. We reveal a developmental epigenetic mechanism regulating the rapidity and amplitude of the transcriptional response to relevant stimuli, while preventing inappropriate activation of stimulus-response genes.T.K. was supported by a Japan Society for the Promotion of Science fellowship, and O.J. was supported by an EMBO Long-Term fellowship. F.M.R. was supported by the Swiss National Science Foundation (31003A_149573 and 31003A_175776). This project has also received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant no. 810111-EpiCrest2Reg). F.M.R. and M.B.S. were also supported by the Novartis Research Foundation.Peer reviewe

Prenatal thalamic waves regulate cortical area size prior to sensory processing

The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice. This mechanism is mediated by spontaneous thalamic calcium waves that propagate among sensory-modality thalamic nuclei up to the cortex and that provide a means of communication among sensory systems. Wave pattern alterations in one nucleus lead to changes in the pattern of the remaining ones, triggering changes in thalamic gene expression and cortical area size. Thus, silencing calcium waves in the auditory thalamus induces Rorβ upregulation in a neighbouring somatosensory nucleus preluding the enlargement of the barrel-field. These findings reveal that embryonic thalamic calcium waves coordinate cortical sensory area patterning and plasticity prior to sensory information processing.V.M.-J. holds a ‘Severo Ochoa’ PhD fellowship and N.A.-B. a FPI fellowship, both from the MINECO. C.M. held a JAE-Predoc fellowship from the CSIC, and H.G. held postdoctoral fellowships from the Swedish Research council and Brain Foundation. Supported by the Swiss National Science Foundation (31003A_149573) and the Novartis Research Foundation to F.M.R., the JSPS KAKENHI (JP16H06459) to T.I. and by the Spanish MINECO BFU2012-34298 and BFU2015-64432-R, and two European Commission Grants ERC-2009-StG-20081210 and ERC-2014-CoG-647012 to G.L.-B. G.L.-B. is an EMBO YIP Investigator and a FENS-Kavli scholar.Peer reviewe

Hox Paralog Group 2 Genes Control the Migration of Mouse Pontine Neurons through Slit-Robo Signaling

The pontine neurons (PN) represent a major source of mossy fiber projections to the cerebellum. During mouse hindbrain development, PN migrate tangentially and sequentially along both the anteroposterior (AP) and dorsoventral (DV) axes. Unlike DV migration, which is controlled by the Netrin-1/Dcc attractive pathway, little is known about the molecular mechanisms guiding PN migration along the AP axis. Here, we show that Hoxa2 and Hoxb2 are required both intrinsically and extrinsically to maintain normal AP migration of subsets of PN, by preventing their premature ventral attraction towards the midline. Moreover, the migration defects observed in Hoxa2 and Hoxb2 mutant mice were phenocopied in compound Robo1;Robo2, Slit1;Slit2, and Robo2;Slit2 knockout animals, indicating that these guidance molecules act downstream of Hox genes to control PN migration. Indeed, using chromatin immunoprecipitation assays, we further demonstrated that Robo2 is a direct target of Hoxa2 in vivo and that maintenance of high Robo and Slit expression levels was impaired in Hoxa2 mutant mice. Lastly, the analysis of Phox2b-deficient mice indicated that the facial motor nucleus is a major Slit signaling source required to prevent premature ventral migration of PN. These findings provide novel insights into the molecular control of neuronal migration from transcription factor to regulation of guidance receptor and ligand expression. Specifically, they address the question of how exposure to multiple guidance cues along the AP and DV axes is regulated at the transcriptional level and in turn translated into stereotyped migratory responses during tangential migration of neurons in the developing mammalian brain

Euclid Near Infrared Spectrometer and Photometer instrument concept and first test results obtained for different breadboards models at the end of phase C

The Euclid mission objective is to understand why the expansion of the Universe is accelerating through by mapping the geometry of the dark Universe by investigating the distance-redshift relationship and tracing the evolution of cosmic structures. The Euclid project is part of ESA's Cosmic Vision program with its launch planned for 2020 (ref [1]). The NISP (Near Infrared Spectrometer and Photometer) is one of the two Euclid instruments and is operating in the near-IR spectral region (900- 2000nm) as a photometer and spectrometer. The instrument is composed of: - a cold (135K) optomechanical subsystem consisting of a Silicon carbide structure, an optical assembly (corrector and camera lens), a filter wheel mechanism, a grism wheel mechanism, a calibration unit and a thermal control system - a detection subsystem based on a mosaic of 16 HAWAII2RG cooled to 95K with their front-end readout electronic cooled to 140K, integrated on a mechanical focal plane structure made with molybdenum and aluminum. The detection subsystem is mounted on the optomechanical subsystem structure - a warm electronic subsystem (280K) composed of a data processing / detector control unit and of an instrument control unit that interfaces with the spacecraft via a 1553 bus for command and control and via Spacewire links for science data This presentation describes the architecture of the instrument at the end of the phase C (Detailed Design Review), the expected performance, the technological key challenges and preliminary test results obtained for different NISP subsystem breadboards and for the NISP Structural and Thermal model (STM)

Decision Support for Removing Fractured Endodontic Instruments: A Patient-Specific Approach

International audienceAim: instrumental fracture is a common endodontic complication that is treated by surgical or non-surgical removal approaches. However, no tool exists to help the clinician to choose between available strategies, and decision-making is mostly based on clinical judgment. Digital solutions, such as Finite Element Analysis (FEA) and Virtual Treatment Planning (VTP), were recently proposed in maxillofacial surgery to help in this regard. The aim of the present paper is to present a digital tool to choose between non-surgical and surgical strategies in a clinical situation of fractured instrument (FI).Material and methods: patient tooth data were recorded using cone beam computed tomography (CBCT). VTP was conducted using an application suited for medical images to segment and plan the procedure. FEA has been carried out using the Abaqus software according to published material properties. Five models have been created: the initial state of the patient, two non-surgical removal strategies using a low or high root canal enlargement, and two surgical removal strategies using a 3-or 6-mm apicoectomy.Resuls: Results of the VTP found a risk of perforation for the non-surgical strategies and a sinus proximity for surgical ones. FEA identified the lowest mechanical risk for the 3-mm apicoectomy strategy. A 3-mm apicoectomy approach was finally chosen and performed.Conclusion: this digital approach could offer a decision tool for the instrument removal by planning the treatment and predicting the mechanical impact of each strategy

Development of the PETAL Laser Facility and its Diagnostic Tools

The PETAL system (PETawatt Aquitaine Laser) is a high-energy short-pulse laser, currently in an advanced construction phase, to be combined with the French Mega-Joule Laser (LMJ). In a first operational phase (beginning in 2015 and 2016) PETAL will provide 1 kJ in 1 ps and will be coupled to the first four LMJ quads. The ultimate performance goal to reach 7PW (3.5 kJ with 0.5 ps pulses). Once in operation, LMJ and PETAL will form a unique facility in Europe for High Energy Density Physics (HEDP). PETAL is aiming at providing secondary sources of particles and radiation to diagnose the HED plasmas generated by the LMJ beams. It also will be used to create HED states by short-pulse heating of matter. Petal+ is an auxiliary project addressed to design and build diagnostics for experiments with PETAL. Within this project, three types of diagnostics are planned: a proton spectrometer, an electronspectrometer and a large-range X-ray spectrometer

Transient Receptor Potential Vanilloid 4 channel participates in mouse ventricular electrical activity

International audienc