Development of a behavioral measure of physical distancing: The o'sickey distancing test

Introduction: Covid-19 has swept the globe and has disproportionately affected the United States with over 600,000 deaths in just over one year. The Centers for Disease Control recommendations for reducing the spread of Covid-19 have focused on physical distancing (PD), the practice of maintaining a distance greater than 6 feet from individuals not in the same household. When employed, this health behavior has been found to reduce the incidence of Covid-19. A review of the measurement literature evaluating PD indicates that PD has been measured at the community level via GPS, using proxy measures of the behavior, or as a construct. These methods can be useful in some situations;however, PD is an observable health behavior and can be reported as such. This study sought to address the issues in measuring PD by creating a new measure of self-reported PD that was: 1) appropriate for individual level measurement, 2) based on participant's self-report of the behavior of PD, and 3) presented a less ambiguous representation of the self-reported behavior. Method: Fifty college students from the University of New Mexico were sampled at a single time-point to evaluate the convergent and concurrent validity of the O'Sickey Distancing Test (ODT). Analysis Plan: To establish convergent validity, individual violations of PD as measured by the ODT were correlated with the Social Distancing Measure (SDM) and participant steps per day using Spearman's rank correlations and by comparing the correlations between the ODT and the number of participant self-reported steps per day and a measure of social distancing and participant steps per day using Steiger's t-test of correlated correlations within a sample. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Performing the City: Space, Movement, and Memory in O Ben'Groes at Droed Amser

In considering some of the aspects that are brought to the site-specific process, this article explores how theatre renegotiates patterns of intraurban movement, enacting complex approaches to space and memory. The focus is on O Ben'Groes at Droed Amser, a Theatr Genedlaethol Cymru and National Theatre Wales production, created in collaboration with BBC Cymru Wales and BBC Arts in 2020 as part of Theatr Genedlaethol Cymru's new programme in response to the COVID-19 emergency and the challenge of creating original dramatic work during lockdown. By allowing virtual audiences to join author and poet Karen Owen on a bus journey from her home and the street where she grew up to Bangor city centre, the production articulated the experience of the city in terms of individual and collective memory, bringing together issues of performance, representation, history, and heritage to reveal alternative layers to the reality of the urban landscape. Memory, I argue, emerged from this production as a performative construct open to renegotiation through a range of present relationships to landscape. In addition to this, the production also offered an alternative to the privileged figure of the walker, performing a subversion of codified patterns of movement.

Economic policy uncertainty, governance institutions and economic performance in Africa: are there regional differences?

In recent years, the global economy has witnessed several uncertainty-inducing events. However, empirical evidence in Africa on the effects of economic policy uncertainty (EPU) on economic activities remains scanty. Besides, the moderating effect of governance institutions on the uncertainty-economic performance relationship in Africa and the likelihood of regional differences in the response of economic activities to EPU on the continent are yet to be investigated. To address these gaps, we applied system GMM and quantile regressions on a panel of forty-seven African countries from 2010 to 2019. We find that while global EPU and EPUs from China, USA and Canada exert considerable influence on economic performance in Africa, the effects of domestic EPU and EPUs from Europe, UK, Japan, and Russia were negligible, suggesting that African economies are resilient to these sources of uncertainty shocks. We also find that governance institutions in Africa are not significantly moderating the uncertainty-economic performance relationship. However, our results highlighted regional differences in the response of economic activities to uncertainty, such that when compared to East and West Africa, economic performance in Central, North and Southern Africa is generally more resilient to global EPU and EPUs from China, USA, Europe and UK. We highlighted the policy implications of these findings.

The Covid-19 pandemic and the STJ decisions on maternity and preventive detention

The article brings the results of quantitative-qualitative research of the jurisprudence of the Superior Court of Justice on granting house arrest to pregnant women, mothers, or guardians of children under 12 years old before and during the Covid-19 pandemic, with CNJ Recommendation 62/2020 as a landmark. Through grounded theory, we identified a continuity in the denials of conversions based on "extremely exceptional situations ", linked to the practice of drug trafficking, even in the face of the serious global health crisis of Covid-19.

Gain and loss of function CFTR alleles modulate COVID-19 clinical outcome

Background/Objectives: We previously demonstrated that carrying a single pathogenic CFTR allele increases the risk for COVID-19 severity and mortality rate. We now aim to clarify the role of several uncharacterized rare alleles, including complex (cis) alleles, and in trans combinations. Method(s): LASSO logistic regression was used for the association of sets of variants, stratified by MAF, with severity. Immortalized cystic fibrosis bronchial epithelial cell lines and Fischer Rat Thyroid cells were transfected by plasmid carrying specific CFTR mutations. YFP-based assays were used to measure CFTR activity. Result(s): Here we functionally demonstrate that the rare (MAF=0.007) complex G576V/R668C allelemitigates the disease by a gain of function mechanism. Several novel CFTR ultra-rare (MAF <0.001) alleles were proved to have a reduced function;they are associated with disease severity either alone (single or complex alleles) or with another hypomorphic allele in the second chromosome, with a global reduction of CFTR activity between 40 to 72%. Conclusion(s): CFTR is a bidirectional modulator of COVID-19 outcome. At-risk subjects do not have open cystic fibrosis before viral infection and therefore are not easily recognisable in the general population unless a genetic analysis is performed. As the CFTR activity is partially retained, CFTR potentiator drugs could be an option as add-on therapy for at-risk patients.

Role of statins in clinical evolution of octogenarian patients admitted due to COVID-19. / Papel de las estatinas en la evolución clínica de los pacientes octogenarios ingresados por COVID-19.

INTRODUCTION AND OBJECTIVES: coronavirus disease 2019 (COVID-19) causes high mortality in elderly patients. Some studies have shown a benefit of statin treatment in the evolution of this disease. Since there are no similar publications in this population group, the aim of this study is to analyze in-hospital mortality in relation to preadmission treatment with statins in an exclusively elderly population of octogenarian patients. MATERIALS AND METHODS: A single-center retrospective cohort study was performed including a total of 258 patients ≥80 years with hospital admission for confirmed COVID-19 between March 1 and May 31, 2020. They were divided into two groups: taking statins prior to admission (n=129) or not (n=129). RESULTS: In-hospital mortality due to COVID-19 in patients ≥80 years (86.13±4.40) during the first wave was 35.7% (95% CI: 30.1-41.7%). Mortality in patients previously taking statins was 25.6% while in those not taking statins was 45.7%. Female sex (RR 0.62 [0.44-0.89]; p=0.008), diabetes (RR 0.61 [0.41-0.92]; p=0.017) and pre-admission treatment with statins (RR 0.58 95% CI [0.41-0.83]; p=0.003) were associated with lower in-hospital mortality. Severe lung involvement was associated with increased in-hospital mortality (RR 1.45 95% CI [1.04-2.03]; p=0.028). Hypertension, obesity, age, cardiovascular disease and a higher Charlson index did not, however, show influence on in-hospital mortality. CONCLUSIONS: In octogenarian patients treated with statins prior to admission for COVID-19 in the first wave, lower in-hospital mortality was observed.

Does COVID-19 pandemic spur digital business transformation? Evidence from selected MENA countries

PurposeIn the light of high reliance on digital technology to mitigate the consequences of the coronavirus disease 2019 (COVID-19) pandemic and its containment measures, this study investigates the factors influencing firms' decision to adopt digital technologies during COVID-19 in four Middle East and Northern African (MENA) countries, namely, Egypt, Jordan, Morocco and Tunisia.Design/methodology/approachThe study used the International Labour Organization (ILO)/Economic Research Forum (ERF) COVID-19 - MENA Monitor Enterprise Survey (CMMENT), comprising 5,480 firms, surveyed during 2020-2021. The empirical model is estimated using the linear probability model (LPM) to address the problem of unobserved heterogeneity between firms, countries, and time.FindingsThe results revealed that firm characteristics, such as firm size and foreign ownership, encourage digital transformation in the business sector. Moreover, firms that face challenges during the pandemic, comply with the containment measures, and receive government assistance are more likely to adopt digital solutions. Furthermore, the results indicated that firms operating in services sector have a higher likelihood to adopt digital technology. Disaggregating the total sample into several sub-samples, the results are robust across countries and technology types, supporting the initial hypothesis that COVID-19 encourages digital transformation in the MENA region.Originality/valueThe study has numerous contributions. First, to the best of the authors' knowledge, this is the sole study that uses micro data collected during the COVID-19 to examine the factors influencing firms' decision to adopt and invest in digital solutions in the MENA countries. Second, the paper employs the LPM estimator to address the issue of unobserved heterogeneity between firms, countries and time. Finally, the paper offers some practical recommendations for accelerating digital transformation in MENA region.

Auditing during a pandemic - can continuous controls monitoring (CCM) address challenges facing internal audit departments?

PurposeDuring a pandemic, with businesses implementing social distancing protocols and work-from-home strategies, the use of continuous controls monitoring (CCM) may add value to the internal audit function. This study aims to examine the use of CCM technologies and the impact on the internal audit function during a pandemic. Design/methodology/approachThis study adopted a case study approach for this study because it focuses on questions of "how" and "what." Case studies provided an opportunity for an in-depth analysis of the phenomena being investigated. Semi-structured interviews were used to collect data. This study did not use sampling. Instead, multiple case studies were used for data collection. FindingsBased on the findings, this study makes several contributions to the literature, for example, in health-care evidence suggests the pandemic has caused internal audit to focus on risk areas. Other industries, such as retail, have invested in CCM. However, in all cases, education and preparedness (or the lack thereof) appeared to significantly influence uptake of CCM. Organizations that made prior investments in CCM technologies experienced greater acceptance in the face of changing demands. Training in emerging technologies is a key competency in supporting audit operations in changing environments. Research limitations/implicationsAs the study was conducted with a small sample of cases, findings cannot be extrapolated nor generalized beyond the case study organizations. Practical implicationsThis study found that several factors limit adoption, exploitation and further development of CCM technologies, such as lack of top management support, acceptance of CCM technologies and suitable education and training of internal audit staff. Originality/valueThis study addresses the issue of the value that CCM offers organizations and whether it is a silver bullet that the internal audit profession needs, particularly when physical access to organizations may be restricted. The COVID-19 pandemic placed considerable focus on digital access. Better IT systems and more data will allow organizations to better support employees, inform strategic and financial decisions and engage stakeholders. During the recovery phase, leveraging investments in CCM technologies will contribute to internal audits' ability to help clients to manage organizational risk.

Assessing the effectiveness of portable HEPA air cleaners for reducing particulate matter exposure in King County, Washington homeless shelters: Implications for community congregate settings.

Over four thousand portable air cleaners (PACs) with high-efficiency particulate air (HEPA) filters were distributed by Public Health - Seattle & King County to homeless shelters during the COVID-19 pandemic. This study aimed to evaluate the real-world effectiveness of these HEPA PACs in reducing indoor particles and understand the factors that affect their use in homeless shelters. Four rooms across three homeless shelters with varying geographic locations and operating conditions were enrolled in this study. At each shelter, multiple PACs were deployed based on the room volume and PAC's clean air delivery rate rating. The energy consumption of these PACs was measured using energy data loggers at 1-min intervals to allow tracking of their use and fan speed for three two-week sampling rounds, separated by single-week gaps, between February and April 2022. Total optical particle number concentration (OPNC) was measured at 2-min intervals at multiple indoor locations and an outdoor ambient location. The empirical indoor and outdoor total OPNC were compared for each site. Additionally, linear mixed-effects regression models (LMERs) were used to assess the relationship between PAC use time and indoor/outdoor total OPNC ratios (I/OOPNC). Based on the LMER models, a 10 % increase in the hourly, daily, and total time PACs were used significantly reduced I/OOPNC by 0.034 [95 % CI: 0.028, 0.040; p < 0.001], 0.051 [95 % CI: 0.020, 0.078; p < 0.001], and 0.252 [95 % CI: 0.150, 0.328; p < 0.001], respectively, indicating that keeping PACs on resulted in significantly lower I/OOPNC. The survey suggested that keeping PACs on and running was the main challenge when operating them in shelters. These findings suggested that HEPA PACs were an effective short-term strategy to reduce indoor particle levels in community congregate living settings during non-wildfire seasons and the need for formulating practical guidance for using them in such an environment.

Hyaluronan 2016–2021

More than 1100 published papers during 2016–2021 have "hyaluronan” in the title. This Encyclopedia of Cell Biology update focuses on 25 of these publications that we considered having important new directions for research on this fascinating Zen macromolecule that has a simple disaccharide structure and a very complex biology. There are likely several more publications during this time that fit this criteria. As hyaluronan has its own International Society (ISHAS) that meets biannually, the on-line booklets of meetings during this time provide insight into the wide range of ongoing hyaluronan research. © 2023 Elsevier Inc. All rights reserved.

Dialect connectedness and tunneling: evidence from China

PurposeThis study aims to examine the effects of dialect connectedness between the chairman and the chief executive officer (CEO) (DCCC) on the tunneling activities of controlling shareholders.Design/methodology/approachThis study uses abnormal related-party transactions (ARPT) as a proxy for tunneling activities and traces dialects of chairmen and CEOs based on the respective birthplace information. Baseline results are examined using a fixed-effects model. The results remain robust when using the instrumental variable approach, propensity score matching (PSM) technique, changing the measurement of tunneling and Heckman two-step selection model.FindingsThe results show that DCCC reduces tunneling activities. This negative association is more pronounced for non-state-owned enterprises and firms whose chairmen and CEOs work in the respective hometowns. DCCC restrains tunneling activities through mechanisms by establishing an informal supervisory effect on CEOs because the CEOs fear reputational damage and strengthening cooperation between chairmen and CEOs. Further analyses suggest that this negative association is more significant when chairmen and CEOs are non-controlling shareholders, but the association is weakened during the coronavirus disease 2019 (COVID-19) crisis.Originality/valueAs dialect is a carrier of culture, this study's results imply that cultural proximity can replace formal mechanisms to enhance corporate governance.

Differences in infant negative affectivity during the COVID-19 pandemic.

This longitudinal study compared infant temperament rated at 3 months postpartum by 263 United-States-based women who gave birth during the COVID-19 pandemic and 72 who gave birth prior to the pandemic. All women completed questionnaires assessing perinatal mental health, social contact, and infant temperament. Mothers whose infants were born during the pandemic reported higher levels of infant negative affectivity as compared with mothers whose infants were born earlier (F(1, 324) = 18.28, p < .001), but did not differ in their ratings of surgency or effortful control. Maternal prenatal depressive symptoms, prenatal stress, and postpartum stress mediated differences in infant negative affectivity  between pandemic and pre-pandemic groups. Within the pandemic group, decreased postpartum social contact was associated with higher ratings of infant negative affectivity. These findings suggest that the pandemic has affected maternal perceptions of infant temperament, perinatal mental health, and social contact.

Este estudio longitudinal comparó el temperamento del infante evaluado a los tres meses después del parto por 263 mujeres con base en Estados Unidos, las cuales dieron a luz durante la pandemia del COVID-19 y 72 que dieron a luz antes de la pandemia. Todas las mujeres completaron cuestionarios para evaluar la salud mental perinatal, el contacto social y el temperamento del infante. Las madres cuyos infantes nacieron durante la pandemia reportaron más altos niveles de afectividad negativa del infante tal como se les comparó con madres cuyos infantes nacieron antes (F(1,324) = 18.28, p<.001), pero no difirieron en sus puntajes de rapidez y astucia o control esforzado. Los síntomas depresivos maternos mediaron la asociación entre la condición de pandemia y la afectividad negativa del infante. Dentro del grupo de pandemia, la baja en el contacto social posterior al parto fue asociada con más altos puntajes en la afectividad negativa del infante. Estos resultados proponen que la pandemia ha afectado las percepciones mentales de la salud mental y el contacto social del temperamento perinatal del infante.

Cette étude longitudinale a comparé le tempérament du nourrisson évalué à trois mois postpartum par 263 femmes basées aux Etats-Unis d'Amérique ayant donné naissance durant la pandémie du COVD-19 et 72 femmes ayant donné naissance avant la pandémie. Toutes les femmes ont rempli des questionnaires évaluant la santé mentale périnatale, le contact social et le tempérament du nourrisson. Les mères dont les nourrissons étaient nés durant la pandémie ont fait état de niveaux plus élevés d'affectivité négative du bébé comparées aux mères dont les bébés étaient nés avant (F(1 324) = 18,28, p <,001), mais n'ont pas divergé dans leurs évaluations du dynamisme ou du contrôle efficace. Les symptômes dépressifs maternels ont médiatisé le lien entre le statue pandémique et l'affectivité négative du nourrisson. Au sein du groupe pandémique le contact social postpartum décru était lié à des évaluations plus élevées de l'affectivité négative du nourrisson. Ces résultats suggèrent que la pandémie a affecté les perceptions maternelles du tempérament du bébé, la santé mentale périnatale et le contact social.

Achieving sustainability: Determinants of conscious green purchasing behavior during the COVID-19 pandemic.

The COVID-19 pandemic has spread worldwide, resulting in crises in public health and sustainable development. Aimed at understanding the determinants of conscious green purchasing behavior (GPB), this paper developed a comprehensive framework linking the moderating effect of negative environmental affective reactions (NEAR) to COVID-19 based on the S-O-R paradigm. Using randomly selected urban residents from China's Yangtze River Delta and Bohai Rim regions, the empirical study was conducted using 559 valid responses. The results show that media and peers are the major social forces activating altruistic and egoistic motivations, while family influence was not significant. Dual motivations significantly mediated the relationships of unconditional and conditional GPB with media exposure and peer influence. Contrary to expectations, NEAR negatively moderated the formation process of conscious GPB. The findings indicate that the influence of peers on conscious GPB through dual motivations is stronger compared to media. Negative affective reactions to COVID-19 were also found to inhibit the impact of peer influence on altruistic and egoistic motivations, as well as the path of altruistic motivation on unconditional GPB. The results of this study have important theoretical and practical implications for enterprise marketing and environmental campaigns, and narrowing the green attitude-behavior gap.

The Benefits and Costs of Using Social Distancing to Flatten the Curve for COVID-19

We examine the net benefits of social distancing to slow the spread of COVID-19 in USA. Social distancing saves lives but imposes large costs on society due to reduced economic activity. We use epidemiological and economic forecasting to perform a rapid benefit–cost analysis of controlling the COVID-19 outbreak. Assuming that social distancing measures can substantially reduce contacts among individuals, we find net benefits of about $5.2 trillion in our benchmark case. We examine the magnitude of the critical parameters that might imply negative net benefits, including the value of statistical life and the discount rate. A key unknown factor is the speed of economic recovery with and without social distancing measures in place. A series of robustness checks also highlight the key role of the value of mortality risk reductions and discounting in the analysis and point to a need for effective economic stimulus when the outbreak has passed.

IDWeek 2022

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.Copyright © 2023 Clarivate.

Optimized nanoparticle-mediated base editing of cystic fibrosis-causing variants

Background: Next-generation SARS-CoV-2 vaccines demonstrated that nanoparticle messenger ribonucleic acid (mRNA) delivery is effective and safe for in vivo delivery in humans. Current treatments for cystic fibrosis (CF) primarily focus on modulator drug therapies designed to correct malfunctioning CF transmembrane conductance regulator (CFTR) protein, but these modulators are ineffective for the 10% of people with CF with variants that do not allow protein production. Among these is the splice variant 3120 + 1G >A, the most common CF-causing mutation in native Africans. Gene editing would allow production of CFTR protein and enhancement of function using available CFTR modulators. We have demonstrated that electroporation of a modified CRISPR-Cas9 base editor to primary human bronchial epithelial cells carrying 3120 + 1G >A and F508del mutant alleles achieved 75% genome editing of the splice variant, resulting in approximately 40% wild-type (WT) CFTR function [1]. Here,we evaluate the effectiveness of several new nanoparticle formulations at delivering green fluorescent protein (GFP) mRNA to CF bronchial epithelial (CFBE41o-) cells. Using the optimal formulation,we then tested the efficacy correction of the 3120 + 1G >Avariant in a CFTR expression minigene (EMG) integrated into the genome of isogenic CFBE cells using mRNA and plasmid deoxyribonucleic acid (DNA) encoding adenine base editor (ABE) and guide (g)RNA. Method(s): GFP served as a reporter to evaluate transfection efficiency, cell viability, and mean fluorescence intensity (MFI) for three dosages (150, 75, 32.5 ng of mRNA), four polymer-to-mRNA to weight (w/w) ratios (60, 40, 30, 20), and four polymers (R, Y, G, B). 7-AAD served as a live/dead stain to quantify viability, with flow cytometry results analyzed using FlowJo software. CFBE cells stably expressing the 3120 + 1G >A EMG were transfected with the optimized nanoparticle formulation to deliver ABE and gRNA at two dosages (150, 75 ng) of mRNA and DNA. CFTR function in CFBE cellswas measured by short circuit current, forskolin stimulation, and inh-172 inhibition as a measure of editing efficiency. Result(s): Flow cytometry showed that polymer R achieved more than 85% GFP transfection, compared with a maximum of approximately 35% for the other three polymers at the maximum 150-ng dose, with approximately 80% viability normalized to untreated cells. In addition, polymer R achieved GFP MFI more than one order of magnitude as high as other formulations (~30 000 vs 2700 MFI) for the other three polymers at 150-ng dose and 40 w/w ratio. CFBE cells transfected with polymer R nanoparticles containing ABE and guide RNA at 75 ng and 150 ng showed mean CFTR function increase to 10 muA 6 (standard error of the mean [SEM] 1.1 muA) (~10% of WT) and 6.3 muA (SEM 0.9 muA) (~6% of WT), respectively. Greater toxicity at the higher dose could explain the larger increase in CFTR current at the lower dose. DNA-encoded ABE plasmid and gRNA showed a less robust increase in CFTR function (2.9 muA [SEM 0.4 muA] for 75-ng dose;3.0 muA [SEM 0.4 muA] for 150-ng dose), which was probably a result of the nanoparticle formulation being optimized for RNA instead of DNA cargo or the additional intracellular barriers that must be overcome for successful DNA delivery. Conclusion(s): We demonstrated that an optimized nanoparticle formulation containing ABE and gRNA can correct splicing of isogenic cells bearing the 3120 + 1G >A CFTR variant, resulting in recovery of CFTR function. In ongoing work, we are adapting these nanoparticles for RNA- and DNAencoded ABE and gRNA delivery to primary human bronchial epithelial cells.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Institutional Quality and Education Quality in Developing Countries: Effects and Transmission Channels

The main objective of this study is to analyze the effect of institutional quality on education quality in developing countries. The literature review explores the channels through which institutional quality transits to affect education quality. The empirical analyses cover a sample of 82 developing countries. The main results obtained using ordinary least squares and two-stage least squares estimators show that institutional quality has a positive effect on student achievement and school completion, and a negative effect on educational failure. Concerning the role of transmission channels, the results show that a deterioration in institutional quality, characterized in particular by the presence of corruption, political instability, or the deterioration of government effectiveness, reduces the effectiveness of public spending on education and the quality of teaching through unethical behavior of teachers and the recruitment of untrained or less trained persons to carry out teaching tasks.

The SARS-CoV-2 Nsp13 Helicase Required for Coronavirus Replication Interacts with Structured Nucleic Acids in a Strand-Specific Manner and Catalyzes a Novel Protein-RNA Remodeling Activity Implicated in the Proofreading Mechanism of the Replication-Transc

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded, positive-sense RNA virus responsible for COVID-19, requires a set of virally encoded nonstructural proteins that compose a replication-transcription complex (RTC) to replicate its 30 kilobase genome. One such nonstructural protein within the RTC is Nsp13, a highly conserved molecular motor ATPase/helicase. Upon purification of the recombinant SARS-CoV-2 Nsp13 protein expressed using a eukaryotic cell-based system, we biochemically characterized the enzyme by examining its catalytic functions, nucleic acid substrate specificity, and putative protein-nucleic acid remodeling activity. We determined that Nsp13 preferentially interacts with single-stranded (ss) DNA compared to ssRNA during loading to unwind with greater efficiency a partial duplex helicase substrate. The binding affinity of Nsp13 to nucleic acid was confirmed through electrophoretic mobility shift assays (EMSA) by determining that Nsp13 binds to DNA substrates with significantly greater efficiency than RNA. These results demonstrate strand-specific interactions of SARS-CoV-2 Nsp13 that dictate its ability to load and unwind structured nucleic acid substrates. We next determined that Nsp13 catalyzed unwinding of double-stranded (ds) RNA forked duplexes on substrates containing a backbone disruption (neutrally charged polyglycol linker (PGL)) was strongly inhibited when the PGL was positioned in the 5' ssRNA overhang, suggesting an unwinding mechanism in which Nsp13 is strictly sensitive to perturbation of the translocating strand sugar-phosphate backbone integrity. Furthermore, we demonstrated for the first time the ability of the coronavirus Nsp13 helicase to disrupt a high-affinity nucleic acid-protein interaction, i.e., a streptavidin tetramer bound to biotinylated RNA or DNA substrate, in a uni-directional manner and with a preferential displacement of the streptavidin complex from biotinylated ssDNA versus ssRNA. In contrast to the poorly hydrolysable ATP-gamma-S or non-hydrolysable AMP-PNP, ATP supports Nsp13-catalyzed disruption of the nucleic acidprotein complex, suggesting that nucleotide binding by Nsp13 is not sufficient for protein-RNA disruption and the chemical energy of nucleoside triphosphate hydrolysis is required to fuel remodeling of protein bound to RNA or DNA. Our results build upon structural studies of the SARS-CoV-2 RTC in which it was suggested that Nsp13 pushes the RNA polymerase (Nsp12) backward on the template RNA strand. Experimental evidence from our studies demonstrate that Nsp13 helicase efficiently remodels a large high affinity protein-RNA complex in a manner dependent on its intrinsic ATP hydrolysis function. We proposed that this novel biochemical activity of Nsp13 is relevant to its role in SARS-CoV-2 RNA processing functions and replication. It was proposed that Nsp13 facilitates proofreading during coronavirus replication when a mismatched base is inadvertently incorporated into the SARS-CoV-2 genome during replication to reposition the RTC so that the proofreading nuclease complex (Nsp14-Nsp10) can gain access and remove the nascently synthesized nucleotide to ensure polymerase fidelity. Our findings implicate a direct catalytic role of Nsp13 in protein-RNA remodeling during coronavirus genome replication beyond its duplex strand separation or structural stabilization of the RTC, yielding new insight into the proofreading mechanism. This work was supported by the Intramural Training Program, National Institute on Aging (NIA), NIH, and a Special COVID-19 Grant from the Office of the Scientific Director, NIA, NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Spatial variability of trace gases (NO2, O3 and CO) over Indian region during 2020 and 2021 COVID-19 lockdowns.

COVID-19 lockdown has given us an opportunity to investigate the pollutant concentrations in response to the restricted anthropogenic activities. The atmospheric concentration levels of nitrogen dioxide (NO2), carbon monoxide (CO) and ozone (O3) have been analysed for the periods during the first wave of COVID-19 lockdown in 2020 (25th March-31st May 2020) and during the partial lockdowns due to second wave in 2021 (25th March-15th June 2021) across India. The trace gas measurements from Ozone Monitoring Instrument (OMI) and Atmosphere InfraRed Sounder (AIRS) satellites have been used. An overall decrease in the concentration of O3 (5-10%) and NO2 (20-40%) have been observed during the 2020 lockdown when compared with business as usual (BAU) period in 2019, 2018 and 2017. However, the CO concentration increased up to 10-25% especially in the central-west region. O3 and NO2 slightly increased or had no change in 2021 lockdown when compared with the BAU period, but CO showed a mixed variation prominently influenced by the biomass burning/forest fire activities. The changes in trace gas levels during 2020 lockdown have been predominantly due to the reduction in the anthropogenic activities, whereas in 2021, the changes have been mostly due to natural factors like meteorology and long-range transport, as the emission levels have been similar to that of BAU. Later phases of 2021 lockdown saw the dominant effect of rainfall events resulting in washout of pollutants. This study reveals that partial or local lockdowns have very less impact on reducing pollution levels on a regional scale as natural factors like atmospheric long-range transport and meteorology play deciding roles on their concentration levels.

Synthesis, Characterization, and Antibacterial Activity of New Isatin Derivatives.

1H-indol-2,3-dione (isatin) class of biologically active compounds have analgesic, anti-microbial, anti-inflammatory, anti-tubercular, anti-proliferative properties, and is also useful for the treatment of SARS-CoV. Schiff bases containing isatin moiety are known to have broad spectrum of biological activities like anti-viral, anti-tubercular, anti-fungal, and anti-bacterial. In this work, several Schiff base derivatives have been synthesized using two methods (synthetic and microwave) by reacting isatin with o-phenylenediamine. The synthesized compounds were structurally characterized and their in-vivo antimicrobial activity was tested against Gram-negative and Gram-positive bacteria using the inhibition zone method. Several newly synthesized isatin derivatives were found effective as antimicrobial agents and showed good potency (compounds 3c, 3d, 6a, 6b, 6d). Compound 3c displayed higher antimicrobial activity than standard drug (Amoxicillin) against Staphylococcus aureus at higher concentration (16 µg/mL) and against Escherichia coli at lower concentration (1 µg/mL).