Sleep differences in the UK between 1974 and 2015: Insights from detailed time diaries

It is often stated that sleep deprivation is on the rise, with work suggested as a main cause. However, the evidence for increasing sleep deprivation comes from surveys using habitual sleep questions. An alternative source of information regarding sleep behaviour is time‐use studies. This paper investigates changes in sleep time in the UK using the two British time‐use studies that allow measuring “time in bed not asleep” separately from “actual sleep time”. Based upon the studies presented here, people in the UK sleep today 43 min more than they did in the 1970s because they go to bed earlier (~30 min) and they wake up later (~15 min). The change in sleep duration is driven by night sleep and it is homogeneously distributed across the week. The former results apply to men and women alike, and to individuals of all ages and employment status, including employed individuals, the presumed major victims of the sleep deprivation epidemic and the 24/7 society. In fact, employed individuals have experienced a reduction in short sleeping of almost 4 percentage points, from 14.9% to 11.0%. There has also been a reduction of 15 percentage points in the amount of conflict between workers work time and their sleep time, as measured by the proportion of workers that do some work within their “ideal sleep window” (as defined by their own chronotype)

Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children

There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant in CDKN2A associated with the development of ALL at genome-wide significance (rs3731249, P=9.4 × 10(-23), odds ratio=2.23). Functional studies indicate that this hypomorphic variant results in reduced tumour suppressor function of p16(INK4A), increases the susceptibility to leukaemic transformation of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A-CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation on ALL risk, highlighting the important and complex roles of CDKN2A-CDKN2B tumour suppressors in leukaemogenesis.Heng Xu, Hui Zhang, Wenjian Yang, Rachita Yadav, Alanna C. Morrison, Maoxiang Qian, Meenakshi Devidas, Yu Liu, Virginia Perez-Andreu, Xujie Zhao, Julie M. Gastier-Foster, Philip J. Lupo, Geoff Neale, Elizabeth Raetz, Eric Larsen, W. Paul Bowman, William L. Carroll, Naomi Winick, Richard Williams, Torben Hansen, Jens-Christian Holm, Elaine Mardis, Robert Fulton, Ching-Hon Pui, Jinghui Zhang, Charles G. Mullighan, William E. Evans, Stephen P. Hunger, Ramneek Gupta, Kjeld Schmiegelow, Mignon L. Loh, Mary V. Relling, Jun J. Yan

A Standard Protocol for Liana Censuses

A recent increase in published studies of lianas has been paralleled by a proliferation of protocols for censusing lianas. This article seeks to increase uniformity in liana inventories by providing specific recommendations for the determination of which taxa to include, the location of diameter measurement points on individual stems, the setting of minimum stem diameter cutoffs, the treatment of multiple‐stemmed and rooted clonal groups, and the measurement of noncylindrical stems. Use of more uniform liana censusing protocols may facilitate comparison of independently collected data sets and further our understanding of global patterns in liana abundance, diversity, biomass, and dynamics

Intense Transpositional Activity of Insertion Sequences in an Ancient Obligate Endosymbiont

The streamlined genomes of ancient obligate endosymbionts generally lack transposable elements, such as insertion sequences (IS). Yet, the genome of Wolbachia, one of the most abundant bacterial endosymbionts on Earth, is littered with IS. Such a paradox raises the question as to why there are so many ISs in the genome of this ancient endosymbiont. To address this question, we investigated IS transpositional activity in the unculturable Wolbachia by tracking the evolutionary dynamics and history of ISWpi1 elements. We show that 1) ISWpi1 is widespread in Wolbachia, being present in at least 55% of the 40 sampled strains, 2) ISWpi1 copies exhibit virtually identical nucleotide sequences both within and among Wolbachia genomes and possess an intact transposase gene, 3) individual ISWpi1 copies are differentially inserted among Wolbachia genomes, and 4) ISWpi1 occurs at variable copy numbers among Wolbachia genomes. Collectively, our results provide compelling evidence for intense ISWpi1 transpositional activity and frequent ISWpi1 horizontal transmission among strains during recent Wolbachia evolution. Thus, the genomes of ancient obligate endosymbionts can carry high loads of functional and transpositionally active transposable elements. Our results also indicate that Wolbachia genomes have experienced multiple and temporally distinct ISWpi1 invasions during their evolutionary history. Such recurrent exposition to new IS invasions may explain, at least partly, the unusually high density of transposable elements found in the genomes of Wolbachia endosymbionts

Building galaxies by accretion and in-situ star formation

We examine galaxy formation in a cosmological AMR simulation, which includes two high resolution boxes, one centered on a 3 \times 10^14 M\odot cluster, and one centered on a void. We examine the evolution of 611 massive (M\ast > 10^10M\odot) galaxies. We find that the fraction of the final stellar mass which is accreted from other galaxies is between 15 and 40% and increases with stellar mass. The accreted fraction does not depend strongly on environment at a given stellar mass, but the galaxies in groups and cluster environments are older and underwent mergers earlier than galaxies in lower density environments. On average, the accreted stars are ~2.5 Gyrs older, and ~0.15 dex more metal poor than the stars formed in-situ. Accreted stellar material typically lies on the outskirts of galaxies; the average half-light radius of the accreted stars is 2.6 times larger than that of the in-situ stars. This leads to radial gradients in age and metallicity for massive galaxies, in qualitative agreement with observations. Massive galaxies grow by mergers at a rate of approximately 2.6% per Gyr. These mergers have a median (mass-weighted) mass ratio less than 0.26 \pm 0.21, with an absolute lower limit of 0.20, for galaxies with M\ast ~ 10^12 M\odot. This suggests that major mergers do not dominate in the accretion history of massive galaxies. All of these results agree qualitatively with results from SPH simulations by Oser et al. (2010, 2012).Comment: 18 pages, 12 figures, submitted to MNRA

Approaching the Problem of Time with a Combined Semiclassical-Records-Histories Scheme

I approach the Problem of Time and other foundations of Quantum Cosmology using a combined histories, timeless and semiclassical approach. This approach is along the lines pursued by Halliwell. It involves the timeless probabilities for dynamical trajectories entering regions of configuration space, which are computed within the semiclassical regime. Moreover, the objects that Halliwell uses in this approach commute with the Hamiltonian constraint, H. This approach has not hitherto been considered for models that also possess nontrivial linear constraints, Lin. This paper carries this out for some concrete relational particle models (RPM's). If there is also commutation with Lin - the Kuchar observables condition - the constructed objects are Dirac observables. Moreover, this paper shows that the problem of Kuchar observables is explicitly resolved for 1- and 2-d RPM's. Then as a first route to Halliwell's approach for nontrivial linear constraints that is also a construction of Dirac observables, I consider theories for which Kuchar observables are formally known, giving the relational triangle as an example. As a second route, I apply an indirect method that generalizes both group-averaging and Barbour's best matching. For conceptual clarity, my study involves the simpler case of Halliwell 2003 sharp-edged window function. I leave the elsewise-improved softened case of Halliwell 2009 for a subsequent Paper II. Finally, I provide comments on Halliwell's approach and how well it fares as regards the various facets of the Problem of Time and as an implementation of QM propositions.Comment: An improved version of the text, and with various further references. 25 pages, 4 figure

N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells

© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. R-loops are nucleic acid structures formed by an RNA:DNA hybrid and unpaired single-stranded DNA that represent a source of genomic instability in mammalian cells1–4. Here we show that N6-methyladenosine (m6A) modification, contributing to different aspects of messenger RNA metabolism5,6, is detectable on the majority of RNA:DNA hybrids in human pluripotent stem cells. We demonstrate that m6A-containing R-loops accumulate during G2/M and are depleted at G0/G1 phases of the cell cycle, and that the m6A reader promoting mRNA degradation, YTHDF2 (ref. 7), interacts with R-loop-enriched loci in dividing cells. Consequently, YTHDF2 knockout leads to increased R-loop levels, cell growth retardation and accumulation of γH2AX, a marker for DNA double-strand breaks, in mammalian cells. Our results suggest that m6A regulates accumulation of R-loops, implying a role for this modification in safeguarding genomic stability

Multiplicity Structure of the Hadronic Final State in Diffractive Deep-Inelastic Scattering at HERA

The multiplicity structure of the hadronic system X produced in deep-inelastic processes at HERA of the type ep -> eXY, where Y is a hadronic system with mass M_Y< 1.6 GeV and where the squared momentum transfer at the pY vertex, t, is limited to |t|<1 GeV^2, is studied as a function of the invariant mass M_X of the system X. Results are presented on multiplicity distributions and multiplicity moments, rapidity spectra and forward-backward correlations in the centre-of-mass system of X. The data are compared to results in e+e- annihilation, fixed-target lepton-nucleon collisions, hadro-produced diffractive final states and to non-diffractive hadron-hadron collisions. The comparison suggests a production mechanism of virtual photon dissociation which involves a mixture of partonic states and a significant gluon content. The data are well described by a model, based on a QCD-Regge analysis of the diffractive structure function, which assumes a large hard gluonic component of the colourless exchange at low Q^2. A model with soft colour interactions is also successful.Comment: 22 pages, 4 figures, submitted to Eur. Phys. J., error in first submission - omitted bibliograph