C19orf12 mutation leads to a pallido-pyramidal syndrome.

Pallido-pyramidal syndromes combine dystonia with or without parkinsonism and spasticity as part of a mixed neurodegenerative disorder. Several causative genes have been shown to lead to pallido-pyramidal syndromes, including FBXO7, ATP13A2, PLA2G6, PRKN and SPG11. Among these, ATP13A2 and PLA2G6 are inconsistently associated with brain iron deposition. Using homozygosity mapping and direct sequencing in a multiplex consanguineous Saudi Arabian family with a pallido-pyramidal syndrome, iron deposition and cerebellar atrophy, we identified a homozygous p.G53R mutation in C19orf12. Our findings add to the phenotypic spectrum associated with C19orf12 mutations

BIG enhances Arg/N-degron pathway-mediated protein degradation to regulate Arabidopsis hypoxia responses and suberin deposition

BIG/DARK OVEREXPRESSION OF CAB1/TRANSPORT INHIBITOR RESPONSE3 is a 0.5-MDa protein associated with multiple functions in Arabidopsis (Arabidopsis thaliana) signalling and development. However, the biochemical functions of BIG are unknown. We investigated a role for BIG in the Arg/N-degron pathways, in which substrate protein fate is influenced by the N-terminal (Nt) residue. We crossed a big loss-of-function allele to two N-degron pathway E3 ligase mutants, proteolysis6 (prt6) and prt1, and examined the stability of protein substrates. Stability of model substrates was enhanced in prt6-1 big-2 and prt1-1 big-2 relative to the respective single mutants and the abundance of the PRT6 physiological substrates, HYPOXIA-RESPONSIVE ERF2 (HRE2) and VERNALIZATION2 (VRN2) was similarly increased in prt6 big double mutants. Hypoxia marker expression was enhanced in prt6 big double mutants; this constitutive response required arginyltransferase activity and RAP-type ERFVII transcription factors. Transcriptomic analysis of roots not only demonstrated increased expression of multiple hypoxia-responsive genes in the double mutant relative to prt6, but also revealed other roles for PRT6 and BIG, including regulation of suberin deposition through both ERFVII-dependent and independent mechanisms, respectively. Our results show that BIG acts together with PRT6 to regulate the hypoxia response and broader processes in Arabidopsis

Iron abundances of B-type post-Asymptotic Giant Branch stars in globular clusters: Barnard 29 in M 13 and ROA 5701 in omega Cen

High resolution optical and ultraviolet spectra of two B-type post-Asymptotic Giant Branch (post-AGB) stars in globular clusters, Barnard 29 in M 13 and ROA 5701 in omega Cen, have been analysed using model atmosphere techniques. The optical spectra have been obtained with FEROS on the ESO 2.2-m telescope and the 2d-Coud\'e spectrograph on the 2.7-m McDonald telescope, while the ultraviolet observations are from the GHRS on the HST. Abundances of light elements (C, N, O, Mg, Al and S) plus Fe have been determined from the optical spectra, while the ultraviolet data provide additional Fe abundance estimates from Fe III absorption lines in the 1875-1900 {\AA} wavelength region. A general metal underabundance relative to young B-type stars is found for both Barnard 29 and ROA 5701. These results are consistent with the metallicities of the respective clusters, as well as with previous studies of the objects. The derived abundance patterns suggest that the stars have not undergone a gas-dust separation, contrary to previous suggestions, although they may have evolved from the AGB before the onset of the third dredge-up. However, the Fe abundances derived from the HST spectra are lower than those expected from the metallicities of the respective clusters, by 0.5 dex for Barnard 29 and 0.8 dex for ROA 5701. A similar systematic underabundance is also found for other B-type stars in environments of known metallicity, such as the Magellanic Clouds. These results indicate that the Fe III ultraviolet lines may yield abundance values which are systematically too low by typically 0.6 dex and hence such estimates should be treated with caution.Comment: 15 pages, 3 figures. Accepted for publication in MNRA

Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors

Regenerative efforts typically focus on the delivery of single factors, but it is likely that multiple factors regulating distinct aspects of the regenerative process (e.g., vascularization and stem cell activation) can be used in parallel to affect regeneration of functional tissues. This possibility was addressed in the context of ischemic muscle injury, which typically leads to necrosis and loss of tissue and function. The role of sustained delivery, via injectable gel, of a combination of VEGF to promote angiogenesis and insulin-like growth factor-1 (IGF1) to directly promote muscle regeneration and the return of muscle function in ischemic rodent hindlimbs was investigated. Sustained VEGF delivery alone led to neoangiogenesis in ischemic limbs, with complete return of tissue perfusion to normal levels by 3 weeks, as well as protection from hypoxia and tissue necrosis, leading to an improvement in muscle contractility. Sustained IGF1 delivery alone was found to enhance muscle fiber regeneration and protected cells from apoptosis. However, the combined delivery of VEGF and IGF1 led to parallel angiogenesis, reinnervation, and myogenesis; as satellite cell activation and proliferation was stimulated, cells were protected from apoptosis, the inflammatory response was muted, and highly functional muscle tissue was formed. In contrast, bolus delivery of factors did not have any benefit in terms of neoangiogenesis and perfusion and had minimal effect on muscle regeneration. These results support the utility of simultaneously targeting distinct aspects of the regenerative process.Molecular and Cellular Biolog

Search for High Energy Gamma Rays from an X-ray Selected Blazar Sample

Our understanding of blazars has been greatly increased in recent years by extensive multi-wavelength observations, particularly in the radio, X-ray and gamma-ray regions. Over the past decade the Whipple 10m telescope has contributed to this with the detection of 5 BL Lacertae objects at very high gamma-ray energies. The combination of multi-wavelength data has shown that blazars follow a well-defined sequence in terms of their broadband spectral properties. Together with providing constraints on emission models, this information has yielded a means by which potential sources of TeV emission may be identified and predictions made as to their possible gamma-ray flux. We have used the Whipple telescope to search for TeV gamma-ray emission from eight objects selected from a list of such candidates. No evidence has been found for VHE emission from the objects in our sample, and upper limits have been derived for the mean gamma-ray flux above 390GeV. These flux upper limits are compared with the model predictions and the implications of our results for future observations are discussed.Comment: 15 pages, 2 figures, Accepted for publication in Ap

Understanding interpersonal relationships and psychopathy

Although psychopathy is widely recognised for its importance in forensic and criminal justice settings, the range of interpersonal relationships that are experienced and engaged in by individuals with psychopathy is understudied. A Rapid Evidence Assessment (Study 1) examined what is known empirically about the nature and quality of relationships for individuals with psychopathy. Affective, Cognitive and Lifestyle Assessment (ACL) interviews and genograms were then analysed in conjunction with Psychopathy Checklist: Screening Version (PCL:SV) scores to explore the extent, nature, and quality of interpersonal relationships in student and forensic psychiatric samples (Study 2). Quantitative data indicated that total psychopathy score predicted a smaller number of positive interpersonal relationships. Findings regarding Factors 1 and 2 and numbers of positive and negative interpersonal relationships varied between samples. Qualitative analyses demonstrated that psychopathic participants used less positive descriptors than non-psychopathic participants when discussing their interpersonal relationships. Findings are examined with regards to implications for future research

The TeV spectrum of H1426+428

The BL Lac object H1426+428 was recently detected as a high energy gamma-ray source by the VERITAS collaboration (Horan et al. 2002). We have reanalyzed the 2001 portion of the data used in the detection in order to examine the spectrum of H1426+428 above 250 GeV. We find that the time-averaged spectrum agrees with a power law of the shape dF/dE = 10^(-7.31 +- 0.15(stat) +- 0.16(syst)) x E^(-3.50 +- 0.35(stat) +- 0.05(syst)) m^(-2)s^(-1)TeV^(-1) The statistical evidence from our data for emission above 2.5 TeV is 2.6 sigma. With 95% c.l., the integral flux of H1426+428 above 2.5 TeV is larger than 3% of the corresponding flux from the Crab Nebula. The spectrum is consistent with the (non-contemporaneous) measurement by Aharonian et al. (2002) both in shape and in normalization. Below 800 GeV, the data clearly favours a spectrum steeper than that of any other TeV Blazar observed so far indicating a difference in the processes involved either at the source or in the intervening space.Comment: LaTeX, 8 pages, 4 figures, accepted for publication in Ap

A Search for TeV Gamma-Ray Emission from High-Peaked Flat Spectrum Radio Quasars Using the Whipple Air-Cherenkov Telescope

Blazars have traditionally been separated into two broad categories based upon their optical emission characteristics; BL Lacs, with faint or no emission lines, and flat spectrum radio quasars (FSRQs) with prominent, broad emission lines. The spectral energy distribution of FSRQs has generally been thought of as being more akin to the low-peaked BL Lacs, which exhibit a peak in the infrared region of the spectrum, as opposed to high-peaked BL Lacs (HBLs), which exhibit a peak in UV/X-ray region of the spectrum. All blazars currently confirmed as sources of TeV emission are HBLs. Recent surveys have found several FSRQs exhibiting spectral properties similar to HBLs, particularly the synchrotron peak frequency. These objects are potential sources of TeV emission according to several models of blazar jet emission and blazar evolution. Measurements of TeV flux or upper limits could impact existing theories explaining the links between different blazar types and could have a significant impact on our understanding of the nature of objects that are capable of TeV emission. In particular, the presence (or absence) of TeV emission from FSRQs could confirm (or cast doubt upon) recent evolutionary models that expect intermediate objects in a transitionary state between FSRQ and BL Lac. The Whipple 10 meter imaging air-Cherenkov gamma-ray telescope is well suited for TeV gamma-ray observations. Using the Whipple telescope, we have taken data on a small selection of nearby(z<0.1 in most cases), high-peaked FSRQs. Although one of the objects, B2 0321+33, showed marginal evidence of flaring, no significant emission was detected. The implications of this paucity of emission and the derived upper limits are discussed.Comment: accepted for publication in Astrophysical Journa

New measurement of θ13\theta_{13} via neutron capture on hydrogen at Daya Bay

This article reports an improved independent measurement of neutrino mixing angle $\theta_{13}$ at the Daya Bay Reactor Neutrino Experiment. Electron antineutrinos were identified by inverse $\beta$-decays with the emitted neutron captured by hydrogen, yielding a data-set with principally distinct uncertainties from that with neutrons captured by gadolinium. With the final two of eight antineutrino detectors installed, this study used 621 days of data including the previously reported 217-day data set with six detectors. The dominant statistical uncertainty was reduced by 49%. Intensive studies of the cosmogenic muon-induced $^9$Li and fast neutron backgrounds and the neutron-capture energy selection efficiency, resulted in a reduction of the systematic uncertainty by 26%. The deficit in the detected number of antineutrinos at the far detectors relative to the expected number based on the near detectors yielded $\sin^22\theta_{13} = 0.071 \pm 0.011$ in the three-neutrino-oscillation framework. The combination of this result with the gadolinium-capture result is also reported.Comment: 26 pages, 23 figure