3,263 research outputs found
Quantitative insertion-site sequencing (QIseq) for high throughput phenotyping of transposon mutants
Genetic screening using random transposon insertions has been a powerful tool for uncovering biology in prokaryotes, where whole-genome saturating screens have been performed in multiple organisms. In eukaryotes, such screens have proven more problematic, in part because of the lack of a sensitive and robust system for identifying transposon insertion sites. We here describe quantitative insertion-site sequencing, or QIseq, which uses custom library preparation and Illumina sequencing technology and is able to identify insertion sites from both the 5' and 3' ends of the transposon, providing an inbuilt level of validation. The approach was developed using piggyBac mutants in the human malaria parasite Plasmodium falciparum but should be applicable to many other eukaryotic genomes. QIseq proved accurate, confirming known sites in >100 mutants, and sensitive, identifying and monitoring sites over a >10,000-fold dynamic range of sequence counts. Applying QIseq to uncloned parasites shortly after transfections revealed multiple insertions in mixed populations and suggests that >4000 independent mutants could be generated from relatively modest scales of transfection, providing a clear pathway to genome-scale screens in P. falciparum QIseq was also used to monitor the growth of pools of previously cloned mutants and reproducibly differentiated between deleterious and neutral mutations in competitive growth. Among the mutants with fitness defects was a mutant with a piggyBac insertion immediately upstream of the kelch protein K13 gene associated with artemisinin resistance, implying mutants in this gene may have competitive fitness costs. QIseq has the potential to enable the scale-up of piggyBac-mediated genetics across multiple eukaryotic systems
Low significance of evidence for black hole echoes in gravitational wave data
Recent detections of merging black holes allow observational tests of the
nature of these objects. In some proposed models, non-trivial structure at or
near the black hole horizon could lead to echo signals in gravitational wave
data. Recently, Abedi et al. claimed tentative evidence for repeating damped
echo signals following the gravitational-wave signals of the binary black hole
merger events recorded in the first observational period of the Advanced LIGO
interferometers. We reanalyse the same data, addressing some of the
shortcomings of their method using more background data and a modified
procedure. We find a reduced statistical significance for the claims of
evidence for echoes, calculating increased p-values for the null hypothesis of
echo-free noise. The reduced significance is entirely consistent with noise,
and so we conclude that the analysis of Abedi et al. does not provide any
observational evidence for the existence of Planck-scale structure at black
hole horizons.Comment: As accepted by Physical Review
SO(10) paths to dark matter
The grand-unification gauge group SO(10) contains matter parity as a discrete
subgroup. This symmetry could be at the origin of dark matter stability. The
properties of the dark matter candidates depend on the path along which SO(10)
is broken, in particular through Pati-Salam or left-right symmetric subgroups.
We systematically determine the non-supersymmetric dark matter scenarios that
can be realized along the various paths. We emphasize that the dark matter
candidates may have colored or electrically charged partners at low scale that
belong to the same SO(10) multiplet. These states, which in many cases are
important for co-annihilation, could be observed more easily than the dark
matter particle. We determine the structure of the tree-level and loop-induced
mass splittings between the dark matter candidate and their partners and
discuss the possible phenomenological implications.Comment: 44 pages; added references, to appear in PR
Comparison of Simulated Spatial Patterns Using Rain Gauge and Polarimetric-Radar-Based Precipitation Data in Catchment Hydrological Modeling
Evolutionary diversification of an ancient gene family (rhs) through C-terminal displacement
<p>Abstract</p> <p>Background</p> <p><it>Rhs </it>genes are prominent features of bacterial genomes that have previously been implicated in genomic rearrangements in <it>E. coli</it>. By comparing <it>rhs </it>repertoires across the Enterobacteriaceae, this study provides a robust explanation of <it>rhs </it>diversification and evolution, and a mechanistic model of how <it>rhs </it>diversity is gained and lost.</p> <p>Results</p> <p><it>Rhs </it>genes are ubiquitous and comprise six structurally distinct lineages within the Enterobacteriaceae. There is considerable intergenomic variation in <it>rhs </it>repertoire; for instance, in <it>Salmonella enterica</it>, <it>rhs </it>are restricted to mobile elements, while in <it>Escherichia coli </it>one <it>rhs </it>lineage has diversified through transposition as older lineages have been deleted. Overall, comparative genomics reveals frequent, independent gene gains and losses, as well as occasional lateral gene transfer, in different genera. Furthermore, we demonstrate that Rhs 'core' domains and variable C-termini are evolutionarily decoupled, and propose that <it>rhs </it>diversity is driven by homologous recombination with circular intermediates. Existing C-termini are displaced by laterally acquired alternatives, creating long arrays of dissociated 'tips' that characterize the appearance of <it>rhs </it>loci.</p> <p>Conclusion</p> <p><it>Rhs </it>repertoires are highly dynamic among Enterobacterial genomes, due to repeated gene gains and losses. In contrast, the primary structures of <it>Rhs </it>genes are evolutionarily conserved, indicating that <it>rhs </it>sequence diversity is driven, not by rapid mutation, but by the relatively slow evolution of novel core/tip combinations. Hence, we predict that a large pool of dissociated <it>rhs </it>C-terminal tips exists episomally and these are potentially transmitted across taxonomic boundaries.</p
Sources of Employment Growth by Occupation and Industry in Canada
Dans cet article, nous utilisons des donnĂ©es canadiennes des modĂšles d'intrants et d'extrants et des recensements de 1961, 1971 et 1981 afin d'identifier les causes des changements dans l'emploi durant chaque dĂ©cennie. Neuf causes de changement sont retenues. L'objectif de cet article est de dĂ©terminer les causes les plus importantes de la croissance de l'emploi agrĂ©gĂ© de mĂȘme que les facteurs expliquant la croissance plus rapide de l'emploi durant les annĂ©es 1970. De plus, les dĂ©terminants des dĂ©placements de l'emploi entre les secteurs de mĂȘme que des changements dans la composition de la main-dâĆuvre sont identifiĂ©s. Une attention particuliĂšre est prĂȘtĂ©e Ă l'importance des changements dans l'Ă©conomie de l'information.L'emploi agrĂ©gĂ© du secteur privĂ© a crĂ» de 35,3 % durant les annĂ©es 1970 alors que dans les annĂ©es 1960, la croissance ne fut que de 24,4 %. Le taux de croissance supĂ©rieur des annĂ©es 1970, qui survint malgrĂ© un dĂ©clin de celui de la demande finale, fut accompagnĂ© d'un dĂ©clin du taux de croissance de la productivitĂ© du travail. Le dĂ©clin du taux de croissance de la demande finale dans cette dĂ©cennie Ă©tait dĂ» Ă un ralentissement de celui des exportations.Les diffĂ©rences sectorielles du taux de croissance de l'emploi durant les annĂ©es 1960 peuvent ĂȘtre expliquĂ©es par des taux de croissance dans la productivitĂ© du travail diffĂ©rents entre les secteurs alors que durant les annĂ©es 1970, celles-ci furent plutĂŽt attribuables Ă des variations sectorielles du taux de croissance de la demande finale, et en particulier de la consommation. Durant ces deux dĂ©cennies, ces dĂ©terminants des diffĂ©rences sectorielles ont gĂ©nĂ©rĂ© une croissance supĂ©rieure dans le secteur des services.Par rapport Ă l'emploi total, la proportion des emplois reliĂ©s au domaine de l'information a crĂ» plus rapidement durant les annĂ©es 1960 que durant les annĂ©es 1970. La croissance de cette proportion est due en grande partie aux changements dans la composition de la main-dâĆuvre. Il y a cependant d'autres explications de ce dĂ©placement vers des emplois reliĂ©s au domaine de l'information. Parmi celles-ci, citons les taux de croissance sectoriels de l'emploi diffĂ©rents dus Ă des diffĂ©rences dans le taux de changement des heures travaillĂ©es, de la productivitĂ© du travail, de la demande finale et de la matrice d'intrants-extrants.This paper uses Canadian input-output and census data from 1961, 1971 and 1981 to decompose employment changes during each decade into nine sources. The goals are to identify: the main sources of growth in aggregate employment; factors which facilitated the more rapid rate of growth of employment in the 1970s; and some reasons for intersectoral shifts of employment and changes in the occupational composition of employment. We pay particular attention to the changing importance ofthe 'information economy '
Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy
Acknowledgments Blood biochemistry analysis and serum analysis were performed by the Easter Bush Pathology Department, University of Edinburgh. Animal husbandry was performed by Centre for Integrative Physiology bio-research restructure technical staff, University of Edinburgh. Assistance with intravenous injections was provided by Ian Coldicott (University of Sheffield) and Hannah Shorrock (University of Edinburgh). Human blood cDNA was a gift to GH from Kathy Evans, University of Edinburgh. Imaging was performed at the IMPACT imaging facility, University of Edinburgh, with technical assistance from Anisha Kubasik-Thayil. The authors would also like to thank Lyndsay Murray for technical discussions relating to qRT-PCR analysis. This work was supported by funding from the SMA Trust and the Anatomical Society (via grants to THG); the Euan MacDonald Centre for Motor Neurone Disease Research (via grants to THG and SHP); the Wellcome Trust (via grants to EJNG and THG); Muscular Dystrophy UK (via grants to THG and CGB); a Elphinstone Scholarship from the University of Aberdeen (to SHP); and The French Muscular Dystrophy Association (via grants to CM and JC).Peer reviewedPublisher PD
Particle Sensor Using Solidly Mounted Resonators
This paper describes the development of a novel particle sensing system employing zinc oxide based solidly mounted resonator (SMR) devices for the detection of airborne fine particles (i.e., PM2.5 and PM10). The system operates in a dual configuration in which two SMR devices are driven by Colpitts-type oscillators in a differential mode. Particles are detected by the frequency shift caused by the mass of particles present on one resonator with while the other acts as a reference channel. Experimental validation of the system was performed inside an environmental chamber using a dust generator with the particles of known size and concentration. A sensor sensitivity of 4.6 Hz per ÎŒg/m3 was demonstrated for the SMRs resonating at a frequency of 970 MHz. Our results demonstrate that the SMR-based system has the potential to be implemented in CMOS technology as a low-cost, miniature smart particle detector for the real-time monitoring of airborne particles
Risk of neuropsychiatric adverse events associated with varenicline:systematic review and meta-analysis
Objective To determine the risk of neuropsychiatric adverse events associated with use of varenicline compared with placebo in randomised controlled trials. Design Systematic review and meta-analysis comparing study effects using two summary estimates in fixed effects models, risk differences, and Peto odds ratios. Data sources Medline, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov. Eligibility criteria for selecting studies Randomised controlled trials with a placebo comparison group that reported on neuropsychiatric adverse events (depression, suicidal ideation, suicide attempt, suicide, insomnia, sleep disorders, abnormal dreams, somnolence, fatigue, anxiety) and death. Studies that did not involve human participants, did not use the maximum recommended dose of varenicline (1 mg twice daily), and were cross over trials were excluded. Results In the 39 randomised controlled trials (10â761 participants), there was no evidence of an increased risk of suicide or attempted suicide (odds ratio 1.67, 95% confidence interval 0.33 to 8.57), suicidal ideation (0.58, 0.28 to 1.20), depression (0.96, 0.75 to 1.22), irritability (0.98, 0.81 to 1.17), aggression (0.91, 0.52 to 1.59), or death (1.05, 0.47 to 2.38) in the varenicline users compared with placebo users. Varenicline was associated with an increased risk of sleep disorders (1.63, 1.29 to 2.07), insomnia (1.56, 1.36 to 1.78), abnormal dreams (2.38, 2.05 to 2.77), and fatigue (1.28, 1.06 to 1.55) but a reduced risk of anxiety (0.75, 0.61 to 0.93). Similar findings were observed when risk differences were reported. There was no evidence for a variation in depression and suicidal ideation by age group, sex, ethnicity, smoking status, presence or absence of psychiatric illness, and type of study sponsor (that is, pharmaceutical industry or other). Conclusions This meta-analysis found no evidence of an increased risk of suicide or attempted suicide, suicidal ideation, depression, or death with varenicline. These findings provide some reassurance for users and prescribers regarding the neuropsychiatric safety of varenicline. There was evidence that varenicline was associated with a higher risk of sleep problems such as insomnia and abnormal dreams. These side effects, however,are already well recognised. Systematic review registration PROSPERO 2014:CRD42014009224
- âŠ