Combinatorial control of temporal gene expression in the Drosophila wing by enhancers and core promoters

Abstract Background The transformation of a developing epithelium into an adult structure is a complex process, which often involves coordinated changes in cell proliferation, metabolism, adhesion, and shape. To identify genetic mechanisms that control epithelial differentiation, we analyzed the temporal patterns of gene expression during metamorphosis of the Drosophila wing. Results We found that a striking number of genes, approximately 50% of the Drosophila transcriptome, exhibited changes in expression during a time course of wing development. While cis-acting enhancer sequences clearly correlated with these changes, a stronger correlation was discovered between core-promoter types and the dynamic patterns of gene expression within this differentiating tissue. In support of the hypothesis that core-promoter type influences the dynamics of expression, expression levels of several TATA-box binding protein associated factors (TAFs) and other core promoter-associated components changed during this developmental time course, and a testes-specific TAF (tTAF) played a critical role in timing cellular differentiation within the wing. Conclusions Our results suggest that the combinatorial control of gene expression via cis-acting enhancer sequences and core-promoter types, determine the complex changes in gene expression that drive morphogenesis and terminal differentiation of the Drosophila wing epithelium.http://deepblue.lib.umich.edu/bitstream/2027.42/112935/1/12864_2012_Article_4965.pd

The gene SMART study: method, study design, and preliminary findings

The gene SMART (genes and the Skeletal Muscle Adaptive Response to Training) Study aims to identify genetic variants that predict the response to both a single session of High-Intensity Interval Exercise (HIIE) and to four weeks of High-Intensity Interval Training (HIIT). While the training and testing centre is located at Victoria University, Melbourne, three other centres have been launched at Bond University, Queensland University of Technology, Australia, and the University of Brighton, UK. Currently 39 participants have already completed the study and the overall aim is to recruit 200 moderately-trained, healthy Caucasians participants (all males 18–45 y, BMI \u3c 30). Participants will undergo exercise testing and exercise training by an identical exercise program. Dietary habits will be assessed by questionnaire and dietitian consultation. Activity history is assessed by questionnaire and current activity level is assessed by an activity monitor. Skeletal muscle biopsies and blood samples will be collected before, immediately after and 3 h post HIIE, with the fourth resting biopsy and blood sample taken after four weeks of supervised HIIT (3 training sessions per week). Each session consists of eight to fourteen 2-min intervals performed at the pre-training lactate threshold (LT) power plus 40 to 70% of the difference between pre-training lactate threshold (LT) and peak aerobic power (Wpeak). A number of muscle and blood analyses will be performed, including (but not limited to) genotyping, mitochondrial respiration, transcriptomics, protein expression analyses, and enzyme activity. The participants serve as their own controls. Even though the gene SMART study is tightly controlled, our preliminary findings still indicate considerable individual variability in both performance (in-vivo) and muscle (in-situ) adaptations to similar training. More participants are required to allow us to better investigate potential underlying genetic and molecular mechanisms responsible for this individual variability

Discovering Argumentative Patterns in Energy Polylogues: A Macroscope for Argument Mining

A macroscope is proposed and tested here for the discovery of the unique argumentative footprint that characterizes how a collective (e.g., group, online community) manages differences and pursues disagreement through argument in a polylogue. The macroscope addresses broader analytic problems posed by various conceptualizations of large-scale argument, such as fields, spheres, communities, and institutions. The design incorporates a two-tier methodology for detecting argument patterns of the arguments performed in arguing by an interactive collective that produces views, or topographies, of the ways that issues are generated in the making and defending of standpoints. The design premises for the macroscope build on insights about argument patterns from pragma-dialectical theory by incorporating research and theory on disagreement management and the Argumentum Model of Topics. The design reconceptualizes prototypical and stereotypical argument patterns for characterizing large-scale argumentation. A prototype of the macroscope is tested on data drawn from six threads about oil-drilling and fracking from the subreddit Changemyview. The implementation suggests the efficacy of the macroscope’s design and potential for identifying what communities make controversial and how the disagreement space in a polylogue is managed through stereotypical argument patterns in terms of claims/premises, inferential relations, and presentational devices

A genomic storm in critically injured humans

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes

Phosphorothioate antisense oligonucleotides induce the formation of nuclear bodies

Antisense oligonucleotides are powerful tools for the in vivo regulation of gene expression. We have characterized the intracellular distribution of fluorescently tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under conditions in which PS-ONs have the potential to display antisense activity. Under these conditions PS-ONs predominantly localized to the cell nucleus where they accumulated in 20-30 bright spherical foci designated phosphorothioate bodies (PS bodies), which were set against a diffuse nucleoplasmic population excluding nucleoli. PS bodies are nuclear structures that formed in cells after PS-ON delivery by transfection agents or microinjection but were observed irrespectively of antisense activity or sequence. Ultrastructurally, PS bodies corresponded to electron-dense structures of 150-300 nm diameter and resembled nuclear bodies that were found with lower frequency in cells lacking PS-ONs. The environment of a living cell was required for the de novo formation of PS bodies, which occurred within minutes after the introduction of PS-ONs. PS bodies were stable entities that underwent noticeable reorganization only during mitosis. Upon exit from mitosis, PS bodies were assembled de novo from diffuse PS-ON pools in the daughter nuclei. In situ fractionation demonstrated an association of PS-ONs with the nuclear matrix. Taken together, our data provide evidence for the formation of a nuclear body in cells after introduction of phosphorothioate oligodeoxynucleotides

Measurement of the energy response of the ATLAS calorimeter to charged pions from W±→ τ±(→ π±ντ) ντ events in Run 2 data

The energy response of the ATLAS calorimeter is measured for single charged pions with transverse momentum in the range 10 < pT< 300 GeV. The measurement is performed using 139 fb - 1 of LHC proton–proton collision data at s=13 TeV taken in Run 2 by the ATLAS detector. Charged pions originating from τ-lepton decays are used to provide a sample of high-pT isolated particles, where the composition is known, to test an energy regime that has not previously been probed by in situ single-particle measurements. The calorimeter response to single-pions is observed to be overestimated by ∼ 2 % across a large part of the pT spectrum in the central region and underestimated by ∼ 4 % in the endcaps in the ATLAS simulation. The uncertainties in the measurements are ≲ 1 % for 15 < pT< 185 GeV in the central region. To investigate the source of the discrepancies, the width of the distribution of the ratio of calorimeter energy to track momentum, the energies per layer and response in the hadronic calorimeter are also compared between data and simulation

Measurement of the energy asymmetry in tt¯ j production at 13 TeV with the ATLAS experiment and interpretation in the SMEFT framework

A measurement of the energy asymmetry in jet-associated top-quark pair production is presented using 139fb-1 of data collected by the ATLAS detector at the Large Hadron Collider during pp collisions at s=13TeV. The observable measures the different probability of top and antitop quarks to have the higher energy as a function of the jet scattering angle with respect to the beam axis. The energy asymmetry is measured in the semileptonic tt¯ decay channel, and the hadronically decaying top quark must have transverse momentum above 350GeV. The results are corrected for detector effects to particle level in three bins of the scattering angle of the associated jet. The measurement agrees with the SM prediction at next-to-leading-order accuracy in quantum chromodynamics in all three bins. In the bin with the largest expected asymmetry, where the jet is emitted perpendicular to the beam, the energy asymmetry is measured to be - 0.043 ± 0.020 , in agreement with the SM prediction of - 0.037 ± 0.003. Interpreting this result in the framework of the Standard Model effective field theory (SMEFT), it is shown that the energy asymmetry is sensitive to the top-quark chirality in four-quark operators and is therefore a valuable new observable in global SMEFT fits

Searches for lepton-flavour-violating decays of the Higgs boson into eτ and μτ in \sqrt{s} = 13 TeV pp collisions with the ATLAS detector

Abstract This paper presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ, performed using data collected with the ATLAS detector at the LHC. The searches are based on a data sample of proton-proton collisions at a centre-of-mass energy s $$\sqrt{s}$$ = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. Leptonic (τ → ℓνℓντ) and hadronic (τ → hadrons ντ) decays of the τ-lepton are considered. Two background estimation techniques are employed: the MC-template method, based on data-corrected simulation samples, and the Symmetry method, based on exploiting the symmetry between electrons and muons in the Standard Model backgrounds. No significant excess of events is observed and the results are interpreted as upper limits on lepton-flavour-violating branching ratios of the Higgs boson. The observed (expected) upper limits set on the branching ratios at 95% confidence level, B $$\mathcal{B}$$ (H → eτ) < 0.20% (0.12%) and B $$\mathcal{B}$$ (H → μτ ) < 0.18% (0.09%), are obtained with the MC-template method from a simultaneous measurement of potential H → eτ and H → μτ signals. The best-fit branching ratio difference, B $$\mathcal{B}$$ (H → μτ) → B $$\mathcal{B}$$ (H → eτ), measured with the Symmetry method in the channel where the τ-lepton decays to leptons, is (0.25 ± 0.10)%, compatible with a value of zero within 2.5σ

Modelling and computational improvements to the simulation of single vector-boson plus jet processes for the ATLAS experiment

This paper presents updated Monte Carlo configurations used to model the production of single electroweak vector bosons (W, Z/γ∗) in association with jets in proton-proton collisions for the ATLAS experiment at the Large Hadron Collider. Improvements pertaining to the electroweak input scheme, parton-shower splitting kernels and scale-setting scheme are shown for multi-jet merged configurations accurate to next-to-leading order in the strong and electroweak couplings. The computational resources required for these set-ups are assessed, and approximations are introduced resulting in a factor three reduction of the per-event CPU time without affecting the physics modelling performance. Continuous statistical enhancement techniques are introduced by ATLAS in order to populate low cross-section regions of phase space and are shown to match or exceed the generated effective luminosity. This, together with the lower per-event CPU time, results in a 50% reduction in the required computing resources compared to a legacy set-up previously used by the ATLAS collaboration. The set-ups described in this paper will be used for future ATLAS analyses and lay the foundation for the next generation of Monte Carlo predictions for single vector-boson plus jets production. [Figure not available: see fulltext.]