A novel mechanism of RNase L inhibition: Theiler\u27s virus L* protein prevents 2-5A from binding to RNase L

<div><p>The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L <i>in vivo</i>. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A.</p></div

Integrated Geothermal-CO2 Reservoir Systems: Reducing Carbon Intensity through Sustainable Energy Production and Secure CO2 Storage

AbstractLarge-scale geologic CO2 storage (GCS) can be limited by overpressure, while geothermal energy production is often limited by pressure depletion. We investigate how synergistic integration of these complementary systems may enhance the viability of GCS by relieving overpressure, which reduces pore-space competition, the Area of Review, and the risks of CO2 leakage and induced seismicity, and by producing geothermal energy and water, which can defray parasitic energy and water costs of CO2 capture

Classification of Generalized Symmetries for the Vacuum Einstein Equations

A generalized symmetry of a system of differential equations is an infinitesimal transformation depending locally upon the fields and their derivatives which carries solutions to solutions. We classify all generalized symmetries of the vacuum Einstein equations in four spacetime dimensions. To begin, we analyze symmetries that can be built from the metric, curvature, and covariant derivatives of the curvature to any order; these are called natural symmetries and are globally defined on any spacetime manifold. We next classify first-order generalized symmetries, that is, symmetries that depend on the metric and its first derivatives. Finally, using results from the classification of natural symmetries, we reduce the classification of all higher-order generalized symmetries to the first-order case. In each case we find that the generalized symmetries are infinitesimal generalized diffeomorphisms and constant metric scalings. There are no non-trivial conservation laws associated with these symmetries. A novel feature of our analysis is the use of a fundamental set of spinorial coordinates on the infinite jet space of Ricci-flat metrics, which are derived from Penrose's ``exact set of fields'' for the vacuum equations.Comment: 57 pages, plain Te

Global biogeographic patterns of avian morphological diversity

Understanding the biogeographical patterns, and evolutionary and environmental drivers, underpinning morphological diversity are key for determining its origins and conservation. Using a comprehensive set of continuous morphological traits extracted from museum collections of 8353 bird species, including geometric morphometric beak shape data, we find that avian morphological diversity is unevenly distributed globally, even after controlling for species richness, with exceptionally dense packing of species in hyper-diverse tropical hotspots. At the regional level, these areas also have high morphological variance, with species exhibiting high phenotypic diversity. Evolutionary history likely plays a key role in shaping these patterns, with evolutionarily old species contributing to niche expansion, and young species contributing to niche packing. Taken together, these results imply that the tropics are both ‘cradles’ and ‘museums’ of phenotypic diversity

Methyl, ethyl, and propyl nitrates: global distribution and impacts on reactive nitrogen in remote marine environments

Alkyl nitrates (RONO2) are important components of tropospheric reactive nitrogen that serve as reservoirs for nitrogen oxides (NOx ≡ NO + NO2). Here we implement a new simulation of atmospheric methyl, ethyl, and propyl nitrate chemistry in a global chemical transport model (GEOS‐Chem). We show that the model can reproduce the spatial and seasonal variability seen in a 20‐year ensemble of airborne observations. Methyl nitrate accounts for 17 Gg N globally, with maxima over the tropical Pacific and Southern Ocean. Propyl nitrate is enhanced in continental boundary layers, but its global impact (6 Gg N) is limited by a short lifetime (8 days, versus 26 days for methyl nitrate and 14 days for ethyl nitrate) that inhibits long‐range transport. Ethyl nitrate has the smallest impact of the three species (4 Gg N). We find that methyl nitrate is the dominant form of reactive nitrogen (NOy) in the Southern Ocean marine boundary layer, where its addition to the model corrects a large NOy underestimate in austral winter relative to recent aircraft data. RONO2 serve as a small net NOx source to the marine troposphere, except in the northern mid‐latitudes where the continental outflow is enriched in precursors that promote NOx loss via RONO2 formation. Recent growth in NOx emissions from East Asia has enhanced the role of RONO2 as a source of NOx to the remote free troposphere. This relationship implies projected future NOx emissions growth across the southern hemisphere may further enhance the importance of RONO2 as a NOx reservoir

The influence of a major sporting event upon emergency department attendances; A retrospective cross-national European study

Major sporting events may influence attendance levels at hospital emergency departments (ED). Previous research has focussed on the impact of single games, or wins/losses for specific teams/countries, limiting wider generalisations. Here we explore the impact of the Euro 2016 football championships on ED attendances across four participating nations (England, France, Northern Ireland, Wales), using a single methodology. Match days were found to have no significant impact upon daily ED attendances levels. Focussing upon hourly attendances, ED attendances across all countries in the four hour pre-match period were statistically significantly lower than would be expected (OR 0.97, 95% CI 0.94–0.99) and further reduced during matches (OR 0.94, 95% CI 0.91–0.97). In the 4 hour post-match period there was no significant increase in attendances (OR 1.01, 95% CI 0.99–1.04). However, these impacts were highly variable between individual matches: for example in the 4 hour period following the final, involving France, the number of ED attendances in France increased significantly (OR 1.27, 95% CI 1.13–1.42). Overall our results indicate relatively small impacts of major sporting events upon ED attendances. The heterogeneity observed makes it difficult for health providers to predict how major sporting events may affect ED attendances but supports the future development of compatible systems in different countries to support cross-border public health surveillance

Part I. SARS-CoV-2 triggered \u27PANIC\u27 attack in severe COVID-19

The coronavirus disease 2019 (COVID-19) pandemic has produced a world-wide collapse of social and economic infrastructure, as well as constrained our freedom of movement. This respiratory tract infection is nefarious in how it targets the most distal and highly vulnerable aspect of the human bronchopulmonary tree, specifically, the delicate yet irreplaceable alveoli that are responsible for the loading of oxygen upon red cell hemoglobin for use by all of the body\u27s tissues. In most symptomatic individuals, the disease is a mild immune-mediated syndrome, with limited damage to the lung tissues. About 20% of those affected experience a disease course characterized by a cataclysmic set of immune activation responses that can culminate in the diffuse and irreversible obliteration of the distal alveoli, leading to a virtual collapse of the gas-exchange apparatus. Here, in Part I of a duology on the characterization and potential treatment for COVID-19, we define severe COVID-19 as a consequence of the ability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to trigger what we now designate for the first time as a ‘Prolific Activation of a Network-Immune-Inflammatory Crisis’, or ‘PANIC’ Attack, in the alveolar tree. In Part II we describe an immunotherapeutic hypothesis worthy of the organization of a randomized clinical trial in order to ascertain whether a repurposed, generic, inexpensive, and widely available agent is capable of abolishing ‘PANIC’; thereby preventing or mitigating severe COVID-19, with monumental ramifications for world health, and the global pandemic that continues to threaten it

Digital Signal Processing

Contains research objectives and summary of research on seven research projects.Joint Services Electronics Program (Contract DAAB07-76-C-1400)U. S. Navy - Office of Naval Research (Contract N00014-75-C-0951-NR 049-308)National Science Foundation (Grant ENG71-02319-AO2