Complexity of the Ruminococcus flavefaciens FD-1 cellulosome reflects an expansion of family-related protein-protein interactions

This work was supported in part by the European Union, Area NMP.2013.1.1–2: Self-assembly of naturally occurring nanosystems: CellulosomePlus Project number: 604530, and by the EU Seventh Framework Programme (FP7 2007–2013) under the WallTraC project (Grant Agreement no 263916), and BioStruct-X (grant agreement no 283570). This paper reflects the author’s views only. The European Community is not liable for any use that may be made of the information contained herein. CMGAF is also supported by Fundação para a Ciência e a Tecnologia (Lisbon, Portugal) through grants PTDC/BIA-PRO/103980/2008 and EXPL/BIA-MIC/1176/2012. EAB is also funded by a grant (No. 1349/13) from the Israel Science Foundation (ISF), Jerusalem, Israel and by a grant (No. 2013284) from the U.S.-Israel Binational Science Foundation (BSF). E.A.B. is the incumbent of The Maynard I. and Elaine Wishner Chair of Bio-organic Chemistry.Peer reviewedPublisher PD

Molecular characterization of the intact mouse muscle spindle using a multi-omics approach

The proprioceptive system is essential for the control of coordinated movement, posture and skeletal integrity. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. Despite its importance, the molecular composition of the muscle spindle is largely unknown. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle isolated from the murine deep masseter muscle. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development. Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease

Development of SRF Cavity Tuners for CERN

Superconducting RF cavity developments are currently on-going for new accelerator projects at CERN such as HIE ISOLDE and HL-LHC. Mechanical RF tuning systems are required to compensate cavity frequency shifts of the cavities due to temperature, mechanical, pressure and RF effects on the cavity geometry. A rich history and experience is available for such mechanical tuners developed for existing RF cavities. Design constraints in the context of HIE ISOLDE and HL-LHC such as required resolution, space limitation, reliability and maintainability have led to new concepts in the tuning mechanisms. This paper will discuss such new approaches, their performances and planned developments

Impaired Nuclear Nrf2 Translocation Undermines the Oxidative Stress Response in Friedreich Ataxia

BACKGROUND: Friedreich ataxia originates from a decrease in mitochondrial frataxin, which causes the death of a subset of neurons. The biochemical hallmarks of the disease include low activity of the iron sulfur cluster-containing proteins (ISP) and impairment of antioxidant defense mechanisms that may play a major role in disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We thus investigated signaling pathways involved in antioxidant defense mechanisms. We showed that cultured fibroblasts from patients with Friedreich ataxia exhibited hypersensitivity to oxidative insults because of an impairment in the Nrf2 signaling pathway, which led to faulty induction of antioxidant enzymes. This impairment originated from previously reported actin remodeling by hydrogen peroxide. CONCLUSIONS/SIGNIFICANCE: Thus, the defective machinery for ISP synthesis by causing mitochondrial iron dysmetabolism increases hydrogen peroxide production that accounts for the increased susceptibility to oxidative stress

AEgIS Experiment: Measuring the Acceleration g of the Earth's Gravitational Field on Antihydrogen Beam

The AEgIS experiment [1] aims at directly measuring the gravitational acceleration g on a beam of cold antihydrogen (H) to a precision of 1%, performing the first test with antimatter of the (WEP) Weak Equivalence Principle. The experimental apparatus is sited at the Antiproton Decelerator (AD) at CERN, Geneva, Switzerland. After production by mixing of antiprotons with Rydberg state positronium atoms (Ps), the atoms will be driven to fly horizontally with a velocity of a few 100 ms−1 for a path length of about 1 meter. The small deflection, few tens of μm, will be measured using two material gratings (of period ∼ 80 μm) coupled to a position-sensitive detector working as a moiré deflectometer similarly to what has been done with matter atoms [2]. The shadow pattern produced by the beam will then be detected by reconstructing the annihilation points with a spatial resolution (∼ 2 μm) of each antiatom at the end of the flight path by the sensitive-position detector. During 2012 the experimental apparatus has been commissioned with antiprotons and positrons. Since the AD will not be running during 2013,during the refurbishment of the CERN accelerators, the experiment is currently working with positrons, electrons and protons, in order to prepare the way for the antihydrogen production in late 2014

Measuring the free fall of antihydrogen

After the first production of cold antihydrogen by the ATHENA and ATRAP experiments ten years ago, new second-generation experiments are aimed at measuring the fundamental properties of this anti-atom. The goal of AEGIS (Antimatter Experiment: Gravity, Interferometry, Spectroscopy) is to test the weak equivalence principle by studying the gravitational interaction between matter and antimatter with a pulsed, cold antihydrogen beam. The experiment is currently being assembled at CERN's Antiproton Decelerator. In AEGIS, antihydrogen will be produced by charge exchange of cold antiprotons with positronium excited to a high Rydberg state (n > 20). An antihydrogen beam will be produced by controlled acceleration in an electric-field gradient (Stark acceleration). The deflection of the horizontal beam due to its free fall in the gravitational field of the earth will be measured with a moire deflectometer. Initially, the gravitational acceleration will be determined to a precision of 1%, requiring the detection of about 105 antihydrogen atoms. In this paper, after a general description, the present status of the experiment will be reviewed

Inter-domain Communication Mechanisms in an ABC Importer: A Molecular Dynamics Study of the MalFGK2E Complex

ATP-Binding Cassette transporters are ubiquitous membrane proteins that convert the energy from ATP-binding and hydrolysis into conformational changes of the transmembrane region to allow the translocation of substrates against their concentration gradient. Despite the large amount of structural and biochemical data available for this family, it is still not clear how the energy obtained from ATP hydrolysis in the ATPase domains is “transmitted” to the transmembrane domains. In this work, we focus our attention on the consequences of hydrolysis and inorganic phosphate exit in the maltose uptake system (MalFGK2E) from Escherichia coli. The prime goal is to identify and map the structural changes occurring during an ATP-hydrolytic cycle. For that, we use extensive molecular dynamics simulations to study three potential intermediate states (with 10 replicates each): an ATP-bound, an ADP plus inorganic phosphate-bound and an ADP-bound state. Our results show that the residues presenting major rearrangements are located in the A-loop, in the helical sub-domain, and in the “EAA motif” (especially in the “coupling helices” region). Additionally, in one of the simulations with ADP we were able to observe the opening of the NBD dimer accompanied by the dissociation of ADP from the ABC signature motif, but not from its corresponding P-loop motif. This work, together with several other MD studies, suggests a common communication mechanism both for importers and exporters, in which ATP-hydrolysis induces conformational changes in the helical sub-domain region, in turn transferred to the transmembrane domains via the “coupling helices”

The Large Hadron-Electron Collider at the HL-LHC

The Large Hadron-Electron Collider (LHeC) is designed to move the field of deep inelastic scattering (DIS) to the energy and intensity frontier of particle physics. Exploiting energy-recovery technology, it collides a novel, intense electron beam with a proton or ion beam from the High-Luminosity Large Hadron Collider (HL-LHC). The accelerator and interaction region are designed for concurrent electron-proton and proton-proton operations. This report represents an update to the LHeC's conceptual design report (CDR), published in 2012. It comprises new results on the parton structure of the proton and heavier nuclei, QCD dynamics, and electroweak and top-quark physics. It is shown how the LHeC will open a new chapter of nuclear particle physics by extending the accessible kinematic range of lepton-nucleus scattering by several orders of magnitude. Due to its enhanced luminosity and large energy and the cleanliness of the final hadronic states, the LHeC has a strong Higgs physics programme and its own discovery potential for new physics. Building on the 2012 CDR, this report contains a detailed updated design for the energy-recovery electron linac (ERL), including a new lattice, magnet and superconducting radio-frequency technology, and further components. Challenges of energy recovery are described, and the lower-energy, high-current, three-turn ERL facility, PERLE at Orsay, is presented, which uses the LHeC characteristics serving as a development facility for the design and operation of the LHeC. An updated detector design is presented corresponding to the acceptance, resolution, and calibration goals that arise from the Higgs and parton-density-function physics programmes. This paper also presents novel results for the Future Circular Collider in electron-hadron (FCC-eh) mode, which utilises the same ERL technology to further extend the reach of DIS to even higher centre-of-mass energies.Peer reviewe