Spinocerebellar ataxia type 8 larger triplet expansion alters histone modification and induces RNA foci

<p>Abstract</p> <p>Background</p> <p>Spinocerebellar ataxia type 8 (SCA8) involves the expression of an expanded CTG/CAG combined repeats (CR) from opposite strands producing CUG expansion transcripts (ataxin 8 opposite strand, ATXN8OS) and a polyglutamine expansion protein (ataxin 8, ATXN8). The pathogenesis of SCA8 is complex and the spectrum of clinical presentations is broad.</p> <p>Results</p> <p>Using stably induced cell models expressing 0, 23, 88 and 157 CR, we study the role of ATXN8OS transcripts in SCA8 pathogenesis. In the absence of doxycycline, the stable ATXN8OS CR cell lines exhibit low levels of ATXN8OS expression and a repeat length-related increase in staurosporine sensitivity and in the number of annexin positive cells. A repeat length-dependent repression of ATXN8OS expression was also notable. Addition of doxycycline leads to 25~50 times more ATXN8OS RNA expression with a repeat length-dependent increase in fold of ATXN8OS RNA induction. ChIP-PCR assay using anti-dimethyl-histone H3-K9 and anti-acetyl-histone H3-K14 antibodies revealed increased H3-K9 dimethylation and reduced H3-K14 acetylation around the ATXN8OS cDNA gene in 157 CR line. The repeat length-dependent increase in induction fold is probably due to the increased RNA stability as demonstrated by monitoring ATXN8OS RNA decay in cells treated with the transcriptional inhibitor, actinomycin D. In cells stably expressing ATXN8OS, RNA FISH experiments further revealed ribonuclear foci formation in cells carrying expanded 88 and 157 CR.</p> <p>Conclusion</p> <p>The present study demonstrates that the expanded CUG-repeat tracts are toxic to human cells and may affect ATXN8OS RNA expression and stability through epigenetic and post-transcriptional mechanisms.</p

Phase diagram and symmetry breaking of SU(4) spin-orbital chain in a generalized external field

The ground state phases of a one-dimensional SU(4) spin-orbital Hamiltonian in a generalized external field are studied on the basis of Bethe-ansatz solution. Introducing three Land\'e $g$ factors for spin, orbital and their products in the SU(4) Zeeman term, we discuss systematically the various symmetry breaking. The magnetization versus external field are obtained by solving Bethe-ansatz equations numerically. The phase diagrams corresponding to distinct residual symmetries are given by means of both numerical and analytical methods.Comment: Revtex4, 16 pages, 7 figure

Merging Galaxies in the SDSS EDR

We present a new catalog of merging galaxies obtained through an automated systematic search routine. The 1479 new pairs of merging galaxies were found in approximately 462 sq deg of the Sloan Digital Sky Survey Early Data Release (SDSS EDR; Stoughton et al. 2002) photometric data, and the pair catalog is complete for galaxies in the magnitude range 16.0 <= g* <= 20. The selection algorithm, implementing a variation on the original Karachentsev (1972) criteria, proved to be very efficient and fast. Merging galaxies were selected such that the inter-galaxy separations were less than the sum of the component galaxies' radii. We discuss the characteristics of the sample in terms of completeness, pair separation, and the Holmberg effect. We also present an online atlas of images for the SDSS EDR pairs obtained using the corrected frames from the SDSS EDR database. The atlas images also include the relevant data for each pair member. This catalog will be useful for conducting studies of the general characteristics of merging galaxies, their environments, and their component galaxies. The redshifts for a subset of the interacting and merging galaxies and the distribution of angular sizes for these systems indicate the SDSS provides a much deeper sample than almost any other wide-area catalog to date.Comment: 58 pages, which includes 15 figures and 6 tables. Figures 2, 8, 9, 10, 11, 13, and 14 are provided as JPEG files. For online atlas, see http://home.fnal.gov/~sallam/MergePair/ . Accepted for publication in A

Effectiveness of Pandemic H1N1-2009 Vaccination in Reducing Laboratory Confirmed Influenza Infections among Military Recruits in Tropical Singapore

10.1371/journal.pone.0026572PLoS ONE610

Seroconversion and asymptomatic infections during oseltamivir prophylaxis against Influenza A H1N1 2009

<p>Abstract</p> <p>Background</p> <p>Anti-viral prophylaxis is used to prevent the transmission of influenza. We studied serological confirmation of 2009 Influenza A (H1N1) infections during oseltamivir prophylaxis and after cessation of prophylaxis.</p> <p>Methods</p> <p>Between 22 Jun and 16 Jul 09, we performed a cohort study in 3 outbreaks in the Singapore military where post-exposure oseltamivir ring chemoprophylaxis (75 mg daily for 10 days) was administered. The entire cohort was screened by RT-PCR (with HA gene primers) using nasopharyngeal swabs three times a week. Three blood samples were taken for haemagglutination inhibition testing - at the start of outbreak, 2 weeks after completion of 10 day oseltamivir prophylaxis, and 3 weeks after the pandemic's peak in Singapore. Questionnaires were also administered to collect clinical symptoms.</p> <p>Results</p> <p>237 personnel were included for analysis. The overall infection rate of 2009 Influenza A (H1N1) during the three outbreaks was 11.4% (27/237). This included 11 index cases and 16 personnel (7.1%) who developed four-fold or higher rise in antibody titres during oseltamivir prophylaxis. Of these 16 personnel, 8 (3.5%) were symptomatic while the remaining 8 personnel (3.5%) were asymptomatic and tested negative on PCR. Post-cessation of prophylaxis, an additional 23 (12.1%) seroconverted. There was no significant difference in mean fold-rise in GMT between those who seroconverted during and post-prophylaxis (11.3 vs 11.7, p = 0.888). No allergic, neuropsychiatric or other severe side-effects were noted.</p> <p>Conclusions</p> <p>Post-exposure oseltamivir prophylaxis reduced the rate of infection during outbreaks, and did not substantially increase subsequent infection rates upon cessation. Asymptomatic infections occur during prophylaxis, which may confer protection against future infection. Post-exposure prophylaxis is effective as a measure in mitigating pandemic influenza outbreaks.</p

Contribution of Inelastic Rescatterring to B→ππ,KKˉB \to \pi \pi, K \bar{K} Decays

We discuss multichannel inelastic rescatterring effects in B decays into a pair $PP$ of pseudoscalar mesons ($PP = \pi \pi$ or $K\bar{K}$). In agreement with short-distance models it is assumed that initially $B$ meson decays dominantly into jet-like states composed of two flying-apart low-mass resonances $M_1 M_2$ which rescatter into $PP$. Since from all S-matrix elements $$ involving $PP$ only some ($i = M_1 M_2$) contribute to the final state rescatterring, the latter is treated as a correction only. The rescatterring of resonance pair $M_1 M_2$ into the final $PP$ state is assumed to proceed through Regge exchange. Although effects due to a single intermediate state $M_1 M_2$ are small, it is shown that the combined effect of all such states should be large. In particular, amplitudes of B decays into $K\bar{K}$ become significantly larger than those estimated through short-distance penguin diagrams, to the point of being comparable to the $B\to \pi \pi$ amplitudes.Comment: 25 LaTeX pages, 6 figures in one .ps fil

A clinical diagnostic model for predicting influenza among young adult military personnel with febrile respiratory illness in Singapore

10.1371/journal.pone.0017468PLoS ONE63

Lovastatin Modulates Glycogen Synthase Kinase-3β Pathway and Inhibits Mossy Fiber Sprouting after Pilocarpine-Induced Status Epilepticus

This study was undertaken to assay the effect of lovastatin on the glycogen synthase kinase-3 beta (GSK-3β) and collapsin responsive mediator protein-2 (CRMP-2) signaling pathway and mossy fiber sprouting (MFS) in epileptic rats. MFS in the dentate gyrus (DG) is an important feature of temporal lobe epilepsy (TLE) and is highly related to the severity and the frequency of spontaneous recurrent seizures. However, the molecular mechanism of MFS is mostly unknown. GSK-3β and CRMP-2 are the genes responsible for axonal growth and neuronal polarity in the hippocampus, therefore this pathway is a potential target to investigate MFS. Pilocarpine-induced status epilepticus animal model was taken as our researching material. Western blot, histological and electrophysiological techniques were used as the studying tools. The results showed that the expression level of GSK-3β and CRMP-2 were elevated after seizure induction, and the administration of lovastatin reversed this effect and significantly reduced the extent of MFS in both DG and CA3 region in the hippocampus. The alteration of expression level of GSK-3β and CRMP-2 after seizure induction proposes that GSK-3β and CRMP-2 are crucial for MFS and epiletogenesis. The fact that lovastatin reversed the expression level of GSK-3β and CRMP-2 indicated that GSK-3β and CRMP-2 are possible to be a novel mechanism of lovatstain to suppress MFS and revealed a new therapeutic target and researching direction for studying the mechanism of MFS and epileptogenesis

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm