Macrophage transcriptional responses following in vitro infection with a highly virulent African swine fever virus isolate

We used a porcine microarray containing 2,880 cDNAs to investigate the response of macrophages to infection by a virulent African swine fever virus (ASFV) isolate, Malawi LIL20/1. One hundred twenty-five targets were found to be significantly altered at either or both 4 h and 16 h postinfection compared with targets after mock infection. These targets were assigned into three groups according to their temporal expression profiles. Eighty-six targets showed increased expression levels at 4 h postinfection but returned to expression levels similar to those in mock-infected cells at 16 h postinfection. These encoded several proinflammatory cytokines and chemokines, surface proteins, and proteins involved in cell signaling and trafficking pathways. Thirty-four targets showed increased expression levels at 16 h postinfection compared to levels at 4 h postinfection and in mock-infected cells. One host gene showed increased expression levels at both 4 and 16 h postinfection compared to levels in mock-infected cells. The microarray results were validated for 12 selected genes by quantitative real-time PCR. Levels of protein expression and secretion were measured for two proinflammatory cytokines, interleukin 1β and tumor necrosis factor alpha, during a time course of infection with either the virulent Malawi LIL20/1 isolate or the OUR T88/3 nonpathogenic isolate. The results revealed differences between these two ASFV isolates in the amounts of these cytokines secreted from infected cells

Reconciling the climate and ozone response to the 1257 CE Mount Samalas eruption.

The 1257 CE eruption of Mount Samalas (Indonesia) is the source of the largest stratospheric injection of volcanic gases in the Common Era. Sulfur dioxide emissions produced sulfate aerosols that cooled Earth's climate with a range of impacts on society. The coemission of halogenated species has also been speculated to have led to wide-scale ozone depletion. Here we present simulations from HadGEM3-ES, a fully coupled Earth system model, with interactive atmospheric chemistry and a microphysical treatment of sulfate aerosol, used to assess the chemical and climate impacts from the injection of sulfur and halogen species into the stratosphere as a result of the Mt. Samalas eruption. While our model simulations support a surface air temperature response to the eruption of the order of -1°C, performing well against multiple reconstructions of surface temperature from tree-ring records, we find little evidence to support significant injections of halogens into the stratosphere. Including modest fractions of the halogen emissions reported from Mt. Samalas leads to significant impacts on the composition of the atmosphere and on surface temperature. As little as 20% of the halogen inventory from Mt. Samalas reaching the stratosphere would result in catastrophic ozone depletion, extending the surface cooling caused by the eruption. However, based on available proxy records of surface temperature changes, our model results support only very minor fractions (1%) of the halogen inventory reaching the stratosphere and suggest that further constraints are needed to fully resolve the issue.DTP-1502139 NE/S000887/1 NE/N006038/1 ACSIS UKC

Simulating the Climate Response to Atmospheric Oxygen Variability in the Phanerozoic

Abstract. The amount of dioxygen (O2) in the atmosphere may have varied from as little as 10 % to as high as 35 % during the Phanerozoic eon (541 Ma–Present). These changes in the amount of O2 are large enough to have lead to changes in atmospheric mass, which may alter the radiative budget of the atmosphere, leading to this mechanism being invoked to explain discrepancies between climate model simulations and proxy reconstructions of past climates. Here we present the first fully 3D numerical model simulations to investigate the climate impacts of changes in O2 during different climate states using the HadGEM3-AO and HadCM3-BL models. We show that simulations with an increase in O2 content result in increased global mean surface air temperature under conditions of a pre-industrial Holocene climate state, in agreement with idealised 1D and 2D modelling studies. We demonstrate the mechanism behind the warming is complex and involves trade-off between a number of factors. Increasing atmospheric O2 leads to a reduction in incident shortwave radiation at Earth's surface due to Rayleigh scattering, a cooling effect. However, there is a competing warming effect due to an increase in the pressure broadening of greenhouse gas absorption lines and dynamical feedbacks, which alter the meridional heat transport of the ocean, warming polar regions and cooling tropical regions. Case studies from past climates are investigated using HadCM3-BL which show that in the warmest climate states, increasing oxygen may lead to a temperature decrease, as the equilibrium climate sensitivity is lower. For the Maastrichtian (72.1–66.0 Ma), increasing oxygen content leads to a better agreement with proxy reconstructions of surface temperature at that time irrespective of the carbon dioxide content. For the Asselian (298.9–295.0 Ma), increasing oxygen content leads to a warmer global mean surface temperature and reduced carbon storage on land, suggesting that high oxygen content may have been a contributing factor in preventing a Snowball Earth during this period of the early Permian. These climate model simulations reconcile the surface temperature response to oxygen content changes across the hierarchy of model complexity and highlight the broad range of Earth system feedbacks that need to be accounted for when considering the climate response to changes in atmospheric oxygen content. </jats:p

An XTE Archival Search for Coherent X-ray Pulsations in LMXB 4U 1820-30

As part of a large-scale search for coherent pulsations from LMXBs in the RXTE archive, we have completed a detailed series of searches for coherent pulsations of 4U 1820-30 -- an ultracompact LMXB with a binary period of 11.4 min, located in the globular cluster NGC6624. The short binary period implies any coherent signal would be highly accelerated, so we used phase modulation searches, orbital-parameter-fitting coherent searches, and standard acceleration searches to give significant sensitivity to millisecond pulsations. We searched, in four energy bands and at a range of luminosities, a total of 34 archival RXTE observations, 32 of which had on-source integration times longer than 10 ks, and some of which were made consecutively which allowed us to combine them. We found no pulsations. Using our phase modulation search technique, which we ran on all 34 observations, we have been able to place the first stringent (95% confidence) pulsed fraction limits of <~0.8% for all realistic spin frequencies (i.e. <~2kHz) and likely companion masses (0.02Msun <= M_c <= 0.3Msun). Using our orbital-parameter-fitting coherent search, which we ran on only 11 selected observations, we have placed a pulsed fraction limit of <~0.3% for spin frequencies <~1.25kHz and companion masses M_ <= 0.106Msun. By contrast, all five LMXBs known to emit coherent pulsations have intrinsic pulsed fractions in the range 3% to 7% when pulsations are observed. Hence, our searches rule out pulsations with significantly lower pulsed fractions than those already observed.Comment: 10 pages, 5 figures, published in ApJ, the text of this astro-ph version is now identical to the text of the published versio

Deep time diversity of metatherian mammals: Implications for evolutionary history and fossil-record quality

Despite a global fossil record, Metatheria are now largely restricted to Australasia and South America. Most metatherian paleodiversity studies to date are limited to particular subclades, time intervals, and/or regions, and few consider uneven sampling. Here, we present a comprehensive new data set on metatherian fossil occurrences (Barremian to end Pliocene). These data are analyzed using standard rarefaction and shareholder quorum subsampling (including a new protocol for handling Lagerstätte-like localities). Global metatherian diversity was lowest during the Cretaceous, and increased sharply in the Paleocene, when the South American record begins. Global and South American diversity rose in the early Eocene then fell in the late Eocene, in contrast to the North American pattern. In the Oligocene, diversity declined in the Americas, but this was more than offset by Oligocene radiations in Australia. Diversity continued to decrease in Laurasia, with final representatives in North America (excluding the later entry of Didelphis virginiana) and Europe in the early Miocene, and Asia in the middle Miocene. Global metatherian diversity appears to have peaked in the early Miocene, especially in Australia. Following a trough in the late Miocene, the Pliocene saw another increase in global diversity. By this time, metatherian biogeographic distribution had essentially contracted to that of today. Comparison of the raw and sampling-corrected diversity estimates, coupled with evaluation of "coverage" and number of prolific sites, demonstrates that the metatherian fossil record is spatially and temporally extremely patchy. Therefore, assessments of macroevolutionary patterns based on the raw fossil record (as in most previous studies) are inadvisable.Fil: Bennett, C. Verity. University College London; Estados UnidosFil: Upchurch, Paul. University College London; Estados UnidosFil: Goin, Francisco Javier. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goswami, Anjadi. University College London; Estados Unido

A scoping review of medical education research in family medicine

Background: Little is known about the state of education research within family medicine. As family medicine education models develop, it is important to develop an understanding of the current state of this research and develop ways to advance the field. Methods: We conducted a scoping review of family medicine education research to describe 1) research topic areas and 2) the methodologies and methods used to study these topics. MEDLINE, Social Sciences Abstracts and ERIC electronic databases were searched. 817 full text articles from 2002 to 2012 were screened; 624 articles were included in the review. Results: The following research topic areas were identified: continuing education, curriculum development, undergraduate education, teaching methods, assessment techniques, selection of entrants, non-clinical skills, professional and faculty development, clinical decision-making and resident well-being. Quantitative studies comprised the large majority of research approaches; overall minimal methodological details were provided. Conclusions: Our review highlights an overall need for increased sophisticated in methodological approaches to education research in family medicine, a problem that could be ameliorated by multiple strategies including better engagement of methodologists throughout the research process. The results provide guidance for future family medicine education research programs

Implementation of U.K. Earth system models for CMIP6

We describe the scientific and technical implementation of two models for a core set of experiments contributing to the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The models used are the physical atmosphere-land-ocean-sea ice model HadGEM3-GC3.1 and the Earth system model UKESM1 which adds a carbon-nitrogen cycle and atmospheric chemistry to HadGEM3-GC3.1. The model results are constrained by the external boundary conditions (forcing data) and initial conditions.We outline the scientific rationale and assumptions made in specifying these. Notable details of the implementation include an ozone redistribution scheme for prescribed ozone simulations (HadGEM3-GC3.1) to avoid inconsistencies with the model's thermal tropopause, and land use change in dynamic vegetation simulations (UKESM1) whose influence will be subject to potential biases in the simulation of background natural vegetation.We discuss the implications of these decisions for interpretation of the simulation results. These simulations are expensive in terms of human and CPU resources and will underpin many further experiments; we describe some of the technical steps taken to ensure their scientific robustness and reproducibility

The Association Between Depressive Symptoms and Accumulation of Stress Among Black Men in the Health and Retirement Study

Background and Objectives: Among the multiple factors posited to drive the health inequities that black men experience, the fundamental role of stress in the production of poor health is a key component. Allostatic load (AL) is considered to be a byproduct of stressors related to cumulative disadvantage. Exposure to chronic stress is associated with poorer mental health including depressive symptoms. Few studies have investigated how AL contributes to depressive symptoms among black men. The purpose of the cross-sectional study was to examine the association between AL and depressive symptoms among middle- to old age black men. Research Design and Methods: This project used the 2010 and 2012 wave of the Health and Retirement Study enhanced face-to-face interview that included a biomarker assessment and psychosocial questionnaire. Depressive symptoms, assessed by the endorsement of 3 or more symptoms on the Center for Epidemiological Studies—Depression 8-item scale, was the outcome variable. The main independent variable, AL, score was calculated by summing the number values that were in the high range for that particular biomarker value scores ranging from 0 to 7. black men whose AL score was 3 or greater were considered to be in the high AL group. Modified Poisson regression was used to estimate prevalence ratios (PRs) and corresponding 95% confidence intervals (CIs). Results: There was a larger proportion of black men in the high AL group who reported depressive symptoms (30.0% vs.20.0%) compared with black men in the low AL group. After adjusting for age, education, income, drinking, and smoking status, the prevalence of reporting 3 or more depressive symptoms was statistically significant among black men in the high AL group (PR = 1.61 [95% CI: 1.20–2.17]) than black men in the low AL group. Discussion and Implications: Exposure to chronic stress is related to reporting 3 or more depressive symptoms among black men after controlling for potential confounders. Improving the social and economic conditions for which black men work, play, and pray is key to reducing stress, thereby potentially leading to the reporting of fewer depressive symptoms