Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons

Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a decreased supply of plasma membrane (PM) in Drosophila class IV dendritic arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis. Transcription factor enrichment analysis identified CREB3L1/CrebA, which regulates COPII gene expression. CrebA overexpression in C4 da neurons restores the dysregulation of COPII genes, GOP synthesis, and PM supply. Chromatin immunoprecipitation (ChIP)-PCR revealed that CrebA expression is regulated by CREB-binding protein (CBP), which is sequestered by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1 synergistically restores the polyQ-induced dendrite pathology. Collectively, our results suggest that GOPs impaired by polyQ proteins contribute to dendrite pathology through the CBP-CrebA-COPII pathway. ? 2017 The Author(s)113Ysciescopu

Measurement of jet suppression in central Pb-Pb collisions at root s(NN)=2.76 TeV

The transverse momentum(p(T)) spectrum and nuclear modification factor (R-AA) of reconstructed jets in 0-10% and 10-30% central Pb-Pb collisions at root s(NN) = 2.76 TeV were measured. Jets were reconstructed using the anti-k(T) jet algorithm with a resolution parameter of R = 0.2 from charged and neutral particles, utilizing the ALICE tracking detectors and Electromagnetic Calorimeter (EMCal). The jet p(T) spectra are reported in the pseudorapidity interval of \eta(jet)\ 5 GeV/c to suppress jets constructed from the combinatorial background in Pb-Pb collisions. The leading charged particle requirement applied to jet spectra both in pp and Pb-Pb collisions had a negligible effect on the R-AA. The nuclear modification factor R-AA was found to be 0.28 +/- 0.04 in 0-10% and 0.35 +/- 0.04 in 10-30% collisions, independent of p(T), jet within the uncertainties of the measurement. The observed suppression is in fair agreement with expectations from two model calculations with different approaches to jet quenching. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.Peer reviewe

Elliptic flow of identified hadrons in Pb-Pb collisions at 1asNN = 2.76 TeV

The elliptic flow coefficient (v2) of identified particles in Pb-Pb collisions at 1asNN = 2.76 TeV was measured with the ALICE detector at the Large Hadron Collider (LHC). The results were obtained with the Scalar Product method, a two-particle corre- lation technique, using a pseudo-rapidity gap of | 06\u3b7| > 0.9 between the identified hadron under study and the reference particles. The v2 is reported for \u3c0\ub1, K\ub1, K0S, p+p, \u3c6, \u39b+\u39b, \u39e 12+\u39e+ and \u3a9 12+\u3a9+ in several collision centralities. In the low transverse momentum (pT) region, pT 3 GeV/c

Centrality dependence of inclusive J/\u3c8 production in p-Pb collisions at 1asNN = 5.02 TeV

We present a measurement of inclusive J/\u3c8 production in p-Pb collisions at 1asNN = 5.02TeV as a function of the centrality of the collision, as estimated from the energy deposited in the Zero Degree Calorimeters. The measurement is performed with the ALICE detector down to zero transverse momentum, pT, in the backward ( 124.46 < ycms < 122.96) and forward (2.03 < ycms < 3.53) rapidity intervals in the dimuon decay channel and in the mid-rapidity region ( 121.37 < ycms < 0.43) in the dielectron decay channel. The backward and forward rapidity intervals correspond to the Pb-going and p-going direction, respectively. The pT-differential J/\u3c8 production cross section at backward and forward rapidity is measured for several centrality classes, together with the corresponding average pT and pT2 values. The nuclear modification factor is presented as a function of centrality for the three rapidity intervals, and as a function of pT for several centrality classes at backward and forward rapidity. At mid- and forward rapidity, the J/\u3c8 yield is suppressed up to 40% compared to that in pp interactions scaled by the number of binary collisions. The degree of suppression increases towards central p-Pb collisions at forward rapidity, and with decreasing pT of the J/\u3c8. At backward rapidity, the nuclear modification factor is compatible with unity within the total uncertainties, with an increasing trend from peripheral to central p-Pb collisions

Centrality dependence of high-pT D meson suppression in Pb-Pb collisions at 1asNN = 2.76 TeV

The nuclear modification factor, RAA, of the prompt charmed mesons D0, D+ and D 17+, and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at a centre-of-mass energy 1asNN = 2.76 TeV in two transverse momentum intervals, 5 < pT < 8GeV/c and 8 < pT < 16GeV/c, and in six collision centrality classes. The RAA shows a maximum suppression of a factor of 5\u20136 in the 10% most central collisions. The suppression and its centrality dependence are compatible within uncertainties with those of charged pions. A comparison with the RAA of non-prompt J/\u3c8 from B meson decays, measured by the CMS Collaboration, hints at a larger suppression of D mesons in the most central collisions

STATUS OF THE LBL/LLL DEVELOPMENT PROGRAM

The status and near-term goals of the LBL/LLL neutral-beam-development program are described. The emphasis in this paper is on the technology of systems based on the acceleration and neutralization of positive ions; this approach will be used in the near term, probably through 1985 at least. For more efficient injection, part of our plan is to develop a negative-ion approach suitable for 200- to 400-kV injectors on confinement experiments in the 1985-90 period. However, the negative-ion based program is still very much in the research phase, and it is difficult to project how it will phase into fusion reactor fueling experiments

Performance of a developmental 120-keV, 10-A deuterium (14-A hydrogen) neutral beam system

We have recently operated the LBL 120-keV neutral beam test facility on deuterium. This facility consists of a large (170,000 l) vacuum system, a plasma source, a multiple-aperture electrostatic accelerator structure, an ion sweep magnet, ion and neutral beam dumps, and a computer diagnostic and control system. The total length of the beamline is about 8.5m. Operation of this test facility on deuterium has produced beams with an energy of 120 keV, a total (ion plus neutral) beam current of 10 A, and a pulse length of 0.5 sec. The beam profile at the location of the dump is bi-gaussian, with 1/e halfwidths of about 1.28 and 0.42 degrees. Deuterium operation has been very limited because of the high neutron production rate (about 10/sup 11/ sec/sup -1/ when the beam is on) and the lack of radiation shielding around the facility