For Whom the Bell Tolls: Psychopathological and Neurobiological Correlates of the DNA Methylation Index of Time-To-Death

Psychopathology is a risk factor for accelerated biological aging and early mortality. We examined associations between broad underlying dimensions of psychopathology (reflecting internalizing and externalizing psychiatric symptoms), PTSD, and age-adjusted GrimAge (“GrimAge residuals”), a DNA methylation biomarker of mortality risk relative to age. We also examined neurobiological correlates of GrimAge residuals, including neurocognitive functioning, blood-based biomarkers (of inflammation, neuropathology, metabolic disease), and cortical thickness. Data from two independent trauma-exposed military cohorts (n = 647 [62.9% male, Mage = 52], n = 434 [90% male, Mage = 32]) were evaluated using linear regression models to test associations between GrimAge residuals, psychopathology, and health correlates. Externalizing psychopathology significantly predicted GrimAge residuals in both cohorts (ps \u3c 0.028). PTSD predicted GrimAge residuals in the younger (p = 0.001) but not the older cohort. GrimAge residuals were associated with several neurobiological variables available in the younger cohort, including cognitive disinhibition (padj = 0.021), poorer memory recall (padj = 0.023), cardiometabolic pathology (padj \u3c 0.001), oxidative stress (padj = 0.003), astrocyte damage (padj = 0.021), inflammation (C-reactive protein: padj \u3c 0.001; IL-6: padj \u3c 0.001), and immune functioning (padj \u3c 0.001). A subset of inflammatory and neuropathology analytes were available in the older cohort and showed associations with GrimAge residuals (IL-6: padj \u3c 0.001; TNF-α: padj \u3c 0.001). GrimAge residuals were also associated with reduced cortical thickness in right lateral orbitofrontal cortex (padj = 0.018) and left fusiform gyrus (padj = 0.030), which are related to emotion regulation and facial recognition, respectively. Psychopathology may be a common risk factor for elevated mortality risk. GrimAge could help identify those at risk for adverse health outcomes and allow for early disease identification and treatment

PTSD and Alcohol Use Disorders Predict the Pace of Cellular Aging

Advanced epigenetic age is associated with psychopathology and may help to explain the link between psychopathology and physical health morbidity and mortality. Using a longitudinal sample of 171 trauma-exposed Veterans, we modeled the rate of change in epigenetic age across two time points (averaging 5.58 years apart) using two epigenetic age algorithms (GrimAge and Horvath) and tested associations with posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), and depression. Results showed that PTSD (β = .199) and AUD (β = .186) were associated with a quickened pace of epigenetic aging over time (ps \u3c .021). Results replicate and extend prior work and offer foundational support for identifying interventions that slow the pace of biological aging among those with psychopathology

Learning the rules of the ‘student game’: Transforming the ‘student habitus’ through [im]mobility

In recent years, a growing body of literature has emerged concerning the mobilities of students, specifically relating to the interactions between local and non-local students, which can accentuate unequal access to education; social interactions and learner outcomes. Central to much of this literature is a sense that being mobile in institutional choice is the most appropriate and expected approach to successful university life. Conversely, local students, disadvantaged by their age, history, external commitments and immobility, are thought to be unlikely to share the same ‘student experiences’ as their traditional counterparts, leading to feelings of alienation within the student community. This paper will seek to problematise this binary by examining the experiences of a group of local and non-local students studying at the University of Portsmouth using Bourdieu’s reading of habitus and capital. This is useful as it provides a more critical insight into how students’ [dis]advantaged learner identities are [re]produced through their everyday sociability. Moreover, these findings extend previous discussions of first year transitions by questioning the influence of accommodation upon the formation of identities and the initial experiences of ‘being’, or ‘becoming’ students. This paper also seeks to extend previous theoretical tendencies that privilege identity formation through mobility rather than stasis

Neutrino Beams From Electron Capture at High Gamma

We investigate the potential of a flavor pure high gamma electron capture electron neutrino beam directed towards a large water cherenkov detector with 500 kt fiducial mass. The energy of the neutrinos is reconstructed by the position measurement within the detector and superb energy resolution capabilities could be achieved. We estimate the requirements for such a scenario to be competitive to a neutrino/anti-neutrino running at a neutrino factory with less accurate energy resolution. Although the requirements turn out to be extreme, in principle such a scenario could achieve as good abilities to resolve correlations and degeneracies in the search for sin^2(2 theta_13) and delta_CP as a standard neutrino factory experiment.Comment: 21 pages, 7 figures, revised version, to appear in JHEP, Fig.7 extended, minnor changes, results unchange

Multiple photosynthetic transitions, polyploidy, and lateral gene transfer in the grass subtribe Neurachninae

The Neurachninae is the only grass lineage known to contain C3, C4, and C3–C4 intermediate species, and as such has been suggested as a model system for studies of photosynthetic pathway evolution in the Poaceae; however, a lack of a robust phylogenetic framework has hindered this possibility. In this study, plastid and nuclear markers were used to reconstruct evolutionary relationships among Neurachninae species. In addition, photosynthetic types were determined with carbon isotope ratios, and genome sizes with flow cytometry. A high frequency of autopolyploidy was found in the Neurachninae, including in Neurachne munroi F.Muell. and Paraneurachne muelleri S.T.Blake, which independently evolved C4 photosynthesis. Phylogenetic analyses also showed that following their separate C4 origins, these two taxa exchanged a gene encoding the C4 form of phosphoenolpyruvate carboxylase. The C3–C4 intermediate Neurachne minor S.T.Blake is phylogenetically distinct from the two C4 lineages, indicating that intermediacy in this species evolved separately from transitional stages preceding C4 origins. The Neurachninae shows a substantial capacity to evolve new photosynthetic pathways repeatedly. Enablers of these transitions might include anatomical pre-conditions in the C3 ancestor, and frequent autopolyploidization. Transfer of key C4 genetic elements between independently evolved C4 taxa may have also facilitated a rapid adaptation of photosynthesis in these grasses that had to survive in the harsh climate appearing during the late Pliocene in Australia

Dark resonances for ground state transfer of molecular quantum gases

One possible way to produce ultracold, high-phase-space-density quantum gases of molecules in the rovibronic ground state is given by molecule association from quantum-degenerate atomic gases on a Feshbach resonance and subsequent coherent optical multi-photon transfer into the rovibronic ground state. In ultracold samples of Cs_2 molecules, we observe two-photon dark resonances that connect the intermediate rovibrational level |v=73,J=2> with the rovibrational ground state |v=0,J=0> of the singlet $X^1\Sigma_g^+$ ground state potential. For precise dark resonance spectroscopy we exploit the fact that it is possible to efficiently populate the level |v=73,J=2> by two-photon transfer from the dissociation threshold with the stimulated Raman adiabatic passage (STIRAP) technique. We find that at least one of the two-photon resonances is sufficiently strong to allow future implementation of coherent STIRAP transfer of a molecular quantum gas to the rovibrational ground state |v=0,J=0>.Comment: 7 pages, 4 figure

Sampling molecular conformations and dynamics in a multiuser virtual reality framework

Copyright © 2018 The Authors, some rights reserved. We describe a framework for interactive molecular dynamics in a multiuser virtual reality (VR) environment, combining rigorous cloud-mounted atomistic physics simulations with commodity VR hardware, which we have made accessible to readers (see isci.itch.io/nsb-imd). It allows users to visualize and sample, with atomic-level precision, the structures and dynamics of complex molecular structures “on the fly” and to interact with other users in the same virtual environment. A series of controlled studies, in which participants were tasked with a range of molecular manipulation goals (threading methane through a nanotube, changing helical screw sense, and tying a protein knot), quantitatively demonstrate that users within the interactive VR environment can complete sophisticated molecular modeling tasks more quickly than they can using conventional interfaces, especially for molecular pathways and structural transitions whose conformational choreographies are intrinsically three-dimensional. This framework should accelerate progress in nanoscale molecular engineering areas including conformational mapping, drug development, synthetic biology, and catalyst design. More broadly, our findings highlight the potential of VR in scientific domains where three-dimensional dynamics matter, spanning research and education

SMA CO(J=6-5) and 435 micron interferometric imaging of the nuclear region of Arp 220

We have used the Submillimeter Array (SMA) to make the first interferometric observations (beam size ~1") of the 12CO J=6-5 line and 435 micron (690 GHz) continuum emission toward the central region of the nearby ULIRG Arp 220. These observations resolve the eastern and western nuclei from each other, in both the molecular line and dust continuum emission. At 435 micron, the peak intensity of the western nucleus is stronger than the eastern nucleus, and the difference in peak intensities is less than at longer wavelengths. Fitting a simple model to the dust emission observed between 1.3 mm and 435 micron suggests that dust emissivity power law index in the western nucleus is near unity and steeper in the eastern nucleus, about 2, and that the dust emission is optically thick at the shorter wavelength. Comparison with single dish measurements indicate that the interferometer observations are missing ~60% of the dust emission, most likely from a spatially extended component to which these observations are not sensitive. The 12CO J=6-5 line observations clearly resolve kinematically the two nuclei. The distribution and kinematics of the 12CO J=6-5 line appear to be very similar to lower J CO lies observed at similar resolution. Analysis of multiple 12CO line intensities indicates that the molecular gas in both nuclei have similar excitation conditions, although the western nucleus is warmer and denser. The excitation conditions are similar to those found in other extreme environments, including M82, Mrk 231, and BR 1202-0725. Simultaneous lower resolution observations of the 12CO, 13CO, and C18O J=2-1 lines show that the 13CO and C18O lines have similar intensities, which suggests that both of these lines are optically thick, or possibly that extreme high mass star formation has produced in an overabundance of C18O.Comment: 13 pages (emulateapj), 10 figures, Accepted for publication in Ap

COLD GASS, an IRAM legacy survey of molecular gas in massive galaxies: I. Relations between H2, HI, stellar content and structural properties

We are conducting COLD GASS, a legacy survey for molecular gas in nearby galaxies. Using the IRAM 30m telescope, we measure the CO(1-0) line in a sample of ~350 nearby (D=100-200 Mpc), massive galaxies (log(M*/Msun)>10.0). The sample is selected purely according to stellar mass, and therefore provides an unbiased view of molecular gas in these systems. By combining the IRAM data with SDSS photometry and spectroscopy, GALEX imaging and high-quality Arecibo HI data, we investigate the partition of condensed baryons between stars, atomic gas and molecular gas in 0.1-10L* galaxies. In this paper, we present CO luminosities and molecular hydrogen masses for the first 222 galaxies. The overall CO detection rate is 54%, but our survey also uncovers the existence of sharp thresholds in galaxy structural parameters such as stellar mass surface density and concentration index, below which all galaxies have a measurable cold gas component but above which the detection rate of the CO line drops suddenly. The mean molecular gas fraction MH2/M* of the CO detections is 0.066+/-0.039, and this fraction does not depend on stellar mass, but is a strong function of NUV-r colour. Through stacking, we set a firm upper limit of MH2/M*=0.0016+/-0.0005 for red galaxies with NUV-r>5.0. The average molecular-to-atomic hydrogen ratio in present-day galaxies is 0.3, with significant scatter from one galaxy to the next. The existence of strong detection thresholds in both the HI and CO lines suggests that "quenching" processes have occurred in these systems. Intriguingly, atomic gas strongly dominates in the minority of galaxies with significant cold gas that lie above these thresholds. This suggests that some re-accretion of gas may still be possible following the quenching event.Comment: Accepted for publications in MNRAS. 32 pages, 25 figure

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation.

Chronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described. LT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis. Among patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS. Although these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach