Serine Phosphorylation of HIV-1 Vpu and Its Binding to Tetherin Regulates Interaction with Clathrin Adaptors

HIV-1 Vpu prevents incorporation of tetherin (BST2/ CD317) into budding virions and targets it for ESCRT-dependent endosomal degradation via a clathrin-dependent process. This requires a variant acidic dileucine-sorting motif (ExxxLV) in Vpu. Structural studies demonstrate that recombinant Vpu/tetherin fusions can form a ternary complex with the clathrin adaptor AP-1. However, open questions still exist about Vpu's mechanism of action. Particularly, whether endosomal degradation and the recruitment of the E3 ubiquitin ligase SCFβTRCP1/2 to a conserved phosphorylated binding site, DSGNES, are required for antagonism. Re-evaluation of the phenotype of Vpu phosphorylation mutants and naturally occurring allelic variants reveals that the requirement for the Vpu phosphoserine motif in tetherin antagonism is dissociable from SCFβTRCP1/2 and ESCRT-dependent tetherin degradation. Vpu phospho-mutants phenocopy ExxxLV mutants, and can be rescued by direct clathrin interaction in the absence of SCFβTRCP1/2 recruitment. Moreover, we demonstrate physical interaction between Vpu and AP-1 or AP-2 in cells. This requires Vpu/tetherin transmembrane domain interactions as well as the ExxxLV motif. Importantly, it also requires the Vpu phosphoserine motif and adjacent acidic residues. Taken together these data explain the discordance between the role of SCFβTRCP1/2 and Vpu phosphorylation in tetherin antagonism, and indicate that phosphorylation of Vpu in Vpu/tetherin complexes regulates promiscuous recruitment of adaptors, implicating clathrin-dependent sorting as an essential first step in tetherin antagonism

The potential impact of COVID-19-related disruption on tuberculosis burden.

Before the coronavirus disease 2019 (COVID-19) pandemic, over 4000 people were dying from tuberculosis (TB) every day. As with past emergencies, the impact of COVID-19 on TB outcomes is a serious cause for concern but is currently unknown. Health system overload, due to high numbers of COVID-19 cases, as well as interventions necessary to limit the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), could result in severe reductions in health service availability and access for the detection and treatment of TB cases. However, physical distancing interventions could also limit Mycobacterium tuberculosis transmission outside of households, where most transmission occurs. This has not been adequately explored in concurrent work, and it is currently unclear whether social distancing could compensate for disruptions in TB services, and what the impact of these combined COVID-19 disruption effects on TB burden is likely to be

The Justice Challenge: Honors Endeavors Innovative Pedagogies through the Grand Challenge Scholars Program

Honors practitioners from fourteen colleges and programs across the country at land-grant, public, and minority-serving institutions partner with agricultural experts to secure a United States Department of Agriculture (USDA) Higher Education Challenge grant focused on the themes of food justice, climate justice, and sustainable agriculture. Authors describe the program’s origin, objectives, and curricular outgrowths, highlighting its efficacy for empowering students in areas of systems thinking, career readiness, leadership in the service of addressing social needs, and learning through civic engagement

ISSUES IN REFORMING TARIFF-RATE IMPORT QUOTAS IN THE AGREEMENT ON AGRICULTURE IN THE WTO

Contents: The Economics of Tariff Rate Quotas and the Effects of Trade Liberalization; TRQs and GATT Rules; An Overview of Tariffs, Quotas and Imports Worldwide; TRQs in the European Union; U.S. TRQs for Sugar, Tobacco and Peanuts; Dairy TRQs in the United States; Tariff Rate Quota Implementation and Administration by Developing Countries; Management of Tariff Rate Quotas in Korea and Japan; Tariff Rate Quota Administration in Canadian Agriculture; The Case of Australia and New Zealand Facing TRQs; The 1999 WTO Panel Report on the EU's Common Market Organization for Bananas; AssessmentInternational Relations/Trade,

Quick phases of infantile nystagmus show the saccadic inhibition effect

Purpose: Infantile nystagmus (IN) is a pathological, involuntary oscillation of the eyes consisting of slow, drifting eye movements interspersed with rapid reorienting quick phases. The extent to which quick phases of IN are programmed similarly to saccadic eye movements remains unknown. We investigated whether IN quick phases exhibit 'saccadic inhibition', a phenomenon typically related to normal targeting saccades, in which the initiation of the eye movement is systematically delayed by task-irrelevant visual distractors. Methods: We recorded eye position from 10 observers with early-onset idiopathic nystagmus while task-irrelevant distractor stimuli were flashed along the top and bottom of a large screen at ±10° eccentricity. The latency distributions of quick phases were measured with respect to these distractor flashes. Two additional participants, one with possible albinism and one with fusion maldevelopment nystagmus syndrome, were also tested. Results: All observers showed that a distractor flash delayed the execution of quick phases that would otherwise have occurred around 100 ms later, exactly as in the standard saccadic inhibition effect. The delay did not appear to differ between the two main nystagmus types under investigation (idiopathic IN with unidirectional and bidirectional jerk). Conclusions: The presence of the saccadic inhibition effect in IN quick phases is consistent with the idea that quick phases and saccades share a common programming pathway. This could allow quick phases to take on flexible, goal-directed behaviour, at odds with the view that IN quick phases are stereotyped, involuntary eye movements

Assessment of corrosive attack of Fe9Cr1Mo alloys in pressurised CO2 for prediction of breakaway oxidation

To provide clarity on the poorly-understood mechanism of breakaway oxidation, corrosion of Fe9Cr1Mo steel in pressurised CO is quantified and modelled. The temperature range 400–640 , relevant to nuclear power plants, is emphasised. Attack is in the form of combined oxide scale growth and internal carburisation of the metal. Carbon activity in the metal at its surface exhibits a strong time dependence consistent with the kinetically-limited transport of carbon due to the slow Boudouard reaction. Breakaway is associated with the approach to saturation of the steel with respect to carbon. Diffusion modelling agrees well with steel carbide precipitation observations

Building capacity for injury prevention: a process evaluation of a replication of the Cardiff Violence Prevention Programme in the Southeastern USA

Objectives Violence is a major public health problem in the USA. In 2016, more than 1.6 million assault-related injuries were treated in US emergency departments (EDs). Unfortunately, information about the magnitude and patterns of violent incidents is often incomplete and underreported to law enforcement (LE). In an effort to identify more complete information on violence for the development of prevention programme, a cross-sectoral Cardiff Violence Prevention Programme (Cardiff Model) partnership was established at a large, urban ED with a level I trauma designation and local metropolitan LE agency in the Atlanta, Georgia metropolitan area. The Cardiff Model is a promising violence prevention approach that promotes combining injury data from hospitals and LE. The objective was to describe the Cardiff Model implementation and collaboration between hospital and LE partners. Methods The Cardiff Model was replicated in the USA. A process evaluation was conducted by reviewing project materials, nurse surveys and interviews and ED–LE records. Results Cardiff Model replication centred around four activities: (1) collaboration between the hospital and LE to form a community safety partnership locally called the US Injury Prevention Partnership; (2) building hospital capacity for data collection; (3) data aggregation and analysis and (4) developing and implementing violence prevention interventions based on the data. Conclusions The Cardiff Model can be implemented in the USA for sustainable violent injury data surveillance and sharing. Key components include building a strong ED–LE partnership, communicating with each other and hospital staff, engaging in capacity building and sustainability planning

Multi-Messenger Astronomy with Extremely Large Telescopes

The field of time-domain astrophysics has entered the era of Multi-messenger Astronomy (MMA). One key science goal for the next decade (and beyond) will be to characterize gravitational wave (GW) and neutrino sources using the next generation of Extremely Large Telescopes (ELTs). These studies will have a broad impact across astrophysics, informing our knowledge of the production and enrichment history of the heaviest chemical elements, constrain the dense matter equation of state, provide independent constraints on cosmology, increase our understanding of particle acceleration in shocks and jets, and study the lives of black holes in the universe. Future GW detectors will greatly improve their sensitivity during the coming decade, as will near-infrared telescopes capable of independently finding kilonovae from neutron star mergers. However, the electromagnetic counterparts to high-frequency (LIGO/Virgo band) GW sources will be distant and faint and thus demand ELT capabilities for characterization. ELTs will be important and necessary contributors to an advanced and complete multi-messenger network.Comment: White paper submitted to the Astro2020 Decadal Surve

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

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