Locomotor hyperactivity in 14-3-3Zeta KO mice is associated with dopamine transporter dysfunction

Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions that are tightly linked to catecholamine exocytosis and receptor interactions on pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily achieved through reuptake of extracellular DA by the DA transporter (DAT) on presynaptic neurons. Aberrant regulation of DA signalling, and in particular hyperactivation, has been proposed as a key insult in the presentation of schizophrenia and related neuropsychiatric disorders. We recently identified 14-3-3ζ as an essential component of neurodevelopment and a central risk factor in the schizophrenia protein interaction network. Our analysis of 14-3-3ζ-deficient mice now shows that baseline hyperactivity of knockout (KO) mice is rescued by the antipsychotic drug clozapine. 14-3-3ζ KO mice displayed enhanced locomotor hyperactivity induced by the DA releaser amphetamine. Consistent with 14-3-3ζ having a role in DA signalling, we found increased levels of DA in the striatum of 14-3-3ζ KO mice. Although 14-3-3ζ is proposed to modulate activity of the rate-limiting DA biosynthesis enzyme, tyrosine hydroxylase (TH), we were unable to identify any differences in total TH levels, TH localization or TH activation in 14-3-3ζ KO mice. Rather, our analysis identified significantly reduced levels of DAT in the absence of notable differences in RNA or protein levels of DA receptors D1–D5. Providing insight into the mechanisms by which 14-3-3ζ controls DAT stability, we found a physical association between 14-3-3ζ and DAT by co-immunoprecipitation. Taken together, our results identify a novel role for 14-3-3ζ in DA neurotransmission and provide support to the hyperdopaminergic basis of pathologies associated with schizophrenia and related disorders.H Ramshaw, X Xu, EJ Jaehne, P McCarthy, Z Greenberg, E Saleh, B McClure, J Woodcock, S Kabbara, S Wiszniak, Ting-Yi Wang, C Parish, M van den Buuse, BT Baune, A Lopez and Q Schwar

Stringy effects in black hole decay

We compute the low energy decay rates of near-extremal three(four) charge black holes in five(four) dimensional N=4 string theory to sub-leading order in the large charge approximation. This involves studying stringy corrections to scattering amplitudes of a scalar field off a black hole. We adapt and use recently developed techniques to compute such amplitudes as near-horizon quantities. We then compare this with the corresponding calculation in the microscopic configuration carrying the same charges as the black hole. We find perfect agreement between the microscopic and macroscopic calculations; in the cases we study, the zero energy limit of the scattering cross section is equal to four times the Wald entropy of the black hole.Comment: 32 page

Hip strength: Ankle proprioceptive threshold ratio predicts falls and injury in diabetic neuropathy

Introduction : We determined lower limb neuromuscular capacities associated with falls and fall‐related injuries in older people with declining peripheral nerve function. Methods : Thirty‐two subjects (67.4 ± 13.4 years; 19 with type 2 diabetes), representing a spectrum of peripheral neurologic function, were evaluated with frontal plane proprioceptive thresholds at the ankle, frontal plane motor function at the ankle and hip, and prospective follow‐up for 1 year. Results : Falls and fall‐related injuries were reported by 20 (62.5%) and 14 (43.8%) subjects, respectively. The ratio of hip adductor rate of torque development to ankle proprioceptive threshold (Hip STR /Ank PRO ) predicted falls (pseudo‐R 2  = .726) and injury (pseudo‐R 2  = .382). No other variable maintained significance in the presence of Hip STR /Ank PRO . Conclusions : Fall and injury risk in the population studied is related inversely to Hip STR /Ank PRO . Increasing rapidly available hip strength in patients with neuropathic ankle sensory impairment may decrease risk of falls and related injuries. Muscle Nerve 50 : 437–442, 2014Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108329/1/mus24134.pd

Quality of life among people living with hypertension in a rural Vietnam community

Background - To respond to growing prevalence of hypertension in Vietnam, it is critical to have an in-depth understanding about quality of life (QOL) among people living with hypertension and related factors. This study aimed to measure QOL among hypertensive people in a rural community in Vietnam, and its association with socio-demographic characteristics and factors related to treatment. Methods - This study was conducted in a rural community located 60 km from Ho Chi Minh City. Face-to-face interviews were conducted among 275 hypertensive people aged 50 years and above using WHOQOL-BREF questionnaire. Descriptive statistics were used to examine mean scores of quality of life. Cronbach’s alpha coefficient and Pearson’s correlation coefficient were applied to estimate the internal consistency, and the level of agreement between different domains of WHOQOL-BREF, respectively. Independent T-test and ANOVA test followed by multiple linear regression analyses were used to measure the association between QOL domains and independent variables. Results - Both overall WHOQOL-BREF and each domain had a good internal consistency, ranging from 0.65 to 0.88. The QOL among hypertensive patients was found moderate in all domains, except for psychological domain that was fairly low (mean = 49.4). Backward multiple linear regressions revealed that being men, married, attainment of higher education, having physical activities at moderate level, and adherence to treatment were positively associated with QOL. However, older age and presence of co-morbidity were negatively associated with QOL. Conclusion - WHOQOL-BREF is a reliable instrument to measure QOL among hypertensive patients. The results revealed low QOL in psychological domain and inequality in QOL across socio-demographic characteristics. Given the results, encouraging physical activities and strengthening treatment adherence should be considered to improve QOL of hypertensive people, especially for psychological aspect. Actions to improve QOL among hypertensive patients targeted towards women, lower educated and unmarried patients are needed in the setting

Holographic Vitrification

We establish the existence of stable and metastable stationary black hole bound states at finite temperature and chemical potentials in global and planar four-dimensional asymptotically anti-de Sitter space. We determine a number of features of their holographic duals and argue they represent structural glasses. We map out their thermodynamic landscape in the probe approximation, and show their relaxation dynamics exhibits logarithmic aging, with aging rates determined by the distribution of barriers.Comment: 100 pages, 25 figure

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO