Observation of a J^PC = 1-+ exotic resonance in diffractive dissociation of 190 GeV/c pi- into pi- pi- pi+

The COMPASS experiment at the CERN SPS has studied the diffractive dissociation of negative pions into the pi- pi- pi+ final state using a 190 GeV/c pion beam hitting a lead target. A partial wave analysis has been performed on a sample of 420000 events taken at values of the squared 4-momentum transfer t' between 0.1 and 1 GeV^2/c^2. The well-known resonances a1(1260), a2(1320), and pi2(1670) are clearly observed. In addition, the data show a significant natural parity exchange production of a resonance with spin-exotic quantum numbers J^PC = 1-+ at 1.66 GeV/c^2 decaying to rho pi. The resonant nature of this wave is evident from the mass-dependent phase differences to the J^PC = 2-+ and 1++ waves. From a mass-dependent fit a resonance mass of 1660 +- 10+0-64 MeV/c^2 and a width of 269+-21+42-64 MeV/c^2 is deduced.Comment: 7 page, 3 figures; version 2 gives some more details, data unchanged; version 3 updated authors, text shortened, data unchange

FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation

FUsed in Sarcoma (FUS) is a multifunctional RNA binding protein (RBP). FUS mutations lead to its cytoplasmic mislocalization and cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Here, we use mouse and human models with endogenous ALS-associated mutations to study the early consequences of increased cytoplasmic FUS. We show that in axons, mutant FUS condensates sequester and promote the phase separation of fragile X mental retardation protein (FMRP), another RBP associated with neurodegeneration. This leads to repression of translation in mouse and human FUS-ALS motor neurons and is corroborated in vitro, where FUS and FMRP copartition and repress translation. Last, we show that translation of FMRP-bound RNAs is reduced in vivo in FUS-ALS motor neurons. Our results unravel new pathomechanisms of FUS-ALS and identify a novel paradigm by which mutations in one RBP favor the formation of condensates sequestering other RBPs, affecting crucial biological functions, such as protein translation

C9orf72 arginine-rich dipeptide proteins interact with ribosomal proteins in vivo to induce a toxic translational arrest that is rescued by eIF1A.

A GGGGCC hexanucleotide repeat expansion within the C9orf72 gene is the most common genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia. Sense and antisense repeat-containing transcripts undergo repeat-associated non-AUG-initiated translation to produce five dipeptide proteins (DPRs). The polyGR and polyPR DPRs are extremely toxic when expressed in Drosophila neurons. To determine the mechanism that mediates this toxicity, we purified DPRs from the Drosophila brain and used mass spectrometry to identify the in vivo neuronal DPR interactome. PolyGR and polyPR interact with ribosomal proteins, and inhibit translation in both human iPSC-derived motor neurons, and adult Drosophila neurons. We next performed a screen of 81 translation-associated proteins in GGGGCC repeat-expressing Drosophila to determine whether this translational repression can be overcome and if this impacts neurodegeneration. Expression of the translation initiation factor eIF1A uniquely rescued DPR-induced toxicity in vivo, indicating that restoring translation is a potential therapeutic strategy. These data directly implicate translational repression in C9orf72 repeat-induced neurodegeneration and identify eIF1A as a novel modifier of C9orf72 repeat toxicity

On-line mirror alignment monitoring method for COMPASS RICH-1 RID D-9840-2011

COMPASS RICH-1 is a large size gaseous Cherenkov detector. Two reflecting spherical surfaces, covering a total area of about View the MathML source21m2 hosted in the radiator vessel provide image focusing. The segmented surfaces are formed by 116 mirrors, with individual degrees of freedom for angular adjustment. An original method has been developed and applied for the on-line monitoring of the mirror alignment. Relative tilts between neighbouring mirror elements create discontinuities in the image of continuous lines reflected by the mirror wall. The measurement of the discontinuities can also provide information about the absolute tilt with a resolution of 0.1 mrad. An independent check and calibration of this method has been performed in laboratory using, as reference, a laser interferometer. We present the technical solutions adopted to implement the dedicated setup, the results of the method calibration by laser interferometer, and the preliminary results obtained measuring the alignment of the RICH-1 mirror wall

Deubiquitinase-based analysis of ubiquitin chain architecture using Ubiquitin Chain Restriction (UbiCRest)

Protein ubiquitination is a versatile protein modification that regulates virtually all cellular processes. This versatility originates from polyubiquitin chains, which can be linked in eight distinct ways. The combinatorial complexity of eight linkage types in homotypic (one chain type per polymer) and heterotypic (multiple linkage types per polymer) chains poses significant problems for biochemical analysis. Here we describe UbiCRest, in which substrates (ubiquitinated proteins or polyubiquitin chains) are treated with a panel of linkage-specific deubiquitinating enzymes (DUBs) in parallel reactions, followed by gel-based analysis. UbiCRest can be used to show that a protein is ubiquitinated, to identify which linkage type(s) are present on polyubiquitinated proteins and to assess the architecture of heterotypic polyubiquitin chains. DUBs used in UbiCRest can be obtained commercially; however, we include details for generating a toolkit of purified DUBs and for profiling their linkage preferences in vitro. UbiCRest is a qualitative method that yields insights into ubiquitin chain linkage types and architecture within hours, and it can be performed on western blotting quantities of endogenously ubiquitinated proteins

THGEM based photon detector for Cherenkov imaging applications

We are developing a single photon detector for Cherenkov imaging counters. This detector is based on the use of THGEM electron multipliers in a multilayer design. The major goals of our project are ion feedback suppression down to a few per cent, large gain, fast response, insensitivity to magnetic fields, and a large detector size. We report about the project status and perspectives. In particular, we present a systematic study of the THGEM response as a function of geometrical parameters, production techniques and the gas mixture composition. The first figures obtained from measuring the response of a CsI coated THGEM to single photons are presented

Micropattern gaseous photon detectors for Cherenkov imaging counters RID D-9840-2011

We are developing a detector of single photons for application in Cherenkov imaging counters, based on the use of a multilayer architecture of THGEM electron multipliers coupled to a solid state CsI photocathode. The main goals of our project are ion feedback suppression down to a few per cent level, large gain, fast response, good time resolution, insensitivity to magnetic field and large detector size. We report about the project status and perspectives

The quest for a third generation of gaseous photon detectors for Cherenkov imaging counters

RICH (Ring Imaging CHerenkov) counters for PID in the high momentum domain and in large acceptance experiments require photon detectors covering extended surface (several square meters) and able to accept Cherenkov photons in a wide angular range. An ideal approach is represented by gaseous photon detectors, which allow covering wide surfaces at affordable costs. The first generation of these detectors was based on the use of organic vapors. The second generation consists of CsI photocathodes and open geometry gaseous detectors (MWPC). In spite of the success of this approach, some limits of the technique arise from the bombardment of the photocathodes by the ions generated in the amplification process and by the photon feedback. A third generation of gaseous photon detectors using closed geometry, as those possible with multistage arrangements of micropattern gaseous detectors, can overcome the observed limitations. We have started an R&D programme to develop a Thick-GEM-based photon detector and we report about our initial studie