Overexpression of the Mitochondrial T3 Receptor p43 Induces a Shift in Skeletal Muscle Fiber Types

In previous studies, we have characterized a new hormonal pathway involving a mitochondrial T3 receptor (p43) acting as a mitochondrial transcription factor and consequently stimulating mitochondrial activity and mitochondrial biogenesis. We have established the involvement of this T3 pathway in the regulation of in vitro myoblast differentiation.We have generated mice overexpressing p43 under control of the human α-skeletal actin promoter. In agreement with the previous characterization of this promoter, northern-blot and western-blot experiments confirmed that after birth p43 was specifically overexpressed in skeletal muscle. As expected from in vitro studies, in 2-month old mice, p43 overexpression increased mitochondrial genes expression and mitochondrial biogenesis as attested by the increase of mitochondrial mass and mt-DNA copy number. In addition, transgenic mice had a body temperature 0.8°C higher than control ones and displayed lower plasma triiodothyronine levels. Skeletal muscles of transgenic mice were redder than wild-type animals suggesting an increased oxidative metabolism. In line with this observation, in gastrocnemius, we recorded a strong increase in cytochrome oxidase activity and in mitochondrial respiration. Moreover, we observed that p43 drives the formation of oxidative fibers: in soleus muscle, where MyHC IIa fibers were partly replaced by type I fibers; in gastrocnemius muscle, we found an increase in MyHC IIa and IIx expression associated with a reduction in the number of glycolytic fibers type IIb. In addition, we found that PGC-1α and PPARδ, two major regulators of muscle phenotype were up regulated in p43 transgenic mice suggesting that these proteins could be downstream targets of mitochondrial activity. These data indicate that the direct mitochondrial T3 pathway is deeply involved in the acquisition of contractile and metabolic features of muscle fibers in particular by regulating PGC-1α and PPARδ

Towards a test of the weak equivalence principle of gravity using anti-hydrogen at CERN

International audienceThe aim of the GBAR (Gravitational Behavior of Antimatter at Rest) experiment is to measure the free fall acceleration of an antihydrogen atom, in the terrestrial gravitational field at CERN and therefore test the Weak Equivalence Principle with antimatter. The aim is to measure the local gravity with a 1% uncertainty which can be reduced to few parts of 10-3

Sympathetic cooling of positrons to cryogenic temperatures for antihydrogen production

The positron, the antiparticle of the electron, predicted by Dirac in 1931 and discovered by Anderson in 1933, plays a key role in many scientific and everyday endeavours. Notably, the positron is a constituent of antihydrogen, the only long-lived neutral antimatter bound state that can currently be synthesized at low energy, presenting a prominent system for testing fundamental symmetries with high precision. Here, we report on the use of laser cooled Be+ ions to sympathetically cool a large and dense plasma of positrons to directly measured temperatures below 7 K in a Penning trap for antihydrogen synthesis. This will likely herald a significant increase in the amount of antihydrogen available for experimentation, thus facilitating further improvements in studies of fundamental symmetries

Design and Performance of a Novel Low Energy Multi-Species Beamline for the ALPHA Antihydrogen Experiment

The ALPHA Collaboration, based at the CERN Antiproton Decelerator, has recently implemented a novel beamline for low-energy ($\lesssim$ 100 eV) positron and antiproton transport between cylindrical Penning traps that have strong axial magnetic fields. Here, we describe how a combination of semianalytical and numerical calculations were used to optimise the layout and design of this beamline. Using experimental measurements taken during the initial commissioning of the instrument, we evaluate its performance and validate the models used for its development. By combining data from a range of sources, we show that the beamline has a high transfer efficiency, and estimate that the percentage of particles captured in the experiments from each bunch is (78 $\pm$ 3)% for up to $10^{5}$ antiprotons, and (71 $\pm$ 5)% for bunches of up to $10^{7}$ positrons.Comment: 15 pages, 15 figure

Alternative Splicing and Nonsense-Mediated RNA Decay Contribute to the Regulation of SHOX Expression

The human SHOX gene is composed of seven exons and encodes a paired-related homeodomain transcription factor. SHOX mutations or deletions have been associated with different short stature syndromes implying a role in growth and bone formation. During development, SHOX is expressed in a highly specific spatiotemporal expression pattern, the underlying regulatory mechanisms of which remain largely unknown. We have analysed SHOX expression in diverse embryonic, fetal and adult human tissues and detected expression in many tissues that were not known to express SHOX before, e.g. distinct brain regions. By using RT-PCR and comparing the results with RNA-Seq data, we have identified four novel exons (exon 2a, 7-1, 7-2 and 7-3) contributing to different SHOX isoforms, and also established an expression profile for the emerging new SHOX isoforms. Interestingly, we found the exon 7 variants to be exclusively expressed in fetal neural tissues, which could argue for a specific role of these variants during brain development. A bioinformatical analysis of the three novel 3′UTR exons yielded insights into the putative role of the different 3′UTRs as targets for miRNA binding. Functional analysis revealed that inclusion of exon 2a leads to nonsense-mediated RNA decay altering SHOX expression in a tissue and time specific manner. In conclusion, SHOX expression is regulated by different mechanisms and alternative splicing coupled with nonsense-mediated RNA decay constitutes a further component that can be used to fine tune the SHOX expression level

Laser cooling of antihydrogen atoms

The photon—the quantum excitation of the electromagnetic field—is massless but carries momentum. A photon can therefore exert a force on an object upon collision1. Slowing the translational motion of atoms and ions by application of such a force2,3, known as laser cooling, was first demonstrated 40 years ago4,5. It revolutionized atomic physics over the following decades6–8, and it is now a workhorse in many fields, including studies on quantum degenerate gases, quantum information, atomic clocks and tests of fundamental physics. However, this technique has not yet been applied to antimatter. Here we demonstrate laser cooling of antihydrogen9, the antimatter atom consisting of an antiproton and a positron. By exciting the 1S–2P transition in antihydrogen with pulsed, narrow-linewidth, Lyman-α laser radiation10,11, we Doppler-cool a sample of magnetically trapped antihydrogen. Although we apply laser cooling in only one dimension, the trap couples the longitudinal and transverse motions of the anti-atoms, leading to cooling in all three dimensions. We observe a reduction in the median transverse energy by more than an order of magnitude—with a substantial fraction of the anti-atoms attaining submicroelectronvolt transverse kinetic energies. We also report the observation of the laser-driven 1S–2S transition in samples of laser-cooled antihydrogen atoms. The observed spectral line is approximately four times narrower than that obtained without laser cooling. The demonstration of laser cooling and its immediate application has far-reaching implications for antimatter studies. A more localized, denser and colder sample of antihydrogen will drastically improve spectroscopic11–13 and gravitational14 studies of antihydrogen in ongoing experiments. Furthermore, the demonstrated ability to manipulate the motion of antimatter atoms by laser light will potentially provide ground-breaking opportunities for future experiments, such as anti-atomic fountains, anti-atom interferometry and the creation of antimatter molecules

Linac-based positron source and generation of a high density positronium cloud for the GBAR experiment

The aim of the recently approved GBAR (Gravitational Behaviour of Antihydrogen at Rest) experiment is to measure the acceleration of neutral antihydrogen atoms in the gravitational field of the Earth. The experimental scheme requires a high density positronium cloud as a target for antiprotons, provided by the Antiproton Decelerator (AD) – Extra Low Energy Antiproton Ring (ELENA) facility at CERN. We introduce briefly the experimental scheme and present the ongoing efforts at IRFU CEA Saclay to develop the positron source and the positron-positronium converter, which are key parts of the experiment. We have constructed a slow positron source in Saclay, based on a low energy (4.3 MeV) linear electron accelerator (linac). By using an electron target made of tungsten and a stack of thin W meshes as positron moderator, we reached a slow positron intensity that is comparable with that of 22Na-based sources using a solid neon moderator. The source feeds positrons into a high field (5 T) Penning-Malmberg trap. Intense positron pulses from the trap will be converted to slow ortho-positronium (o-Ps) by a converter structure. Mesoporous silica films appear to date to be the best candidates as converter material. We discuss our studies to find the optimal pore configuration for the positron-positronium converter