FASTER MT: Isolation of Pure Populations of a and α Ascospores from Saccharomyces cerevisiae

The budding yeast Saccharomyces cerevisiae has many traits that make it useful for studies of quantitative inheritance. Genome-wide association studies and bulk segregant analyses often serve as first steps toward the identification of quantitative trait loci. These approaches benefit from having large numbers of ascospores pooled by mating type without contamination by vegetative cells. To this end, we inserted a gene encoding red fluorescent protein into the MATa locus. Red fluorescent protein expression caused MATa and a/α diploid vegetative cells and MATa ascospores to fluoresce; MATα cells without the gene did not fluoresce. Heterozygous diploids segregated fluorescent and nonfluorescent ascospores 2:2 in tetrads and bulk populations. The two populations of spores were separable by fluorescence-activated cell sorting with little cross contamination or contamination with diploid vegetative cells. This approach, which we call Fluorescent Ascospore Technique for Efficient Recovery of Mating Type (FASTER MT), should be applicable to laboratory, industrial, and undomesticated, strains

Comparison of branded rugby headguards on their effectiveness in reducing impact on the head

Aim: To compare the available brands of rugby headguards and evaluate their impact attenuation properties at various locations on the cranium, with regard to concussion prevention.Methods: Seven different branded headguards were fitted onto a rigid headform and drop-tested in three different positions. An accelerometer measured the linear acceleration the headform experienced on impact with the ground. Each test involved dropping the headform from a height that generated 103.8 g on average when bare, which is the closest acceleration to the upper limit of the concussion threshold of 100 g. A mean peak acceleration for each drop position was calculated and compared with the bare baseline measurement.Results: Each headguard demonstrated a significant decrease in the mean peak acceleration from the baseline value (all p≤0.01). Overall the Canterbury Ventilator was the most effective headguard, decreasing the impact force on average by 47%. The least effective was the XBlades Elite headguard, averaging a force reduction of 27%. In five of the seven headguards, the right side of the headwear was the most effective at reducing impact force.Conclusion: Overall, the results indicate that it would be beneficial to wear a headguard during rugby in order to reduce the impact forces involved in head collisions. There was also a clear difference in performance between the tested brands, establishing the Canterbury headguard as the most effective. However, only one model of headguard from each brand was tested, so further research evaluating all other models should be considered.</p

The Risk of Exposure to Diagnostic Ultrasound in Postnatal Subjects

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135382/1/jum2008274565.pd

Absolute Paleointensity Study of Miocene Tiva Canyon Tuff, Yucca Mountain, Nevada: Role of Fine‐Particle Grain‐Size Variations

Fine‐grained, Ti‐poor titanomagnetite in the ~12.7 Ma Tiva Canyon (TC) Tuff systematically increases in grain size from superparamagnetic (SP) at the flow base to single domain (SD) at a few meters height. This allows us to examine the role of grain‐size variation on paleointensity, within the transition from SP to stable SD. We present magnetic properties from two previously unreported sections of the TC Tuff, as well as Thellier‐type paleointensity estimates from the lowermost ~7.0 m of the flow. Magnetic hysteresis, frequency‐dependent susceptibility, and thermomagnetic data show that sample grain‐size distribution is dominated by SP in the lower ~3.6 m, transitioning upwards to mostly stable SD. Paleointensity results are closely tied to stratigraphic height and to magnetic properties linked to domain state. SD samples have consistent absolute paleointensity values of 28.5 ± 1.94 μT (VADM of 51.3 ZAm2) and behaved ideally during paleointensity experiments. The samples including a significant SP fraction have consistently higher paleointensities and less ideal behavior but would likely pass many traditional quality‐control tests. We interpret the SD remanence to be a primary thermal remanent magnetization but discuss the possibility of a partial thermal‐chemical remanent magnetization if microcrystal growth continued at T \u3c Tc and/or the section is affected by post‐emplacement vapor‐phase alteration. The link between paleointensity and domain state is stronger than correlations with water content or other evidence of alteration and suggests that the presence of a significant SP population may adversely impact paleointensity results, even in the presence of a stable SD fraction

From CFTR biology toward combinatorial pharmacotherapy:expanded classification of cystic fibrosis mutations

More than 2000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been described that confer a range of molecular cell biological and functional phenotypes. Most of these mutations lead to compromised anion conductance at the apical plasma membrane of secretory epithelia and cause cystic fibrosis (CF) with variable disease severity. Based on the molecular phenotypic complexity of CFTR mutants and their susceptibility to pharmacotherapy, it has been recognized that mutations may impose combinatorial defects in CFTR channel biology. This notion led to the conclusion that the combination of pharmacotherapies addressing single defects (e.g., transcription, translation, folding, and/or gating) may show improved clinical benefit over available low-efficacy monotherapies. Indeed, recent phase 3 clinical trials combining ivacaftor (a gating potentiator) and lumacaftor (a folding corrector) have proven efficacious in CF patients harboring the most common mutation (deletion of residue F508, ΔF508, or Phe508del). This drug combination was recently approved by the U.S. Food and Drug Administration for patients homozygous for ΔF508. Emerging studies of the structural, cell biological, and functional defects caused by rare mutations provide a new framework that reveals a mixture of deficiencies in different CFTR alleles. Establishment of a set of combinatorial categories of the previously defined basic defects in CF alleles will aid the design of even more efficacious therapeutic interventions for CF patients

MutLα heterodimers modify the molecular phenotype of Friedreich ataxia

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. © 2014 Ezzatizadeh et al.This article has been made available through the Brunel Open Access Publishing Fund

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13