Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy

International audienceMyotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Expérience Némo3 : étude de la stabilité des étalonnages en énergie et en temps du calorimètre. Mesure de la contribution des neutrons au bruit de fond de la double désintégration Beta et sans émission de neutrino.

La mise en évidence de la décroissance double bêta sans émission de neutrino (bb0n), interdite par le Modèle Standard, permettrait de déterminer si le neutrino est une particule massive de Majorana. Pour cela, la collaboration NEMO a construit le détecteur NEMO3 qui sera sensible à une masse effective du neutrino d'environ 0,2 eV. Il est constitué d'une source émettrice bb, d'une chambre à fils et d'un calorimètre formé de 1940 compteurs à scintillation permettant de mesurer l'énergie et le temps de vol des électrons. Pour une masse de 0,2 eV, le signal bb0n correspondrait à la détection de quelques événements par an. Pour le mesurer, il est indispensable de connaître avec précision les étalonnages en énergie et en temps du calorimètre et de maîtriser toutes les sources de bruit de fond. La première partie de ce travail a consisté en l'étude du suivi quotidien des étalonnages du calorimètre par un système d'étalonnage relatif utilisant une lumière laser. Un programme permettant l'automatisation de l'étude des spectres laser et le calcul des coefficients de correction des étalonnages a été mis au point. Le comportement de l'ensemble du calorimètre a ainsi pu être caractérisé sur une durée de 23 jours. La deuxième partie de ce travail a porté sur l'étude de la contribution des neutrons et du rayonnement g au bruit de fond de l'expérience. Les prises de données avec et sans le blindage de fer, avec et sans source de neutrons ont systématiquement été comparées avec les simulations. Le très bon accord entre l'expérience et les simulations nous a permis de conclure qu'avec les blindages g et neutron et le champ magnétique, l'objectif fixé de 0 événement de bruit de fond d'origine externe à la source bb sera atteint.The discovery of neutrinoless double beta decay (bb0n), forbidden in the Standard Theory, would permit to determine if neutrinos are massive Majorana particules. With this aim, the NEMO collaboration has built the NEMO3 detector with a sensitivity of 0,2 eV on the neutrino effective mass. This detector is composed of a bb emitter source, a wire chamber and a calorimeter made of 1940 scintillation counters in order to measure the energy and time of flight of the electrons. The bb0n signal expected is a few events per year. To measure it, it is essential to have a precise knowledge of the calorimeter energy and time calibration, and to master all the backround sources. The first part of this work was dedicated to the study of the daily calibration survey with the help of a relative calibration system based on laser light. An automatized program for laser spectra study and calculation of calibration corrections has been achieved. The behaviour of the whole calorimeter has been characterized for a 23 days period. The second part of this work was the study of the neutrons and g ray contribution to the background of the experiment. The data takingwith and without iron shielding,with and without neutron source were systematically compared with simulations. The very good agreement between experiment and simulations allows us to conclude that with g and neutron shieldings together with a magnetic field, the objective of 0 external background event will be reached

A new neutrinoless double beta decay experiment: R2D2

The search for neutrinoless double beta decay could cast light on one critical piece missing in our knowledge i.e. the nature of the neutrino mass. Its observation is indeed the most sensitive experimental way to prove that neutrino is a Majorana particle. The observation of such a potentially rare process demands a detector with an excellent energy resolution, an extremely low radioactivity and a large mass of emitter isotope. Nowadays many techniques are pursued but none of them meets all the requirements at the same time. The goal of R2D2 is to prove that a spherical high pressure TPC could meet all the requirements and provide an ideal detector for the 0vββ decay search. In the presented talk the R2D2 goal and preliminary results are presented as well as the project roadmap

Reactor experiments review

International audienceReactors are a copious source of anti-neutrinos and for this reason they have been critical tools to pin down neutrino fundamental properties since their discovery. Depending on the distance between reactor cores and experiments different oscillation parameter regions can be probed: in this review the regimes of very short, short and medium baselines are discussed with highlights on the current results and prospectives. Furthermore the high resolution which can be nowadays achieved allows to understand better the contributions from different fissile elements in the anti-neutrino spectrum. Fuel composition analysis as well as sterile neutrino search are also discussed

9^9Li and 8^8He decays in GEANT4

The decays of cosmogenic nuclei such as 9 Li and 8 He represent one of the largest irreducible backgrounds for reactor antineutrino experiments. The correct treatment of such decays are of fundamental importance in the study of cosmogenic backgrounds and in their rejection, hence the full chain of intermediate excited states must be accounted for. Currently the treatment in GEANT4 of the modelling of de-excitation of 9 Be and 8 Li, which are the daughter nuclei of 9 Li and 8 He respectively, is not correct. 9 Be excited states should break into a neutron and two α ’s, and 8 Li excited states should emit a neutron and possibly an α and a triton depending on the decay chain, whereas in GEANT4 they both reach the ground state by emitting a gamma. Based on the available nuclear measurements we included the correct treatment of 9 Li and 8 He decays in GEANT4 and compared the obtained results with the spectra published by the Double Chooz collaboration finding an excellent agreement

Expérience NEMO3 (Étude de la stabilité des étalonnages en énergie et en temps du calorimètre)

La mise en évidence de la décroissance double bêta sans émission de neutrino (bb0n), interdite par le Modèle Standard, permettrait de déterminer si le neutrino est une particule massive de Majorana (v=v ). Pour cela, la collaboration NEMO a construit le détecteur NEMO3 qui sera sensible à une masse effective du neutrino d'environ 0,2 eV. Il est constitué d'une source émettrice bb, d'une chambre à fils et d'un calorimètre formé de 1940 compteurs à scintillation permettant de mesurer l'énergie et le temps de vol des électrons. Pour une masse de 0,2 eV, le signal bb0v correspondrait à la détection de quelques événements par an. Pour le mesurer, il est indispensable de connaître avec précision les étalonnages en énergie et en temps du calorimètre et de maîtriser toutes les sources de bruit de fond. La première partie de ce travail a consisté en l'étude du suivi quotidien des étalonnages du calorimètre par un système d'étalonnage relatif utilisant une lumière laser. Un programme permettant l'automatisation de l'étude des spectres laser et le calcul des coefficients de correction des étalonnages a été mis au point. Le comportement de l'ensemble du calorimètre a ainsi pu être caractérisé sur une durée de 23 jours. La deuxième partie de ce travail a porté sur l'étude de la contribution des neutrons et du rayonnement g au bruit de fond de l'expérience. Les prises de données avec et sans le blindage de fer, avec et sans source de neutrons ont systématiquement été comparées avec les simulations. Le très bon accord entre l'expérience et les simulations nous a permis de conclure qu'avec les blindages g et neutron et le champ magnétique, l'objectif fixé de 0 événement de bruit de fond d'origine externe à la source bb sera atteint.BORDEAUX1-BU Sciences-Talence (335222101) / SudocSTRASBOURG-Bib.Central Recherche (674822133) / SudocSudocFranceF

Simultaneous scintillation light and charge readout of a pure argon filled Spherical Proportional Counter

The possible use of a Spherical Proportional Counter for the search of neutrinoless double beta decay is investigated in the R2D2 R&D project. Dual charge and scintillation light readout may improve the detector performance. Tests were carried out with pure argon at 1.1 bar using a 6 × 6 mm2 silicon photomultiplier. Scintillation light was used for the first time to trigger in a spherical proportional counter. The measured drift time is in excellent agreement with the expectations from simulations. Furthermore the light signal emitted during the avalanche development exhibits features that could be exploited for event characterization

R2D2 spherical TPC: first energy resolution results

Spherical gaseous time projection chamber detectors, known also as spherical proportional counters, are widely used today for the search of rare phenomena such as weakly interacting massive particles. In principle such a detector exhibits a number of essential features for the search of neutrinoless double beta decay (ββ0ν). A ton scale experiment using a spherical gaseous time projection chamber could cover a region of parameter space relevant for the inverted mass hierarchy in just a few years of data taking. In this context, the first point to be addressed, and the major goal of the R2D2 R&D effort, is the energy resolution. The first results of the prototype, filled with argon at pressures varying from 0.2 to 1.1 bar, yielded an energy resolution as good as 1.1% FWHM for 5.3 MeV α tracks having ranges from 3 to 15 cm. This is a milestone that paves the way for further studies with xenon gas, and the possible use of this technology for ββ0ν searches