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Showing papers by "University of Georgia published in 2021"


Journal ArticleDOI
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

1,129 citations


Journal ArticleDOI
TL;DR: It is shown that a family of causal effect parameters are identified in staggered DiD setups, even if differences in observed characteristics create non-parallel outcome dynamics between groups, and the asymptotic properties of the proposed estimators are established.

862 citations



Journal ArticleDOI
TL;DR: In this article, the authors discuss 10 of the most relevant research and practice topics in the field of industrial and organizational psychology that will likely be strongly influenced by COVID-19, including occupational health and safety, work family issues, telecommuting, virtual teamwork, job insecurity, precarious work, leadership, human resources policy, the aging workforce, and careers.
Abstract: Pandemics have historically shaped the world of work in various ways. With COVID-19 presenting as a global pandemic, there is much speculation about the implications of this crisis for the future of work and for people working in organizations. In this article, we discuss 10 of the most relevant research and practice topics in the field of industrial and organizational psychology that will likely be strongly influenced by COVID-19. For each of these topics, the pandemic crisis is creating new work-related challenges, but it is also presenting various opportunities. The topics discussed herein include occupational health and safety, work–family issues, telecommuting, virtual teamwork, job insecurity, precarious work, leadership, human resources policy, the aging workforce, and careers. This article sets the stage for further discussion of various ways in which I-O psychology research and practice can address the issues that COVID-19 creates for work and organizational processes that are affecting workers now and will shape the future of work and organizations in both the short and long term. This article concludes by inviting I-O psychology researchers and practitioners to address the challenges and opportunities of COVID-19 head-on by proactively adapting the work that we do in support of workers, organizations, and society as a whole.

263 citations



Journal ArticleDOI
TL;DR: The survey formally introduces the IRL problem along with its central challenges which include accurate inference, generalizability, correctness of prior knowledge, and growth in solution complexity with problem size and elaborates how the current methods mitigate these challenges.

226 citations


Journal ArticleDOI
TL;DR: It is found that below-ground traits with widest importance in plant and ecosystem functioning are not those most commonly measured, and advocate that establishing causal hierarchical links among root traits will provide a hypothesis-based framework to identify the most parsimonious sets of traits with strongest influence on the functions, and to link genotypes to plant andcosystem functioning.
Abstract: The effects of plants on the biosphere, atmosphere and geosphere are key determinants of terrestrial ecosystem functioning. However, despite substantial progress made regarding plant belowground components, we are still only beginning to explore the complex relationships between root traits and functions. Drawing on the literature in plant physiology, ecophysiology, ecology, agronomy and soil science, we reviewed 24 aspects of plant and ecosystem functioning and their relationships with a number of root system traits, including aspects of architecture, physiology, morphology, anatomy, chemistry, biomechanics and biotic interactions. Based on this assessment, we critically evaluated the current strengths and gaps in our knowledge, and identify future research challenges in the field of root ecology. Most importantly, we found that belowground traits with the broadest importance in plant and ecosystem functioning are not those most commonly measured. Also, the estimation of trait relative importance for functioning requires us to consider a more comprehensive range of functionally relevant traits from a diverse range of species, across environments and over time series. We also advocate that establishing causal hierarchical links among root traits will provide a hypothesis-based framework to identify the most parsimonious sets of traits with the strongest links on functions, and to link genotypes to plant and ecosystem functioning.

205 citations


Journal ArticleDOI
TL;DR: To facilitate proper disposal of PPE debris by the public, it is recommended development of municipal efforts to improve PPE collection methods that are informed by the described PPE waste pathways.

198 citations


Journal ArticleDOI
06 Aug 2021-Science
TL;DR: In this article, de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population were reported.
Abstract: We report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The number of pan-genes in these diverse genomes exceeds 103,000, with approximately a third found across all genotypes. The results demonstrate that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres revealed additional variation in major cytological landmarks. We show that combining structural variation with single-nucleotide polymorphisms can improve the power of quantitative mapping studies. We also document variation at the level of DNA methylation and demonstrate that unmethylated regions are enriched for cis-regulatory elements that contribute to phenotypic variation.

183 citations


Journal ArticleDOI
Jens H. Kuhn1, Scott Adkins2, Daniela Alioto3, S. V. Alkhovsky4  +231 moreInstitutions (125)
TL;DR: The updated taxonomy of Negarnaviricota is presented, as now accepted by the ICTV, after the phylum was amended and emended in March 2020.
Abstract: In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

168 citations


Journal ArticleDOI
TL;DR: The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPath database as mentioned in this paper.
Abstract: The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As a Bioinformatics Resource Center funded by the National Institutes of Health, with additional support from the Welllcome Trust, VEuPathDB supports >500 organisms comprising invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Designed to empower researchers with access to Omics data and bioinformatic analyses, VEuPathDB projects integrate >1700 pre-analysed datasets (and associated metadata) with advanced search capabilities, visualizations, and analysis tools in a graphic interface. Diverse data types are analysed with standardized workflows including an in-house OrthoMCL algorithm for predicting orthology. Comparisons are easily made across datasets, data types and organisms in this unique data mining platform. A new site-wide search facilitates access for both experienced and novice users. Upgraded infrastructure and workflows support numerous updates to the web interface, tools, searches and strategies, and Galaxy workspace where users can privately analyse their own data. Forthcoming upgrades include cloud-ready application architecture, expanded support for the Galaxy workspace, tools for interrogating host-pathogen interactions, and improved interactions with affiliated databases (ClinEpiDB, MicrobiomeDB) and other scientific resources, and increased interoperability with the Bacterial & Viral BRC.

Journal ArticleDOI
TL;DR: A major aim of this guide is to help break down barriers between the many subdisciplines of root ecology and ecophysiology, broaden researchers’ views on the multiple aspects of root study and create favourable conditions for the inception of comprehensive experiments on the role of roots in plant and ecosystem functioning.
Abstract: In the context of a recent massive increase in research on plant root functions and their impact on the environment, root ecologists currently face many important challenges to keep on generating cutting-edge, meaningful and integrated knowledge. Consideration of the below-ground components in plant and ecosystem studies has been consistently called for in recent decades, but methodology is disparate and sometimes inappropriate. This handbook, based on the collective effort of a large team of experts, will improve trait comparisons across studies and integration of information across databases by providing standardised methods and controlled vocabularies. It is meant to be used not only as starting point by students and scientists who desire working on below-ground ecosystems, but also by experts for consolidating and broadening their views on multiple aspects of root ecology. Beyond the classical compilation of measurement protocols, we have synthesised recommendations from the literature to provide key background knowledge useful for: (1) defining below-ground plant entities and giving keys for their meaningful dissection, classification and naming beyond the classical fine-root vs coarse-root approach; (2) considering the specificity of root research to produce sound laboratory and field data; (3) describing typical, but overlooked steps for studying roots (e.g. root handling, cleaning and storage); and (4) gathering metadata necessary for the interpretation of results and their reuse. Most importantly, all root traits have been introduced with some degree of ecological context that will be a foundation for understanding their ecological meaning, their typical use and uncertainties, and some methodological and conceptual perspectives for future research. Considering all of this, we urge readers not to solely extract protocol recommendations for trait measurements from this work, but to take a moment to read and reflect on the extensive information contained in this broader guide to root ecology, including sections I-VII and the many introductions to each section and root trait description. Finally, it is critical to understand that a major aim of this guide is to help break down barriers between the many subdisciplines of root ecology and ecophysiology, broaden researchers' views on the multiple aspects of root study and create favourable conditions for the inception of comprehensive experiments on the role of roots in plant and ecosystem functioning.


Journal ArticleDOI
TL;DR: In this article, the authors found that 66.7% (20/30) of long COVID subjects and 10% (2/20) of control subjects in their primary study group were positive for EBV reactivation based on positive titers for EA-D or EBV viral capsid antigen (VCA) IgM.
Abstract: Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein–Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p < 0.001, Fisher’s exact test). A similar ratio was observed in a secondary group of 18 subjects 21–90 days after testing positive for COVID-19, indicating reactivation may occur soon after or concurrently with COVID-19 infection. These findings suggest that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of COVID-19 inflammation-induced EBV reactivation.

Journal ArticleDOI
TL;DR: There were nuanced differences between the egalitarian strategies in their relationships with outcomes, with the Alternating Days egalitarian category emerging as the overall strategy that best preserved wives' and husbands' well-being while allowing both to maintain adequate job performance.
Abstract: There are several existing typologies of dual-earner couples focused on how they dually manage work and family; however, these all assume that couples can outsource childcare during normal work hours and that work is largely conducted outside of the home. Early attempts to control COVID-19 altered these assumptions with daycares/schools closing and the heavy shift to remote work. This calls into question whether couples tended to fall back on familiar gendered patterns to manage work and family, or if they adopted new strategies for the unique pandemic situation. We addressed this question using a sample of 274 dual-earner couples with young children. We content coded couples' qualitative responses about their plans for managing childcare and work commitments and used these codes in a latent class analysis to identify subgroups. Seven classes were identified, with 36.6% of the sample using strategies where women did most or all childcare, 18.9% of the sample using strategies that were not clearly gendered or egalitarian, and 44.5% of the sample using unique egalitarian strategies. We also obtained data from 133 of these couples approximately 7 weeks later regarding their well-being and job performance. Results suggested that women in the Remote Wife Does It All class had the lowest well-being and performance. There were nuanced differences between the egalitarian strategies in their relationships with outcomes, with the Alternating Days egalitarian category emerging as the overall strategy that best preserved wives' and husbands' well-being while allowing both to maintain adequate job performance. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Journal ArticleDOI
TL;DR: The authors proposed a standardized archaeal taxonomy that is derived from a 122-concatenated-protein phylogeny that resolves polyphyletic groups and normalizes ranks based on relative evolutionary divergence.
Abstract: The accrual of genomic data from both cultured and uncultured microorganisms provides new opportunities to develop systematic taxonomies based on evolutionary relationships. Previously, we established a bacterial taxonomy through the Genome Taxonomy Database. Here, we propose a standardized archaeal taxonomy that is derived from a 122-concatenated-protein phylogeny that resolves polyphyletic groups and normalizes ranks based on relative evolutionary divergence. The resulting archaeal taxonomy, which forms part of the Genome Taxonomy Database, is stable for a range of phylogenetic variables including marker gene selection, inference methods, corrections for rate heterogeneity and compositional bias, tree rooting scenarios and expansion of the genome database. Rank normalization is shown to robustly correct for substitution rates varying up to 30-fold using simulated datasets. Taxonomic curation follows the rules of the International Code of Nomenclature of Prokaryotes while taking into account proposals to formally recognize the rank of phylum and to use genome sequences as type material. This taxonomy is based on 2,392 archaeal genomes, 93.3% of which required one or more changes to their existing taxonomy, mainly owing to incomplete classification. We identify 16 archaeal phyla and reclassify 3 major monophyletic units from the former Euryarchaeota and one phylum that unites the Thaumarchaeota-Aigarchaeota-Crenarchaeota-Korarchaeota (TACK) superphylum into a single phylum.

Journal ArticleDOI
TL;DR: In this article, the authors investigated how residents' perceived risk, emotional solidarity, and support for tourism were interrelated amid the pandemic and found that perceived risk was negatively associated with emotional solidarity and support of tourism, and emotional solidarity had a positive impact on support for tourists.
Abstract: Due to the spread of COVID-19 and restrictions on international travel, popular destinations around the world have experienced an influx of domestic tourists. Regardless of the economic benefits that tourists could bring, residents have expressed their concerns about the health risks that would accompany tourists. Residents are not risk-proof or risk-tolerant, but the literature to date has overlooked the relevance and importance of residents' perceived risk associated with tourists. Addressing this research gap, this study investigated how residents’ perceived risk, emotional solidarity, and support for tourism were interrelated amid the pandemic. It was found that perceived risk was negatively associated with emotional solidarity and support for tourism, and emotional solidarity had a positive impact on support for tourism. Also, emotional solidarity was a partial mediator between perceived risk and support for tourism. Theoretical and practical implications of the findings are discussed within the closing of the article.

Journal ArticleDOI
27 May 2021-Cell
TL;DR: Using single-cell genomics in six maize organs, this paper determined the cis- and trans-regulatory factors defining diverse cell identities and coordinating chromatin organization by profiling transcription factor (TF) combinatorics, identifying TFs with non-cell-autonomous activity, and uncovering TFs underlying higher-order chromatin interactions.

Journal ArticleDOI
TL;DR: Glycomic and glycoproteomic analysis of hACE2 expressed in HEK293 cells is described and elucidation of the site-specific glycosylation and its terminal orientations on the h ACE2 receptor can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
Abstract: The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies. Understanding the mode of viral attachment, entry and replication has become a key aspect of such interventions. The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion. The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry. Herein, we describe glycomic and glycoproteomic analysis of hACE2 expressed in HEK293 cells. We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site. To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation. We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation. Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry. The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.

Journal ArticleDOI
MalariaGEN, Ambroise D. Ahouidi1, Mozam Ali2, Jacob Almagro-Garcia2  +160 moreInstitutions (52)
24 Feb 2021
TL;DR: A new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries aims to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.
Abstract: MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Journal ArticleDOI
27 Jan 2021-Nature
TL;DR: In this paper, the authors present the assembly and annotation of the large and complex genome of the polyploid bioenergy crop switchgrass (Panicum virgatum) and investigate patterns of climate adaptation.
Abstract: Long-term climate change and periodic environmental extremes threaten food and fuel security1 and global crop productivity2-4. Although molecular and adaptive breeding strategies can buffer the effects of climatic stress and improve crop resilience5, these approaches require sufficient knowledge of the genes that underlie productivity and adaptation6-knowledge that has been limited to a small number of well-studied model systems. Here we present the assembly and annotation of the large and complex genome of the polyploid bioenergy crop switchgrass (Panicum virgatum). Analysis of biomass and survival among 732 resequenced genotypes, which were grown across 10 common gardens that span 1,800 km of latitude, jointly revealed extensive genomic evidence of climate adaptation. Climate-gene-biomass associations were abundant but varied considerably among deeply diverged gene pools. Furthermore, we found that gene flow accelerated climate adaptation during the postglacial colonization of northern habitats through introgression of alleles from a pre-adapted northern gene pool. The polyploid nature of switchgrass also enhanced adaptive potential through the fractionation of gene function, as there was an increased level of heritable genetic diversity on the nondominant subgenome. In addition to investigating patterns of climate adaptation, the genome resources and gene-trait associations developed here provide breeders with the necessary tools to increase switchgrass yield for the sustainable production of bioenergy.

Journal ArticleDOI
TL;DR: A uniquely comprehensive checklist of bee species distributions and >5,800,000 public bee occurrence records are combined to describe global patterns of bee biodiversity, providing a new baseline and best practices for studies on bees and other understudied invertebrates.

Journal ArticleDOI
TL;DR: In this article, the authors assessed longitudinal changes in body weight and lifestyle behaviors in the US adults during the pandemic and showed that the COVID-19 lockdown periods disrupted weight management among many Americans and that associated health effects are likely to persist.
Abstract: Cross-sectional analyses have shown increased obesogenic behaviors and a potential for weight gain during COVID-19 related peak-lockdown (March–May 2020), but longitudinal data are lacking. This study assessed longitudinal changes in body weight and lifestyle behaviors in the US adults during the pandemic. Methods: We used Qualtrics survey to collect self-reported data on body weight, dietary, physical activity, and psychological variables (n = 727) during the peak-lockdown (April/May) and at post-lockdown (September/October). Peak-lockdown weight data were categorized based on the magnitude of weight gained, maintained, or lost, and behavioral differences were examined between categories at two time points. Results: Body weight increased (+0.62 kg; p 5 lbs of body weight during the peak-lockdown, while 18.2% lost weight. Weight-gainers engaged in riskier dietary behaviors such as frequent ultra-processed food intake (p 5 lbs, 33% continued to gain weight after the lockdown eased, while 28% maintain higher body weight. In weight-gainers, takeout meal frequency increased, and high ultra-processed food intake and stress, and low craving control continued to persist after the lockdown eased. Conclusion: We show that the COVID-19 lockdown periods disrupted weight management among many Americans and that associated health effects are likely to persist.

Journal ArticleDOI
TL;DR: The Concise Guide to PHARMACOLOGY 2021/22 as discussed by the authors provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands.
Abstract: The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15537. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Journal ArticleDOI
TL;DR: In this paper, the authors reveal that the receptor-binding domain (RBD) of the spike (S) protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (Sia), with preference for monosialylated gangliosides.
Abstract: Emerging evidence suggests that host glycans influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we reveal that the receptor-binding domain (RBD) of the spike (S) protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (Sia), with preference for monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind to the RBD. The monomeric affinities (Kd = 100–200 μM) of gangliosides for the RBD are similar to another negatively charged glycan ligand of the RBD proposed as a viral co-receptor, heparan sulfate (HS) dp2–dp6 oligosaccharides. RBD binding and infection of SARS-CoV-2 pseudotyped lentivirus to angiotensin-converting enzyme 2 (ACE2)-expressing cells is decreased following depletion of cell surface Sia levels using three approaches: sialyltransferase (ST) inhibition, genetic knockout of Sia biosynthesis, or neuraminidase treatment. These effects on RBD binding and both pseudotyped and authentic SARS-CoV-2 viral entry are recapitulated with pharmacological or genetic disruption of glycolipid biosynthesis. Together, these results suggest that sialylated glycans, specifically glycolipids, facilitate viral entry of SARS-CoV-2. Mass spectrometric profiling of a glycan library reveals that sialylated glycans, especially sialic acid-containing gangliosides, interact with the RBD of the SARS-CoV-2 spike protein and are involved in ACE2-dependent viral infection.

Journal ArticleDOI
TL;DR: Corporate Social Responsibility: Evolution of a Definitional Construct, and subsequent writings addressing the evolution of a definitional construct have been reviewed in this paper, where the authors comment and reflect on their 1999 BAS article.
Abstract: This perspectives article seeks to comment and reflect on my 1999 BAS article titled “Corporate Social Responsibility: Evolution of a Definitional Construct,” and subsequent writings addressing the...

Journal ArticleDOI
TL;DR: By looking at the politics of classification within machine learning systems, this article demonstrates why the automated interpretation of images is an inherently social and political project.
Abstract: By looking at the politics of classification within machine learning systems, this article demonstrates why the automated interpretation of images is an inherently social and political project. We begin by asking what work images do in computer vision systems, and what is meant by the claim that computers can “recognize” an image? Next, we look at the method for introducing images into computer systems and look at how taxonomies order the foundational concepts that will determine how a system interprets the world. Then we turn to the question of labeling: how humans tell computers which words will relate to a given image. What is at stake in the way AI systems use these labels to classify humans, including by race, gender, emotions, ability, sexuality, and personality? Finally, we turn to the purposes that computer vision is meant to serve in our society—the judgments, choices, and consequences of providing computers with these capacities. Methodologically, we call this an archeology of datasets: studying the material layers of training images and labels, cataloguing the principles and values by which taxonomies are constructed, and analyzing how these taxonomies create the parameters of intelligibility for an AI system. By doing this, we can critically engage with the underlying politics and values of a system, and analyze which normative patterns of life are assumed, supported, and reproduced.

Journal ArticleDOI
TL;DR: In this paper, the authors identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection and show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction.
Abstract: Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.

Journal ArticleDOI
TL;DR: In this paper, the authors used RNA-encoded Cas13a for mitigating influenza virus A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mice and hamsters, respectively.
Abstract: Cas13a has been used to target RNA viruses in cell culture, but efficacy has not been demonstrated in animal models. In this study, we used messenger RNA (mRNA)-encoded Cas13a for mitigating influenza virus A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mice and hamsters, respectively. We designed CRISPR RNAs (crRNAs) specific for PB1 and highly conserved regions of PB2 of influenza virus, and against the replicase and nucleocapsid genes of SARS-CoV-2, and selected the crRNAs that reduced viral RNA levels most efficiently in cell culture. We delivered polymer-formulated Cas13a mRNA and the validated guides to the respiratory tract using a nebulizer. In mice, Cas13a degraded influenza RNA in lung tissue efficiently when delivered after infection, whereas in hamsters, Cas13a delivery reduced SARS-CoV-2 replication and reduced symptoms. Our findings suggest that Cas13a-mediated targeting of pathogenic viruses can mitigate respiratory infections.