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Stress response pathways detect and alleviate adverse conditions to safeguard cell and tissue homeostasis, yet their prolonged activation induces apoptosis and disrupts organismal health1-3. How stress responses are turned off at the right time and place remains poorly understood. Here we report a ubiquitin-dependent mechanism that silences the cellular response to mitochondrial protein import stress. Crucial to this process is the silencing factor of the integrated stress response (SIFI), a large E3 ligase complex mutated in ataxia and in early-onset dementia that degrades both unimported mitochondrial precursors and stress response components. By recognizing bifunctional substrate motifs that equally encode protein localization and stability, the SIFI complex turns off a general stress response after a specific stress event has been resolved. Pharmacological stress response silencing sustains cell survival even if stress resolution failed, which underscores the importance of signal termination and provides a roadmap for treating neurodegenerative diseases caused by mitochondrial import defects.

BackgroundContaining coronavirus disease 2019 (COVID-19) has been difficult, due to both the large number of asymptomatic infected individuals and the long duration of infection. Managing these challenges requires understanding of the differences between asymptomatic vs symptomatic patients and those with a longer duration of infectivity.MethodsIndividuals from Los Angeles were tested for COVID-19, and a group positive for COVID-19 chose to have follow-up testing. Associations between symptoms and demographic factors, viral burden measured by cycle threshold (CT) value, and duration of polymerase chain reaction (PCR) positivity were analyzed.ResultsEighteen point eight percent of patients were positive for COVID-19. Asymptomatic COVID-19-positive patients were significantly younger than symptomatic patients (2.6 years; P

Vortex crystals are quasiregular arrays of like-signed vortices in solid-body rotation embedded within a uniform background of weaker vorticity. Vortex crystals are observed at the poles of Jupiter and in laboratory experiments with magnetized electron plasmas in axisymmetric geometries. We show that vortex crystals form from the free evolution of randomly excited two-dimensional turbulence on an idealized polar cap. Once formed, the crystals are long lived and survive until the end of the simulations (300 crystal-rotation periods). We identify a fundamental length scale, Lγ=(U/γ)1/3, characterizing the size of the crystal in terms of the mean-square velocity U of the fluid and the polar parameter γ=fp/a2p, with fp the Coriolis parameter at the pole and ap the polar radius of the planet.

Lay abstractNaturalistic developmental behavioral interventions for young children with autism spectrum disorder share key elements. However, the extent of similarity between programs within this class of evidence-based interventions is unknown. There is also currently no tool that can be used to measure the implementation of their common elements. This article presents a multi-stage process which began with defining all intervention elements of naturalistic developmental behavioral interventions. Next, intervention experts identified the common elements of naturalistic developmental behavioral interventions using a survey. An observational rating scheme of those common elements, the eight-item NDBI-Fi, was developed. We evaluated the quality of the NDBI-Fi using videos from completed trials of caregiver-implemented naturalistic developmental behavioral interventions. Results showed that the NDBI-Fi measure has promise; it was sensitive to change, related to other similar measures, and demonstrated adequate agreement between raters. This unique measure has the potential to advance intervention science in autism spectrum disorder by providing a tool to measure the implementation of common elements across naturalistic developmental behavioral intervention models. Given that naturalistic developmental behavioral interventions have numerous shared strategies, this may ease clinicians' uncertainty about choosing the "right" intervention package. It also suggests that there may not be a need for extensive training in more than one naturalistic developmental behavioral intervention. Future research should determine whether these common elements are part of other treatment approaches to better understand the quality of services children and families receive as part of usual care.

BackgroundWhile brief intervention (BI) for risky alcohol use generally yields positive effects among those identified by screening, effect sizes are small and there is unexplained heterogeneity in outcome. The heterogeneity may be related to differences in intervention style and content, including elements of motivational interviewing (MI). To date, it has been difficult to interpret the role of MI in BI and these gaps in knowledge interfere with efforts to train, disseminate and implement BI that retains and maximizes efficacy. This study sought to develop BI protocols with varying doses of MI and test their differentiability. Differentiable BI protocols could allow for future studies that prospectively evaluate the role MI plays in affecting BI outcome.MethodsWe developed three intervention protocols: brief advice, standard BI (NIAAA Clinician's Guide), and MI-enhanced BI and administered them to 45 primary care patients who reported exceeding recommended drinking limits. We then rated the BI sessions for fidelity to the assigned protocol as well as MI consistency based on Motivational Interviewing Treatment Integrity (MITI) scale scores. The differentiability of BI protocols was determined by calculating fidelity to assigned protocols and comparing MITI scores using pairwise, Tukey-adjusted comparisons of least squares mean scores.ResultsHigh rates of fidelity to each protocol were achieved. The three BI protocols were also highly differentiable based on MITI scores.ConclusionsThe three interventions can be used in future trials to prospectively examine the role MI has in determining BI outcome. Trial registration clinicaltrials.gov NCT02978027, retrospectively registered 11/28/16.

Models show that to avert dangerous levels of climate change, global carbon dioxide emissions must fall to zero later this century. Most of these emissions arise from energy use. Davis et al. review what it would take to achieve decarbonization of the energy system. Some parts of the energy system are particularly difficult to decarbonize, including aviation, long-distance transport, steel and cement production, and provision of a reliable electricity supply. Current technologies and pathways show promise, but integration of now-discrete energy sectors and industrial processes is vital to achieve minimal emissions. Net emissions of CO2 by human activities - including not only energy services and industrial production but also land use and agriculture - must approach zero in order to stabilize global mean temperature. Energy services such as light-duty transportation, heating, cooling, and lighting may be relatively straightforward to decarbonize by electrifying and generating electricity from variable renewable energy sources (such as wind and solar) and dispatchable ("on-demand") nonrenewable sources (including nuclear energy and fossil fuels with carbon capture and storage). However, other energy services essential to modern civilization entail emissions that are likely to be more difficult to fully eliminate. These difficult-to-decarbonize energy services include aviation, long-distance transport, and shipping; production of carbon-intensive structural materials such as steel and cement; and provision of a reliable electricity supply that meets varying demand. Moreover, demand for such services and products is projected to increase substantially over this century. The long-lived infrastructure built today, for better or worse, will shape the future.Here, we review the special challenges associated with an energy system that does not add any CO2 to the atmosphere (a net-zero emissions energy system). We discuss prominent technological opportunities and barriers for eliminating and/or managing emissions related to the difficult-to-decarbonize services; pitfalls in which near-term actions may make it more difficult or costly to achieve the net-zero emissions goal; and critical areas for research, development, demonstration, and deployment. It may take decades to research, develop, and deploy these new technologies.DOI Link: https://doi.org/10.1126/science.aas9793

The energetics of thermobaricity- and cabbeling-powered deep convection occurring in oceans with cold freshwater overlying warm salty water are investigated here. These quasi-two-layer profiles are widely observed in wintertime polar oceans. The key diagnostic is the ocean convective available potential energy (OCAPE), a concept introduced in a companion piece to this paper (Part I). For an isolated ocean column, OCAPE arises from thermobaricity and is the maximum potential energy (PE) that can be converted into kinetic energy (KE) under adiabatic vertical parcel rearrangements. This study explores the KE budget of convection using two-dimensional numerical simulations and analytical estimates. The authors find that OCAPE is a principal source for KE. However, the complete conversion of OCAPE to KE is inhibited by diabatic processes. Further, this study finds that diabatic processes produce three other distinct contributions to the KE budget: (i) a sink of KE due to the reduction of stratification by vertical mixing, which raises water column's center of mass and thus acts to convert KE to PE; (ii) a source of KE due to cabbeling-induced shrinking of the water column's volume when water masses with different temperatures are mixed, which lowers the water column's center of mass and thus acts to convert PE into KE; and (iii) a reduced production of KE due to diabatic energy conversion of the KE convertible part of the PE to the KE inconvertible part of the PE. Under some simplifying assumptions, the authors also propose a theory to estimate the maximum depth of convection from an energetic perspective. This study provides a potential basis for improving the convection parameterization in ocean models.

Thermobaric convection (type II convection) and thermobaric cabbeling (type III convection) might substantially contribute to vertical mixing, vertical heat transport, and deep-water formation in the World Ocean. However, the extent of this contribution remains poorly constrained. The concept of ocean convective available potential energy (OCAPE), the thermobaric energy source for type II and type III convection, is introduced to improve the diagnosis and prediction of these convection events. OCAPE is analogous to atmospheric CAPE, which is a key energy source for atmospheric moist convection and has long been used to forecast moist convection. OCAPE is the potential energy (PE) stored in an ocean column arising from thermobaricity, defined as the difference between the PE of the ocean column and its minimum possible PE under adiabatic vertical parcel rearrangements. An ocean column may be stably stratified and still have nonzero OCAPE. The authors present an efficient strategy for computing OCAPE accurately for any given column of seawater. They further derive analytical expressions for OCAPE for approximately two-layer ocean columns that are widely observed in polar oceans. This elucidates the dependence of OCAPE on key physical parameters. Hydrographic profiles from the winter Weddell Sea are shown to contain OCAPE (0.001-0.01 J kg-1), and scaling analysis suggests that OCAPE may be substantially enhanced by wintertime surface buoyancy loss. The release of this OCAPE may substantially contribute to the kinetic energy of deep convection in polar oceans.

Earlier autism diagnosis, the importance of early intervention, and development of specific interventions for young children have contributed to the emergence of similar, empirically supported, autism interventions that represent the merging of applied behavioral and developmental sciences. "Naturalistic Developmental Behavioral Interventions (NDBI)" are implemented in natural settings, involve shared control between child and therapist, utilize natural contingencies, and use a variety of behavioral strategies to teach developmentally appropriate and prerequisite skills. We describe the development of NDBIs, their theoretical bases, empirical support, requisite characteristics, common features, and suggest future research needs. We wish to bring parsimony to a field that includes interventions with different names but common features thus improving understanding and choice-making among families, service providers and referring agencies.

Understanding how to source agricultural raw materials sustainably is challenging in today's globalized food system given the variety of issues to be considered and the multitude of suggested indicators for representing these issues. Furthermore, stakeholders in the global food system both impact these issues and are themselves vulnerable to these issues, an important duality that is often implied but not explicitly described. The attention given to these issues and conceptual frameworks varies greatly--depending largely on the stakeholder perspective--as does the set of indicators developed to measure them. To better structure these complex relationships and assess any gaps, we collate a comprehensive list of sustainability issues and a database of sustainability indicators to represent them. To assure a breadth of inclusion, the issues are pulled from the following three perspectives: major global sustainability assessments, sustainability communications from global food companies, and conceptual frameworks of sustainable livelihoods from academic publications. These terms are integrated across perspectives using a common vocabulary, classified by their relevance to impacts and vulnerabilities, and categorized into groups by economic, environmental, physical, human, social, and political characteristics. These issues are then associated with over 2,000 sustainability indicators gathered from existing sources. A gap analysis is then performed to determine if particular issues and issue groups are over or underrepresented. This process results in 44 "integrated" issues--24 impact issues and 36 vulnerability issues--that are composed of 318 "component" issues. The gap analysis shows that although every integrated issue is mentioned at least 40% of the time across perspectives, no issue is mentioned more than 70% of the time. A few issues infrequently mentioned across perspectives also have relatively few indicators available to fully represent them. Issues in the impact framework generally have fewer gaps than those in the vulnerability framework.