Murine gammaherpesvirus-68 glycoprotein B presents a difficult neutralization target to monoclonal antibodies derived from infected mice

Persistent viruses disseminate from immune hosts. They must therefore resist neutralization by antibody. Murine gammaherpesvirus-68 (MHV-68) represents an accessible model with which to address how resistance to neutralization is achieved and how overcoming it might improve infection control. The MHV-68 glycoprotein B (gB), like that of other herpesviruses, is a virion protein that is essential for infectivity. As such, it presents a potential neutralization target. In order to test whether virus-induced antibodies reduce virion infectivity by binding to gB, monoclonal antibodies (mAbs) were derived from MHV-68-infected mice. gB-specific mAbs were common, but only an IgM specific for the gB N terminus reduced virion infectivity significantly. It inhibited MHV-68 entry into BHK-21 cells at a post-binding step that was linked closely to membrane fusion. Reducing the mAb to IgM monomers compromised neutralization severely, suggesting that a pentameric structure was crucial to its function. Antibody treatment never blocked BHK-21 cell infection completely and blocked the infection of NMuMG epithelial cells hardly at all. Virions saturated with antibody also remained infectious to mice. Thus, the MHV-68 gB presents at best a very difficult target for antibody-mediated neutralization

Antibody Inhibition of a Viral Type 1 Interferon Decoy Receptor Cures a Viral Disease by Restoring Interferon Signaling in the Liver

Type 1 interferons (T1-IFNs) play a major role in antiviral defense, but when or how they protect during infections that spread through the lympho-hematogenous route is not known. Orthopoxviruses, including those that produce smallpox and mousepox, spread lympho-hematogenously. They also encode a decoy receptor for T1-IFN, the T1-IFN binding protein (T1-IFNbp), which is essential for virulence. We demonstrate that during mousepox, T1-IFNs protect the liver locally rather than systemically, and that the T1-IFNbp attaches to uninfected cells surrounding infected foci in the liver and the spleen to impair their ability to receive T1-IFN signaling, thus facilitating virus spread. Remarkably, this process can be reversed and mousepox cured late in infection by treating with antibodies that block the biological function of the T1-IFNbp. Thus, our findings provide insights on how T1-IFNs function and are evaded during a viral infection in vivo, and unveil a novel mechanism for antibody-mediated antiviral therapy

The role of networks to overcome large-scale challenges in tomography: The non-clinical tomography users research network

Our ability to visualize and quantify the internal structures of objects via computed tomography (CT) has fundamentally transformed science. As tomographic tools have become more broadly accessible, researchers across diverse disciplines have embraced the ability to investigate the 3D structure-function relationships of an enormous array of items. Whether studying organismal biology, animal models for human health, iterative manufacturing techniques, experimental medical devices, engineering structures, geological and planetary samples, prehistoric artifacts, or fossilized organisms, computed tomography has led to extensive methodological and basic sciences advances and is now a core element in science, technology, engineering, and mathematics (STEM) research and outreach toolkits. Tomorrow's scientific progress is built upon today's innovations. In our data-rich world, this requires access not only to publications but also to supporting data. Reliance on proprietary technologies, combined with the varied objectives of diverse research groups, has resulted in a fragmented tomography-imaging landscape, one that is functional at the individual lab level yet lacks the standardization needed to support efficient and equitable exchange and reuse of data. Developing standards and pipelines for the creation of new and future data, which can also be applied to existing datasets is a challenge that becomes increasingly difficult as the amount and diversity of legacy data grows. Global networks of CT users have proved an effective approach to addressing this kind of multifaceted challenge across a range of fields. Here we describe ongoing efforts to address barriers to recently proposed FAIR (Findability, Accessibility, Interoperability, Reuse) and open science principles by assembling interested parties from research and education communities, industry, publishers, and data repositories to approach these issues jointly in a focused, efficient, and practical way. By outlining the benefits of networks, generally, and drawing on examples from efforts by the Non-Clinical Tomography Users Research Network (NoCTURN), specifically, we illustrate how standardization of data and metadata for reuse can foster interdisciplinary collaborations and create new opportunities for future-looking, large-scale data initiatives

National Psoriasis Foundation COVID-19 Task Force Guidance for Management of Psoriatic Disease During the Pandemic: Version 1

Objective To provide guidance about management of psoriatic disease during the coronavirus disease 2019 (COVID-19) pandemic. Study design A task force (TF) of 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care was convened. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation (NPF) staff. Clinical questions relevant to the psoriatic disease community were informed by questions received by the NPF. A Delphi process was conducted. Results The TF approved 22 guidance statements. The average of the votes was within the category of agreement for all statements. All guidance statements proposed were recommended, 9 with high consensus and 13 with moderate consensus. Limitations The evidence behind many guidance statements is limited in quality. Conclusion These statements provide guidance for the management of patients with psoriatic disease on topics ranging from how the disease and its treatments impact COVID-19 risk and outcome, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 and what they should do if they develop COVID-19. The guidance is intended to be a living document that will be updated by the TF as data emerge

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

The role of networks to overcome large-scale challenges in tomography : the non-clinical tomography users research network

Our ability to visualize and quantify the internal structures of objects via computed tomography (CT) has fundamentally transformed science. As tomographic tools have become more broadly accessible, researchers across diverse disciplines have embraced the ability to investigate the 3D structure-function relationships of an enormous array of items. Whether studying organismal biology, animal models for human health, iterative manufacturing techniques, experimental medical devices, engineering structures, geological and planetary samples, prehistoric artifacts, or fossilized organisms, computed tomography has led to extensive methodological and basic sciences advances and is now a core element in science, technology, engineering, and mathematics (STEM) research and outreach toolkits. Tomorrow's scientific progress is built upon today's innovations. In our data-rich world, this requires access not only to publications but also to supporting data. Reliance on proprietary technologies, combined with the varied objectives of diverse research groups, has resulted in a fragmented tomography-imaging landscape, one that is functional at the individual lab level yet lacks the standardization needed to support efficient and equitable exchange and reuse of data. Developing standards and pipelines for the creation of new and future data, which can also be applied to existing datasets is a challenge that becomes increasingly difficult as the amount and diversity of legacy data grows. Global networks of CT users have proved an effective approach to addressing this kind of multifaceted challenge across a range of fields. Here we describe ongoing efforts to address barriers to recently proposed FAIR (Findability, Accessibility, Interoperability, Reuse) and open science principles by assembling interested parties from research and education communities, industry, publishers, and data repositories to approach these issues jointly in a focused, efficient, and practical way. By outlining the benefits of networks, generally, and drawing on examples from efforts by the Non-Clinical Tomography Users Research Network (NoCTURN), specifically, we illustrate how standardization of data and metadata for reuse can foster interdisciplinary collaborations and create new opportunities for future-looking, large-scale data initiatives

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries