RRP20, a componenet of the 90S preribosome, is required for pre-18S rRNA processing in Saccharomyces cerevisiae

A strain of Saccharomyces cerevisiae, defective in small subunit ribosomal RNA processing, has a mutation in YOR145c ORF that converts Gly235 to Asp. Yor145c is a nucleolar protein required for cell viability and has been reported recently to be present in 90S pre-ribosomal particles. The Gly235Asp mutation in YOR145c is found in a KH-type RNA-binding domain and causes a marked deficiency in 18S rRNA production. Detailed studies by northern blotting and primer extension analyses show that the mutant strain impairs the early pre-rRNA processing cleavage essentially at sites A1 and A2, leading to accumulation of a 22S dead-end processing product that is found in only a few rRNA processing mutants. Furthermore, U3, U14, snR10 and snR30 snoRNAs, involved in early pre-rRNA cleavages, are not destabilized by the YOR145c mutation. As the protein encoded by YOR145c is found in pre-ribosomal particles and the mutant strain is defective in ribosomal RNA processing, we have renamed it as RRP20

Using Forecast and Observed Weather Data to Assess Performance of Forecast Products in Identifying Heat Waves and Estimating Heat Wave Effects on Mortality

Background: Heat wave and health warning systems are activated based on forecasts of health-threatening hot weather. Objective: We estimated heat–mortality associations based on forecast and observed weather data in Detroit, Michigan, and compared the accuracy of forecast products for predicting heat waves. Methods: We derived and compared apparent temperature (AT) and heat wave days (with heat waves defined as ≥ 2 days of daily mean AT ≥ 95th percentile of warm-season average) from weather observations and six different forecast products. We used Poisson regression with and without adjustment for ozone and/or PM10 (particulate matter with aerodynamic diameter ≤ 10 μm) to estimate and compare associations of daily all-cause mortality with observed and predicted AT and heat wave days. Results: The 1-day-ahead forecast of a local operational product, Revised Digital Forecast, had about half the number of false positives compared with all other forecasts. On average, controlling for heat waves, days with observed AT = 25.3°C were associated with 3.5% higher mortality (95% CI: –1.6, 8.8%) than days with AT = 8.5°C. Observed heat wave days were associated with 6.2% higher mortality (95% CI: –0.4, 13.2%) than non–heat wave days. The accuracy of predictions varied, but associations between mortality and forecast heat generally tended to overestimate heat effects, whereas associations with forecast heat waves tended to underestimate heat wave effects, relative to associations based on observed weather metrics. Conclusions: Our findings suggest that incorporating knowledge of local conditions may improve the accuracy of predictions used to activate heat wave and health warning systems. Citation: Zhang K, Chen YH, Schwartz JD, Rood RB, O’Neill MS. 2014. Using forecast and observed weather data to assess performance of forecast products in identifying heat waves and estimating heat wave effects on mortality. Environ Health Perspect 122:912–918; http://dx.doi.org/10.1289/ehp.130685

Skeletal Muscle Lacking the Extreme C-Terminal SH3 Domain of Nebulin Exhibits Heightened Vulnerability to Eccentric Contraction-Induced Injury

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A novel approach to Isoscaling: the role of the order parameter m = (N-Z)/A

Isoscaling is derived within a recently proposed modified Fisher model where the free energy near the critical point is described by the Landau O(m^6) theory. In this model m = (N-Z)/A is the order parameter, a consequence of (one of) the symmetries of the nuclear Hamiltonian. Within this framework we show that isoscaling depends mainly on this order parameter through the 'external (conjugate) field' H. The external field is just given by the difference in chemical potentials of the neutrons and protons of the two sources. To distinguish from previously employed isoscaling relationships, this approach is dubbed: m - scaling. We discuss the relationship between this framework and the standard isoscaling formalism and point out some substantial differences in interpretation of experimental results which might result. These should be investigated further both theoretically and experimentally.Comment: 14 pages, 5 figure

'The difference in determinants of Chlamydia trachomatis and Mycoplasma genitalium in a sample of young Australian women.'

BACKGROUND Differences in the determinants of Chlamydia trachomatis ('chlamydia') and Mycoplasma genitalium (MG) genital infection in women are not well understood. METHODS A cohort study of 16 to 25 year old Australian women recruited from primary health care clinics, aimed to determine chlamydia and MG prevalence and incidence. Vaginal swabs collected at recruitment were used to measure chlamydia and MG prevalence, organism-load and chlamydia-serovar a cross-sectional analysis undertaken on the baseline results is presented here. RESULTS Of 1116 participants, chlamydia prevalence was 4.9% (95% CI: 2.9, 7.0) (n = 55) and MG prevalence was 2.4% (95% CI: 1.5, 3.3) (n = 27). Differences in the determinants were found - chlamydia not MG, was associated with younger age [AOR:0.9 (95% CI: 0.8, 1.0)] and recent antibiotic use [AOR:0.4 (95% CI: 0.2, 1.0)], and MG not chlamydia was associated with symptoms [AOR:2.1 (95% CI: 1.1, 4.0)]. Having two or more partners in last 12 months was more strongly associated with chlamydia [AOR:6.4 (95% CI: 3.6, 11.3)] than MG [AOR:2.2 (95% CI: 1.0, 4.6)] but unprotected sex with three or more partners was less strongly associated with chlamydia [AOR:3.1 (95%CI: 1.0, 9.5)] than MG [AOR:16.6 (95%CI: 2.0, 138.0)]. Median organism load for MG was 100 times lower (5.7 × 104/swab) than chlamydia (5.6 × 10⁶/swab) (p < 0.01) and not associated with age or symptoms for chlamydia or MG. CONCLUSIONS These results demonstrate significant chlamydia and MG prevalence in Australian women, and suggest that the differences in strengths of association between numbers of sexual partners and unprotected sex and chlamydia and MG might be due to differences in the transmission dynamics between these infections.This project was funded by the Commonwealth of Australia, as part of a National Chlamydia Pilot program that is currently running to test the effectiveness of a number of models for chlamydia testing in Australia. This project will assist in developing possible recommendations for a National Chlamydia Program. The analysis of MG was funded by the National Health and Research Council (research grant number 509144)

DNA-based Diagnosis of Uncharacterized Inherited Macrothrombocytopenias Using Next-generation Sequencing Technology with a Candidate Gene Array

Inherited macrothrombocytopenias comprise a heterogeneous group of inherited platelet disorders that are characterized by large platelets, thrombocytopenia and bleeding tendencies in affected individuals. Diagnostic platforms have traditionally involved a battery of complex phenotypic tests that often fail to reach a diagnosis. Next-generation sequencing lacks the pre-analytical and analytical shortcoming of these tests and provides an attractive alternate diagnostic approach. Our group has developed a candidate gene array targeting genes known to affect platelet function and tested it in a large cohort of Australasian patients with presumed platelet function disorders, particularly macrothrombocytopenia. This array identified causative variants in a significant portion of patients with uncharacterized platelet disorders, including transcription factor mutations that cannot easily be diagnosed with standard platelet phenotyping procedures. We propose that targeted genotypic screening can identify the genetic basis of platelet function defects and has the potential to be developed into a powerful clinical platform to help clinicians diagnose these rare disorders

The MBD7 complex promotes expression of methylated transgenes without significantly altering their methylation status.

DNA methylation is associated with gene silencing in eukaryotic organisms. Although pathways controlling the establishment, maintenance and removal of DNA methylation are known, relatively little is understood about how DNA methylation influences gene expression. Here we identified a METHYL-CpG-BINDING DOMAIN 7 (MBD7) complex in Arabidopsis thaliana that suppresses the transcriptional silencing of two LUCIFERASE (LUC) reporters via a mechanism that is largely downstream of DNA methylation. Although mutations in components of the MBD7 complex resulted in modest increases in DNA methylation concomitant with decreased LUC expression, we found that these hyper-methylation and gene expression phenotypes can be genetically uncoupled. This finding, along with genome-wide profiling experiments showing minimal changes in DNA methylation upon disruption of the MBD7 complex, places the MBD7 complex amongst a small number of factors acting downstream of DNA methylation. This complex, however, is unique as it functions to suppress, rather than enforce, DNA methylation-mediated gene silencing

Fermi-edge singularities in linear and non-linear ultrafast spectroscopy

We discuss Fermi-edge singularity effects on the linear and nonlinear transient response of an electron gas in a doped semiconductor. We use a bosonization scheme to describe the low energy excitations, which allows to compute the time and temperature dependence of the response functions. Coherent control of the energy absorption at resonance is analyzed in the linear regime. It is shown that a phase-shift appears in the coherent control oscillations, which is not present in the excitonic case. The nonlinear response is calculated analytically and used to predict that four wave-mixing experiments would present a Fermi-edge singularity when the exciting energy is varied. A new dephasing mechanism is predicted in doped samples that depends linearly on temperature and is produced by the low-energy bosonic excitations in the conduction band.Comment: long version; 9 pages, 4 figure