Molecular evidence for increased regulatory conservation during metamorphosis, and against deleterious cascading effects of hybrid breakdown in Drosophila

<p>Abstract</p> <p>Background</p> <p>Speculation regarding the importance of changes in gene regulation in determining major phylogenetic patterns continues to accrue, despite a lack of broad-scale comparative studies examining how patterns of gene expression vary during development. Comparative transcriptional profiling of adult interspecific hybrids and their parental species has uncovered widespread divergence of the mechanisms controlling gene regulation, revealing incompatibilities that are masked in comparisons between the pure species. However, this has prompted the suggestion that misexpression in adult hybrids results from the downstream cascading effects of a subset of genes improperly regulated in early development.</p> <p>Results</p> <p>We sought to determine how gene expression diverges over development, as well as test the cascade hypothesis, by profiling expression in males of <it>Drosophila melanogaster</it>, <it>D. sechellia</it>, and <it>D. simulans</it>, as well as the <it>D. simulans </it>(♀) × <it>D. sechellia </it>(♂) male F1 hybrids, at four different developmental time points (3rd instar larval, early pupal, late pupal, and newly-emerged adult). Contrary to the cascade model of misexpression, we find that there is considerable stage-specific autonomy of regulatory breakdown in hybrids, with the larval and adult stages showing significantly more hybrid misexpression as compared to the pupal stage. However, comparisons between pure species indicate that genes expressed during earlier stages of development tend to be more conserved in terms of their level of expression than those expressed during later stages, suggesting that while Von Baer's famous law applies at both the level of nucleotide sequence and expression, it may not apply necessarily to the underlying overall regulatory network, which appears to diverge over the course of ontogeny and which can only be ascertained by combining divergent genomes in species hybrids.</p> <p>Conclusion</p> <p>Our results suggest that complex integration of regulatory circuits during morphogenesis may lead to it being more refractory to divergence of underlying gene regulatory mechanisms - more than that suggested by the conservation of gene expression levels between species during earlier stages. This provides support for a 'developmental hourglass' model of divergence of gene expression in <it>Drosophila </it>resulting in a highly conserved pupal stage.</p

Short-term salivary acetaldehyde increase due to direct exposure to alcoholic beverages as an additional cancer risk factor beyond ethanol metabolism

<p>Abstract</p> <p>Background</p> <p>An increasing body of evidence now implicates acetaldehyde as a major underlying factor for the carcinogenicity of alcoholic beverages and especially for oesophageal and oral cancer. Acetaldehyde associated with alcohol consumption is regarded as 'carcinogenic to humans' (IARC Group 1), with sufficient evidence available for the oesophagus, head and neck as sites of carcinogenicity. At present, research into the mechanistic aspects of acetaldehyde-related oral cancer has been focused on salivary acetaldehyde that is formed either from ethanol metabolism in the epithelia or from microbial oxidation of ethanol by the oral microflora. This study was conducted to evaluate the role of the acetaldehyde that is found as a component of alcoholic beverages as an additional factor in the aetiology of oral cancer.</p> <p>Methods</p> <p>Salivary acetaldehyde levels were determined in the context of sensory analysis of different alcoholic beverages (beer, cider, wine, sherry, vodka, calvados, grape marc spirit, tequila, cherry spirit), without swallowing, to exclude systemic ethanol metabolism.</p> <p>Results</p> <p>The rinsing of the mouth for 30 seconds with an alcoholic beverage is able to increase salivary acetaldehyde above levels previously judged to be carcinogenic in vitro, with levels up to 1000 μM in cases of beverages with extreme acetaldehyde content. In general, the highest salivary acetaldehyde concentration was found in all cases in the saliva 30 sec after using the beverages (average 353 μM). The average concentration then decreased at the 2-min (156 μM), 5-min (76 μM) and 10-min (40 μM) sampling points. The salivary acetaldehyde concentration depends primarily on the direct ingestion of acetaldehyde contained in the beverages at the 30-sec sampling, while the influence of the metabolic formation from ethanol becomes the major factor at the 2-min sampling point.</p> <p>Conclusions</p> <p>This study offers a plausible mechanism to explain the increased risk for oral cancer associated with high acetaldehyde concentrations in certain beverages.</p

The Cell Cycle Time of CD8+ T Cells Responding In Vivo Is Controlled by the Type of Antigenic Stimulus

A hallmark of cells comprising the mammalian adaptive immune system is the requirement for these rare naïve T (and B) lymphocytes directed to a specific microorganism to undergo proliferative expansion upon first encounter with this antigen. In the case of naïve CD8+ T cells the ability of these rare quiescent lymphocytes to rapidly activate and expand into effector T cells in numbers sufficient to control viral and certain bacterial infections can be essential for survival. In this report we examined the activation, cell cycle time and initial proliferative response of naïve murine CD8+ T cells responding in vivo to Influenza and Vaccinia virus infection or vaccination with viral antigens. Remarkably, we observed that CD8+ T cells could divide and proliferate with an initial cell division time of as short as 2 hours. The initial cell cycle time of responding CD8+ T cells is not fixed but is controlled by the antigenic stimulus provided by the APC in vivo. Initial cell cycle time influences the rate of T cell expansion and the numbers of effector T cells subsequently accumulating at the site of infection. The T cell cycle time varies with duration of the G1 phase of the cell cycle. The duration of G1 is inversely correlated with the phosphorylation state of the retinoblastoma (Rb) protein in the responding T cells. The implication of these findings for the development of adaptive immune responses and the regulation of cell cycle in higher eukaryotic cells is discussed

Is alcohol consumption a risk factor for prostate cancer? A systematic review and meta-analysis.

Background: Research on a possible causal association between alcohol consumption and risk of prostate cancer is inconclusive. Recent studies on associations between alcohol consumption and other health outcomes suggest these are influenced by drinker misclassification errors and other study quality characteristics. The influence of these factors on estimates of the relationship between alcohol consumption and prostate cancer has not been previously investigated. Methods: PubMed and Web of Science searches were made for case–control and cohort studies of alcohol consumption and prostate cancer morbidity and mortality (ICD–10: C61) up to December 2014. Studies were coded for drinker misclassification errors, quality of alcohol measures, extent of control for confounding and other study characteristics. Mixed models were used to estimate relative risk (RR) of morbidity or mortality from prostate cancer due to alcohol consumption with study level controls for selection bias and confounding. Results: A total of 340 studies were identified of which 27 satisfied inclusion criteria providing 126 estimates for different alcohol exposures. Adjusted RR estimates indicated a significantly increased risk of prostate cancer among low (RR = 1.08, P 1.3, <24 g per day). This relationship is stronger in the relatively few studies free of former drinker misclassification error. Given the high prevalence of prostate cancer in the developed world, the public health implications of these findings are significant. Prostate cancer may need to be incorporated into future estimates of the burden of disease alongside other cancers (e.g. breast, oesophagus, colon, liver) and be integrated into public health strategies for reducing alcohol related disease

Anatomy of the sign-problem in heavy-dense QCD

QCD at finite densities of heavy quarks is investigated using the density-of-states method. The phase factor expectation value of the quark determinant is calculated to unprecedented precision as a function of the chemical potential. Results are validated using those from a reweighting approach where the latter can produce a significant signalto-noise ratio. We confirm the particle–hole symmetry at low temperatures, find a strong sign problem at intermediate values of the chemical potential, and an inverse Silver Blaze feature for chemical potentials close to the onset value: here, the phase-quenched theory underestimates the density of the full theory

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level

Search for the direct production of charginos and neutralinos in final states with tau leptons in √s=13 TeV collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with at least two hadronically decaying tau leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of 36.1 fb−1, recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13TeV.Nosignificant deviation from the expected Standard Model background is observed. Limits are derived in scenarios of ˜χ+1 ˜χ−1 pair production and of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 production in simplified models where the neutralinos and charginos decay solely via intermediate left-handed staus and tau sneutrinos, and the mass of the ˜ τL state is set to be halfway between the masses of the ˜χ±1 and the ˜χ01. Chargino masses up to 630 GeV are excluded at 95% confidence level in the scenario of direct production of ˜χ+1 ˜χ−1 for a massless ˜χ01. Common ˜χ±1 and ˜χ02 masses up to 760 GeV are excluded in the case of production of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 assuming a massless ˜χ01. Exclusion limits for additional benchmark scenarios with large and small mass-splitting between the ˜χ±1 and the ˜χ01 are also studied by varying the ˜ τL mass between the masses of the ˜χ±1 and the ˜χ01

Measurement of differential cross sections and W + /W − cross-section ratios for W boson production in association with jets at √s =8 TeV with the ATLAS detector

This paper presents a measurement of the W boson production cross section and the W + /W − cross-section ratio, both in association with jets, in proton--proton collisions at s √ =8 TeV with the ATLAS experiment at the Large Hadron Collider. The measurement is performed in final states containing one electron and missing transverse momentum using data corresponding to an integrated luminosity of 20.2 fb −1 . Differential cross sections for events with one or two jets are presented for a range of observables, including jet transverse momenta and rapidities, the scalar sum of transverse momenta of the visible particles and the missing transverse momentum in the event, and the transverse momentum of the W boson. For a subset of the observables, the differential cross sections of positively and negatively charged W bosons are measured separately. In the cross-section ratio of W + /W − the dominant systematic uncertainties cancel out, improving the measurement precision by up to a factor of nine. The observables and ratios selected for this paper provide valuable input for the up quark, down quark, and gluon parton distribution functions of the proto

Study of ordered hadron chains with the ATLAS detector

The analysis of the momentum difference between charged hadrons in high-energy proton-proton collisions is performed in order to study coherent particle production. The observed correlation pattern agrees with a model of a helical QCD string fragmenting into a chain of ground-state hadrons. A threshold momentum difference in the production of adjacent pairs of charged hadrons is observed, in agreement with model predictions. The presence of low-mass hadron chains also explains the emergence of charge-combination-dependent two-particle correlations commonly attributed to Bose-Einstein interference. The data sample consists of 190 μb−1 of minimum-bias events collected with proton-proton collisions at a center-of-mass energy √s=7 TeV in the early low-luminosity data taking with the ATLAS detector at the LHC

Performance of missing transverse momentum reconstruction with the ATLAS detector using proton–proton collisions at √s = 13 TeV

The performance of the missing transverse momentum (EmissT) reconstruction with the ATLAS detector is evaluated using data collected in proton–proton collisions at the LHC at a centre-of-mass energy of 13 TeV in 2015. To reconstruct EmissT, fully calibrated electrons, muons, photons, hadronically decaying τ -leptons, and jets reconstructed from calorimeter energy deposits and charged-particle tracks are used. These are combined with the soft hadronic activity measured by reconstructed charged-particle tracks not associated with the hard objects. Possible double counting of contributions from reconstructed charged-particle tracks from the inner detector, energy deposits in the calorimeter, and reconstructed muons from the muon spectrometer is avoided by applying a signal ambiguity resolution procedure which rejects already used signals when combining the various EmissT contributions. The individual terms as well as the overall reconstructed EmissT are evaluated with various performance metrics for scale (linearity), resolution, and sensitivity to the data-taking conditions. The method developed to determine the systematic uncertainties of the EmissT scale and resolution is discussed. Results are shown based on the full 2015 data sample corresponding to an integrated luminosity of 3.2 fb−1