A systematic review of genome-wide association studies for pain, nociception, neuropathy, and pain treatment responses

Pain is the leading cause of disability worldwide, imposing an enormous burden on personal health and society. Pain is a multifactorial and multidimensional problem. Currently, there is (some) evidence that genetic factors could partially explain individual susceptibility to pain and interpersonal differences in pain treatment response. To better understand the underlying genetic mechanisms of pain, we systematically reviewed and summarized genome-wide association studies (GWASes) investigating the associations between genetic variants and pain/pain-related phenotypes in humans. We reviewed 57 full-text articles and identified 30 loci reported in more than 1 study. To check whether genes described in this review are associated with (other) pain phenotypes, we searched 2 pain genetic databases, Human Pain Genetics Database and Mouse Pain Genetics Database. Six GWAS-identified genes/loci were also reported in those databases, mainly involved in neurological functions and inflammation. These findings demonstrate an important contribution of genetic factors to the risk of pain and pain-related phenotypes. However, replication studies with consistent phenotype definitions and sufficient statistical power are required to validate these pain-associated genes further. Our review also highlights the need for bioinformatic tools to elucidate the function of identified genes/loci. We believe that a better understanding of the genetic background of pain will shed light on the underlying biological mechanisms of pain and benefit patients by improving the clinical management of pain.</p

Parton distribution functions and quark orbital motion

Covariant version of the quark-parton model is studied. Dependence of the structure functions and parton distributions on the 3D quark intrinsic motion is discussed. The important role of the quark orbital momentum, which is a particular case of intrinsic motion, appears as a direct consequence of the covariant description. Effect of orbital motion is substantial especially for polarized structure functions. At the same time, the procedure for obtaining the quark momentum distributions of polarized quarks from the combination of polarized and unpolarized structure functions is suggested.Comment: 17 pages, 2 figures, 1 table. Paper is accepted for publication in Eur.Phys.J.

EGAM Induced by Energetic-electrons and Nonlinear Interactions among EGAM, BAEs and Tearing Modes in a Toroidal Plasma

In this letter, it is reported that the first experimental results are associated with the GAM induced by energetic electrons (eEGAM) in HL-2A Ohmic plasma. The energetic-electrons are generated by parallel electric fields during magnetic reconnection associated with tearing mode (TM). The eEGAM localizes in the core plasma, i.e. in the vicinity of q=2 surface, and is very different from one excited by the drift-wave turbulence in the edge plasma. The analysis indicated that the eEGAM is provided with the magnetic components, whose intensities depend on the poloidal angles, and its mode numbers are jm/nj=2/0. Further, there exist intense nonlinear interactions among eEGAM, BAEs and strong tearing modes (TMs). These new findings shed light on the underlying physics mechanism for the excitation of the low frequency (LF) Alfv\'enic and acoustic uctuations.Comment: 5 pages,4 figure

The rms-flux relations in different branches in Cyg X-2

In this paper, the rms-flux (root mean square-flux) relation along the Z-track of the bright Z-Source Cyg X-2 is analyzed using the observational data of Rossi X-ray Timing Explorer (RXTE). Three types of rms-flux relations, i.e. positive, negative, and 'arch'-like correlations are found in different branches. The rms is positively correlated with flux in normal branch (NB), but anti-correlated in the vertical horizontal branch (VHB). The rms-flux relation shows an 'arch'-like shape in the horizontal branch (HB). We also try to explain this phenomenon using existing models.Comment: Accepted for publication in Astrophysics & Space Scienc

Measurement of the Proton and Deuteron Spin Structure Functions g2 and Asymmetry A2

We have measured the spin structure functions g2p and g2d and the virtual photon asymmetries A2p and A2d over the kinematic range 0.02 < x < 0.8 and 1.0 < Q^2 < 30(GeV/c)^2 by scattering 38.8 GeV longitudinally polarized electrons from transversely polarized NH3 and 6LiD targets.The absolute value of A2 is significantly smaller than the sqrt{R} positivity limit over the measured range, while g2 is consistent with the twist-2 Wandzura-Wilczek calculation. We obtain results for the twist-3 reduced matrix elements d2p, d2d and d2n. The Burkhardt-Cottingham sum rule integral - int(g2(x)dx) is reported for the range 0.02 < x < 0.8.Comment: 12 pages, 4 figures, 1 tabl

Shapes, contact angles, and line tensions of droplets on cylinders

Using an interface displacement model we calculate the shapes of nanometer-size liquid droplets on homogeneous cylindrical surfaces. We determine effective contact angles and line tensions, the latter defined as excess free energies per unit length associated with the two contact lines at the ends of the droplet. The dependences of these quantities on the cylinder radius and on the volume of the droplets are analyzed.Comment: 26 pages, RevTeX, 10 Figure

CP Phases in Correlated Production and Decay of Neutralinos in the Minimal Supersymmetric Standard Model

We investigate the associated production of neutralinos $e^+e^-\to\tilde{\chi}^0_1\tilde{\chi}^0_2$ accompanied by the neutralino leptonic decay $\tilde{\chi}^0_2\to\tilde{\chi}^0_1 \ell^+\ell^-$, taking into account initial beam polarization and production-decay spin correlations in the minimal supersymmetric standard model with general CP phases but without generational mixing in the slepton sector. The stringent constraints from the electron EDM on the CP phases are also included in the discussion. Initial beam polarizations lead to three CP--even distributions and one CP--odd distribution, which can be studied independently of the details of the neutralino decays. We find that the production cross section and the branching fractions of the leptonic neutralino decays are very sensitive to the CP phases. In addition, the production--decay spin correlations lead to several CP--even observables such as lepton invariant mass distribution, and lepton angular distribution, and one interesting T--odd (CP--odd) triple product of the initial electron momentum and two final lepton momenta, the size of which might be large enough to be measured at the high--luminosity future electron--positron collider or can play a complementary role in constraining the CP phases with the EDM constraints.Comment: Revtex, 37 pages, 12 eps figure

Visual processing deficits in 22q11.2 Deletion Syndrome.

Carriers of the rare 22q11.2 microdeletion present with a high percentage of positive and negative symptoms and a high genetic risk for schizophrenia. Visual processing impairments have been characterized in schizophrenia, but less so in 22q11.2 Deletion Syndrome (DS). Here, we focus on visual processing using high-density EEG and source imaging in 22q11.2DS participants (N = 25) and healthy controls (N = 26) with an illusory contour discrimination task. Significant differences between groups emerged at early and late stages of visual processing. In 22q11.2DS, we first observed reduced amplitudes over occipital channels and reduced source activations within dorsal and ventral visual stream areas during the P1 (100-125 ms) and within ventral visual cortex during the N1 (150-170 ms) visual evoked components. During a later window implicated in visual completion (240-285 ms), we observed an increase in global amplitudes in 22q11.2DS. The increased surface amplitudes for illusory contours at this window were inversely correlated with positive subscales of prodromal symptoms in 22q11.2DS. The reduced activity of ventral and dorsal visual areas during early stages points to an impairment in visual processing seen both in schizophrenia and 22q11.2DS. During intervals related to perceptual closure, the inverse correlation of high amplitudes with positive symptoms suggests that participants with 22q11.2DS who show an increased brain response to illusory contours during the relevant window for contour processing have less psychotic symptoms and might thus be at a reduced prodromal risk for schizophrenia

SUMO-2 and PIAS1 modulate insoluble mutant Huntingtin protein accumulation

A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin (HTT) protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression