The ISWI Chromatin Remodeler Organizes the hsrω ncRNA–Containing Omega Speckle Nuclear Compartments

The complexity in composition and function of the eukaryotic nucleus is achieved through its organization in specialized nuclear compartments. The Drosophila chromatin remodeling ATPase ISWI plays evolutionarily conserved roles in chromatin organization. Interestingly, ISWI genetically interacts with the hsrω gene, encoding multiple non-coding RNAs (ncRNA) essential, among other functions, for the assembly and organization of the omega speckles. The nucleoplasmic omega speckles play important functions in RNA metabolism, in normal and stressed cells, by regulating availability of hnRNPs and some other RNA processing proteins. Chromatin remodelers, as well as nuclear speckles and their associated ncRNAs, are emerging as important components of gene regulatory networks, although their functional connections have remained poorly defined. Here we provide multiple lines of evidence showing that the hsrω ncRNA interacts in vivo and in vitro with ISWI, regulating its ATPase activity. Remarkably, we found that the organization of nucleoplasmic omega speckles depends on ISWI function. Our findings highlight a novel role for chromatin remodelers in organization of nucleoplasmic compartments, providing the first example of interaction between an ATP-dependent chromatin remodeler and a large ncRNA

Transcutaneous vagus nerve stimulation combined with robotic rehabilitation improves upper limb function after stroke

The efficacy of standard rehabilitative therapy for improving upper limb functions after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) paired with rehabilitation is a promising approach, but the invasiveness of this technique limits its clinical application. Recently, a noninvasive method to stimulate vagus nerve has been developed. The aim of the present study was to explore whether noninvasive VNS combined with robotic rehabilitation can enhance upper limb functionality in chronic stroke. Safety and efficacy of this combination have been assessed within a proof-of-principle, double-blind, semirandomized, sham-controlled trial. Fourteen patients with either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted therapy associated with real or sham VNS, delivered for 10 working days. Efficacy was evaluated by change in upper extremity Fugl-Meyer score. After intervention, there were no adverse events and Fugl-Meyer scores were significantly better in the real group compared to the sham group. Our pilot study confirms that VNS is feasible in stroke patients and can produce a slight clinical improvement in association to robotic rehabilitation. Compared to traditional stimulation, noninvasive VNS seems to be safer and more tolerable. Further studies are needed to confirm the efficacy of this innovative approach

Solstice: An Electronic Journal of Geography and Mathematics, Volume XIV, Number 2

This document was delivered over the internet. The .zip file contains all static images, animated images, and text files.The purpose of Solstice is to promote interaction between geography and mathematics. Articles in which elements of one discipline are used to shed light on the other are particularly sought. Also welcome, are original contributions that are purely geographical or purely mathematical. These may be prefaced (by editor or author) with commentary suggesting directions that might lead toward the desired interaction. Contributed articles will be refereed by geographers and/or mathematicians. Invited articles will be screened by suitable members of the editorial board. IMaGe is open to having authors suggest, and furnish material for, new regular features.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58247/2/win03.ziphttp://deepblue.lib.umich.edu/bitstream/2027.42/58247/3/2003SolsticeVol14.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/58247/5/SolsticeVolXIVNo2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/58247/6/SolsticeVolXIVNo2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/58247/8/SolsticeVolXIVNo2.pdfDescription of SolsticeVolXIVNo2.pdf : Cover of JournalDescription of 2003SolsticeVol14.pdf : Solstice, 2003, Numbers 1 and 2. Contains attachments.Description of SolsticeVolXIVNo2.pdf : Cover of JournalDescription of SolsticeVolXIVNo2.pdf : Cover fil

Solstice: An Electronic Journal of Geography and Mathematics, Volume XVI, Number 1

This document was delivered over the internet. The .zip file contains all static images, animated images, and text files.The purpose of Solstice is to promote interaction between geography and mathematics. Articles in which elements of one discipline are used to shed light on the other are particularly sought. Also welcome, are original contributions that are purely geographical or purely mathematical. These may be prefaced (by editor or author) with commentary suggesting directions that might lead toward the desired interaction. Contributed articles will be refereed by geographers and/or mathematicians. Invited articles will be screened by suitable members of the editorial board. IMaGe is open to having authors suggest, and furnish material for, new regular features.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58253/2/sum05.ziphttps://deepblue.lib.umich.edu/bitstream/2027.42/58253/3/SolsticeVolXVINo1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/58253/5/SolsticeVolXVINo1.pdfDescription of SolsticeVolXVINo1.pdf : Cover of JournalDescription of SolsticeVolXVINo1.pdf : Cover fil

Delayed pain decrease following M1 tDCS in spinal cord injury: A randomized controlled clinical trial

Despite some encouraging findings for the treatment of neuropathic pain in patients with spinal cord injury (SCI), transcranial direct current stimulation (tDCS) directed to the primary motor cortex (M1) has faced some mixed results. Prior to translating this technology to clinical care, consistent results and durable effects need to be found. We, therefore, aimed to assess the direct and long-term effects of tDCS on pain following SCI.We performed a two-phase randomized sham-controlled clinical trial where patients received 5 days of tDCS followed by a 3-month follow-up period (Phase I); then, Phase II consisted of 10 days of tDCS with an 8-week follow-up period. We assessed the level of pain with the Visual Analogue Scale (VAS). Patients' quality of life and life satisfaction were also evaluated.33 patients were enrolled in Phase I and 9 in Phase II. We observed a treatment effect at 1-week follow-up for Phase I and at 4-week follow-up for Phase II. The overall level of pain was significantly lower for the active group, as compared to sham, in Phase II.Our exploratory study shows that tDCS does seem to be a promising tool to manage pain in patients with SCI and repeated stimulation sessions are needed to induce long-lasting effects. Based on our protocol, it appears that adding a second treatment period could induce long-lasting effects.This project was supported by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant numbers 90DP0035 and H133N110010)

The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation.

A single microRNA (miRNA) can regulate the expression of many genes, though the level of repression imparted on any given target is generally low. How then is the selective pressure for a single miRNA/target interaction maintained across long evolutionary distances? We addressed this problem by disrupting in vivo the interaction between miR-155 and PU.1 in mice. Remarkably, this interaction proved to be key to promoting optimal T cell-dependent B cell responses, a previously unrecognized role for PU.1. Mechanistically, miR-155 inhibits PU.1 expression, leading to Pax5 down-regulation and the initiation of the plasma cell differentiation pathway. Additional PU.1 targets include a network of genes whose products are involved in adhesion, with direct links to B-T cell interactions. We conclude that the evolutionary adaptive selection of the miR-155-PU.1 interaction is exercised through the effectiveness of terminal B cell differentiation

Evolutionary Dynamics of Human Toll-Like Receptors and Their Different Contributions to Host Defense

Infectious diseases have been paramount among the threats to health and survival throughout human evolutionary history. Natural selection is therefore expected to act strongly on host defense genes, particularly on innate immunity genes whose products mediate the direct interaction between the host and the microbial environment. In insects and mammals, the Toll-like receptors (TLRs) appear to play a major role in initiating innate immune responses against microbes. In humans, however, it has been speculated that the set of TLRs could be redundant for protective immunity. We investigated how natural selection has acted upon human TLRs, as an approach to assess their level of biological redundancy. We sequenced the ten human TLRs in a panel of 158 individuals from various populations worldwide and found that the intracellular TLRs—activated by nucleic acids and particularly specialized in viral recognition—have evolved under strong purifying selection, indicating their essential non-redundant role in host survival. Conversely, the selective constraints on the TLRs expressed on the cell surface—activated by compounds other than nucleic acids—have been much more relaxed, with higher rates of damaging nonsynonymous and stop mutations tolerated, suggesting their higher redundancy. Finally, we tested whether TLRs have experienced spatially-varying selection in human populations and found that the region encompassing TLR10-TLR1-TLR6 has been the target of recent positive selection among non-Africans. Our findings indicate that the different TLRs differ in their immunological redundancy, reflecting their distinct contributions to host defense. The insights gained in this study foster new hypotheses to be tested in clinical and epidemiological genetics of infectious disease

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Pseudorapidity and transverse-momentum distributions of charged particles in proton-proton collisions at root s=13 TeV

The pseudorapidity (eta) and transverse-momentum (p(T)) distributions of charged particles produced in proton-proton collisions are measured at the centre-of-mass energy root s = 13 TeV. The pseudorapidity distribution in vertical bar eta vertical bar <1.8 is reported for inelastic events and for events with at least one charged particle in vertical bar eta vertical bar <1. The pseudorapidity density of charged particles produced in the pseudorapidity region vertical bar eta vertical bar <0.5 is 5.31 +/- 0.18 and 6.46 +/- 0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15 <p(T) <20 GeV/c and vertical bar eta vertical bar <0.8 for events with at least one charged particle in vertical bar eta vertical bar <1. The evolution of the transverse momentum spectra of charged particles is also investigated as a function of event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Elliptic flow of muons from heavy-flavour hadron decays at forward rapidity in Pb-Pb collisions at root s(NN)=2.76TeV

The elliptic flow, v(2), of muons from heavy-flavour hadron decays at forward rapidity (2.5 <y <4) is measured in Pb-Pb collisions at root s(NN)= 2.76TeVwith the ALICE detector at the LHC. The scalar product, two- and four-particle Q cumulants and Lee-Yang zeros methods are used. The dependence of the v(2) of muons from heavy-flavour hadron decays on the collision centrality, in the range 0-40%, and on transverse momentum, p(T), is studied in the interval 3 <p(T)<10 GeV/c. A positive v(2) is observed with the scalar product and two-particle Q cumulants in semi-central collisions (10-20% and 20-40% centrality classes) for the p(T) interval from 3 to about 5GeV/c with a significance larger than 3 sigma, based on the combination of statistical and systematic uncertainties. The v(2) magnitude tends to decrease towards more central collisions and with increasing pT. It becomes compatible with zero in the interval 6 <p(T)<10 GeV/c. The results are compared to models describing the interaction of heavy quarks and open heavy-flavour hadrons with the high-density medium formed in high-energy heavy-ion collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.Peer reviewe