bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation
Authors: Lee Abby C. , Chakladar Jaideep , Li Wei Tse , Chen Chengyu , Chang Eric Y. , Wang-Rodriguez Jessica , Ongkeko Weg M. 
Published: July 2020

AbstractCOVID-19, caused by the virus SARS-CoV-2, has infected millions worldwide. This pandemic overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping, with over 1 billion smokers and vapers worldwide. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined 3 independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cig led to upregulations of pro-inflammatory cytokine production and expression of genes related to inflammasomes. Vaping flavor-less and nicotine-less e-cig, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping, specifically use of flavored or nicotine-containing e-cigs, may critically exacerbate COVID-19-related inflammation or increase susceptibility to the disease. Further scientific and public health investigations should be undertaken to address these concerning links between COVID-19 and e-cig/smoking.
A multifunctional type IA DNA/RNA topoisomerase with RNA hydrolysis and rRNA processing activities fromMycobacterium smegmatisandMycobacterium tuberculosis
Authors: Rani Phoolwanti , Kalladi Shashwath Malli , Bansia Harsh , Rao Sandhya , Jha Rajiv Kumar , Jain Paras , Bhaduri Tisha , Nagaraja Valakunja 
Published: July 2020

AbstractTopoisomerases maintain topological homeostasis of bacterial chromosomes by catalysing changes in DNA linking number. The resolution of RNA entanglements occurring in the cell would also require catalytic action of topoisomerases. We describe RNA topoisomerase and hydrolysis activities in DNA topoisomerase I (topo I) from mycobacteria. The interaction of topo I with mRNA, tRNA and rRNA suggested its role in some aspect of RNA metabolism; the enzyme participates in rRNA maturation via its RNA hydrolysis activity. Accumulation of rRNA precursors in a topo I knockdown strain and the rescue of rRNA processing deficiency in RNaseE knockdown cells by topo I expression, indicated the enzyme’s back-up support to RNases involved in rRNA processing. We demonstrate that the active site tyrosine of the enzyme mediates catalytic reactions with both DNA/RNA substrates, and RNA topoisomerase activity can follow two reaction paths in contrast to its DNA topoisomerase activity. Mutation in the canonical proton relay pathway impacts DNA topoisomerase activity while retaining activity on RNA substrates. The mycobacterial topo I thus exemplifies the resourcefulness and parsimony of biological catalysis in harnessing the limited chemical repertoire at its disposal to find common solutions to mechanistically-related challenges of phosphodiester breakage/exchange reactions in DNA and RNA that are essential for cell survival.
tRNA-modifying enzyme mutations induce codon-specific mistranslation and protein aggregation in yeast
Authors: Tavares Joana F , Davis Nick K. , Poim Ana , Reis Andreia , Kellner Stefanie , Sousa Inês , Soares Ana R. , Moura Gabriela M R , Dedon Peter C , Santos Manuel A S 
Published: July 2020

Abstract/SummaryProtein synthesis rate and accuracy are essential forbona fideprotein synthesis and proteome homeostasis (proteostasis), however the mRNA translation elongation factors that prevent protein mistranslation, misfolding and aggregation are poorly understood. To address this question, we evaluated the role of 70 yeast tRNA modifying enzyme genes on protein aggregation and used mass spectrometry to identify the aggregated and mistranslated proteins. We show that the mitochondrial tRNA-modifying enzyme Slm3 thiolates the cytoplasmic tRNAs at position 34 and that decreased levels of mcm5s2U34inSLM3mutants are compensated by increasing mcm5U34, ncm5U34and ncm5Um34levels. In the tRNA gene knockout strains, stress response proteins are overrepresented in protein aggregates and their genes are enriched in codons decoded by tRNAs lacking mcm5U34, mcm5s2U34, ncm5U34, ncm5Um34, modifications. Increased rates of amino acid misincorporation were detected in the yeastELP1, SLM3andTRM9gene knockout mutants at protein sites that specifically mapped to the codons sites that are decoded by the hypomodified tRNAs, demonstrating that U34tRNA modifications safeguard the proteome from translational errors, misfolding and cellular proteotoxic stress.
Single-cell analysis reveals the function of lung progenitor cells in COVID-19 patients
Authors: Zhao Zixian , Zhao Yu , Zhou Yueqing , Wang Xiaofan , Zhang Ting , Zuo Wei 
Published: July 2020

AbstractThe high mortality of severe 2019 novel coronavirus disease (COVID-19) cases is mainly caused by acute respiratory distress syndrome (ARDS), which is characterized by increased permeability of the alveolar epithelial barriers, pulmonary edema and consequently inflammatory tissue damage. Some but not all patients showed full functional recovery after the devastating lung damage, and so far there is little knowledge about the lung repair process1. Here by analyzing the bronchoalveolar lavage fluid (BALF) of COVID-19 patients through single cell RNA-sequencing (scRNA-Seq), we found that in severe (or critical) cases, there is remarkable expansion of TM4SF1+ and KRT5+ lung progenitor cells. The two distinct populations of progenitor cells could play crucial roles in alveolar cell regeneration and epithelial barrier re-establishment, respectively. In order to understand the function of KRT5+ progenitors in vivo, we transplanted a single KRT5+ cell-derived cell population into damaged mouse lung. Time-course single-cell transcriptomic analysis showed that the transplanted KRT5+ progenitors could long-term engrafted into host lung and differentiate into HOPX+ OCLN+ alveolar barrier cell which restored the epithelial barrier and efficiently prevented inflammatory cell infiltration. Similar barrier cells were also identified in some COVID-19 patients with massive leukocyte infiltration. Altogether this work uncovered the mechanism that how various lung progenitor cells work in concert to prevent and replenish alveoli loss post severe SARS-CoV-2 infection.
Complex plant metabolomes guide fitness-relevant foraging decisions of a specialist herbivore
Authors: Machado Ricardo A. R. , Theepan Vanitha , Robert Christelle A.M. , Züst Tobias , Hu Lingfei , Su Qi , Schimmel Bernardus C. J. , Erb Matthias 
Published: July 2020

AbstractPlants produce complex mixtures of primary and secondary metabolites. Herbivores use these metabolites as behavioral cues to increase their fitness. However, how herbivores integrate different metabolite classes into fitness-relevant foraging decisionsin plantais poorly understood. We developed a molecular manipulative approach to modulate the availability of sugars and benzoxazinoid secondary metabolites as foraging cues for a specialist maize herbivore, the western corn rootworm. By disrupting sugar perception in the western corn rootworm and benzoxazinoid production in maize, we show that sugars and benzoxazinoids act as distinct and dynamically integrated mediators of short-distance host finding and acceptance. While sugars improve the capacity of rootworm larvae to find a host plant and to distinguish post-embryonic from less nutritious embryonic roots, benzoxazinoids are specifically required for the latter. Host acceptance in the form of root damage is increased by benzoxazinoids and sugars in an additive manner. This pattern is driven by increasing damage to post-embryonic roots in the presence of benzoxazinoids and sugars. Benzoxazinoid- and sugar-mediated foraging directly improves western corn rootworm growth and survival. Interestingly, western corn rootworm larvae retain a substantial fraction of their capacity to feed and survive on maize plants even when both classes of chemical cues are almost completely absent. This study unravels fine-grained differentiation and integration of primary and secondary metabolites into herbivore foraging and documents how the capacity to compensate for the lack of important chemical cues enables a specialist herbivore to survive within unpredictable metabolic landscapes.
Cigarette Smoke and Nicotine-Containing E-cigarette Vapor Downregulate Lung WWOX Expression Which is Associated with Increased Severity of Murine ARDS
Authors: Zeng Zhenguo , Chen Weiguo , Moshensky Alexander , Khan Raheel , Crotty-Alexander Laura , Ware Lorraine B. , Aldaz C. Marcelo , Jacobson Jeffrey R. , Dudek Steven M. , Natarajan Viswanathan , Machado Roberto F. , Singla Sunit 
Published: July 2020

AbstractRATIONALEA history of chronic cigarette smoking is known to increase risk for ARDS, but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures, and thus an interesting candidate gene for the study of exposure-related lung disease.METHODS AND RESULTSLungs harvested from current versus former/never smokers exhibited a 47% decrease in WWOX mRNA levels. Exposure to nicotine-containing e-cigarette vapor resulted in an average 57% decrease in WWOX mRNA levels relative to vehicle treated controls. In separate studies, endothelial (EC)-specific WWOX KO versus wild type mice were examined under ARDS-producing conditions. EC WWOX KO mice exhibited significantly greater levels of vascular leak and histologic lung injury. ECs were isolated from digested lungs of untreated EC WWOX KO mice using sorting by flow cytometry for CD31+CD45- cells. These were grown in culture, confirmed to be WWOX-deficient by RT-PCR and Western blotting, and analyzed by electric cell impedance sensing (ECIS) as well as a FITC dextran transwell assay for their barrier properties during MRSA or LPS exposure. WWOX KO ECs demonstrated significantly greater declines in barrier function relative to wild type cells during either MRSA or LPS treatment as measured by both ECIS and the transwell assay.CONCLUSIONThe increased risk for ARDS observed in chronic smokers may be mechanistically linked, at least in part, to lung WWOX downregulation, and this phenomenon may also manifest in the near future in chronic users of e-cigarettes.
A gene-level methylome-wide association analysis identifies novel Alzheimer’s disease genes
Authors: Wu Chong , Bradley Jonathan , Li Yanming , Wu Lang , Deng Hong-Wen 
Published: July 2020

AbstractMotivationTranscriptome-wide association studies (TWAS) have successfully facilitated the discovery of novel genetic risk loci for many complex traits, including late-onset Alzheimer’s disease (AD). However, most existing TWAS methods rely only on gene expression and ignore epigenetic modification (i.e., DNA methylation) and functional regulatory information (i.e., enhancer-promoter interactions), both of which contribute significantly to the genetic basis of AD.ResultsThis motivates us to develop a novel gene-level association testing method that integrates genetically regulated DNA methylation and enhancer-target gene pairs with genome-wide association study (GWAS) summary results. Through simulations, we show that our approach, referred to as the CMO (cross methylome omnibus) test, yielded well controlled type I error rates and achieved much higher statistical power than competing methods under a wide range of scenarios. Furthermore, compared with TWAS, CMO identified an average of 124% more associations when analyzing several brain imaging-related GWAS results. By analyzing to date the largest AD GWAS of 71,880 cases and 383,378 controls, CMO identified six novel loci for AD, which have been ignored by competing methods.Availability and implementationSoftware:https://github.com/ChongWuLab/CMOContactcwu3@fsu.eduSupplementary informationSupplementary data are available at Bioinformatics online.
Longitudinal symptom dynamics of COVID-19 infection in primary care
Authors: Mizrahi Barak , Shilo Smadar , Rossman Hagai , Kalkstein Nir , Marcus Karni , Barer Yael , Keshet Ayya , Shamir-Stein Na’ama , Shalev Varda , Zohar Anat Ekka , Chodick Gabriel , Segal Eran 
Published: July 2020

AbstractObjectiveData regarding the clinical characteristics of COVID-19 infection is rapidly accumulating. However, most studies thus far are based on hospitalized patients and lack longitudinal follow up. As the majority of COVID-19 cases are not hospitalized, prospective studies of symptoms in the population presenting to primary care are needed. Here, we assess the longitudinal dynamic of clinical symptoms in non-hospitalized individuals prior to and throughout the diagnosis of SARS-CoV-2 infection.DesignData on symptoms were extracted from electronic health records (EHR) consisting of both results of PCR tests and symptoms recorded by primary care physicians, and linked longitudinal self reported symptoms.SettingThe second largest Health Maintenance Organization in Israel, Maccabi Health ServicesParticipantsFrom 1/3/2020 to 07/06/2020, information on symptoms from either surveys or primary care visits was available for 206,377 individuals, including 2,471 who tested positive for COVID-19.Main OutcomesLongitudinal prevalence of clinical symptoms in COVID-19 infection diagnosed by PCR testing for SARS-CoV-2 from nasopharyngeal swabs.ResultsIn adults, the most prevalent symptoms recorded in EHR were cough (11.6%), fever (10.3%), and myalgia (7.7%) and the most prevalent self-reported symptoms were cough (21%), fatigue (19%) and rhinorrhea and/or nasal congestion (17%). In children, the most prevalent symptoms recorded in the EHR were fever (7%), cough (5.5%) and abdominal pain (2.4%). Emotional disturbances were documented in 15.9% of the positive adults and 4.2% of the children. Loss of taste and smell, either self-reported or documented by a physician, 3 weeks prior to testing, were the most discriminative symptoms in adults (OR =11.18 and OR=5.47 respectively). Additional symptoms included self reported headache (OR = 2.03) and fatigue (OR = 1.73) and a documentation of syncope, rhinorrhea (OR = 2.09 for both) and fever (OR= 1.62) by a physician. Mean time to recovery was 23.5 ± 9.9 days. Children had a significantly shorter disease duration (21.7 ± 8.8 days, p-value=0.01). Several symptoms, including fatigue, myalgia, runny nose and shortness of breath were reported weeks after recovery.ConclusionsAs the COVID-19 pandemic progresses rapidly worldwide, obtaining accurate information on symptoms and their progression is of essence. Our study shed light on the full clinical spectrum of symptoms experienced by infected individuals in primary care, and may alert physicians for the possibility of COVID-19 infection.
Who is wearing a mask? Gender-, age-, and location-related differences during the COVID-19 pandemic
Authors: Haischer Michael H. , Beilfuss Rachel , Hart Meggie Rose , Opielinski Lauren , Wrucke David , Zirgaitis Gretchen , Uhrich Toni D. , Hunter Sandra K. 
Published: July 2020

AbstractMasks are an effective tool in combatting the spread of COVID-19, but some people still resist wearing them and mask-wearing behavior has not been experimentally studied in the United States. To understand the demographics of mask wearers and resistors, and the impact of mandates on mask-wearing behavior, we observed shoppers (n = 9935) entering retail stores during periods of June, July, and August 2020. Approximately 41% of the June sample wore a mask. At that time, the odds of an individual wearing a mask increased significantly with age and was also 1.5x greater for females than males. Additionally, the odds of observing a mask on an urban or suburban shopper were ~4x that for rural areas. Mask mandates enacted in late July and August increased mask-wearing compliance to over 90% in all groups, but a small percentage of resistors remained. Thus, gender, age, and location factor into whether shoppers in the United States wear a mask or face covering voluntarily. Additionally, mask mandates are necessary to increase mask wearing among the public to a level required to mitigate the spread of COVID-19.
Cross-regulation between RpfG and HtsHs to regulate antibiotic biosynthesis inLysobacter
Authors: Li Kaihuai , Xu Gaoge , Wang Bo , Wu Guichun , Liu Fengquan 
Published: July 2020

AbstractBacterial two-component systems (TCSs) sense and respond to environmental changes and modulate downstream gene expression. However, the mechanism of cross-talk between multiple TCSs is unclear. In this study, we report a previously uncharacterized mechanism by which the TCS protein RpfG interacts with hybrid two-component system (HyTCS) proteins HtsH1, HtsH2 and HtsH3 to regulate antibiotic biosynthesis inLysobacter. RpfG, a phosphodiesterase (PDE), can degrade c-di-GMP to 5’-pGpG and can regulate antibiotic heat-stable antifungal factor (HSAF) biosynthesis in a PDE- independent manner. Thus, we wondered whether RpfG regulate HSAF biosynthesis through interactions with other factors. Subsequently, we demonstrated that RpfG interacts with three HyTCS proteins (HtsH1, HtsH2 and HtsH3), that can inhibit the PDE enzymatic activity of RpfG. Importantly, deletion ofhtsH1,htsH2andhtsH3resulted in significantly decreased HSAF production, and we showed that HtsH1, HtsH2 and HtsH3 depend on their phosphorylation activity to directly regulate HSAF biosynthesis gene expression. Our results reveal that RpfG does not depend on PDE activity to regulate HSAF biosynthesis, rather it interacts with HtsH1, HtsH2 and HtsH3 to do so, a regulatory mechanism that may be a conserved paradigm inLysobacterandXanthomonas.
Enrofloxacin shifts intestinal microbiota and metabolic profiling and hinders recovery fromSalmonella entericasubsp.entericaserovarTyphimuriuminfection in neonatal chickens
Authors: Ma Boheng , Mei Xueran , Lei Changwei , Li Cui , Gao Yufeng , Kong Linghan , Zhai Xiwen , Wang Hongning 
Published: July 2020

ABSTRACTEnrofloxacin is an important antibiotic used for prevention and treatment ofSalmonellainfection in poultry in many countries. However, oral administration of enrofloxacin may lead to the alterations in the microbiota and metabolome in the chicks intestine, thereby reducing colonization resistance to theSalmonellainfection. To study the effects of enrofloxacin on chicken cecalSalmonella, we used different concentrations of enrofloxacin to feed 1-day-old chickens, followed by oral challenge withSalmonella entericasubsp.entericaserovarTyphimurium(S. Typhimurium). We then explored the distribution patterns ofS. Typhimurium in vivoin intestinal contents using quantitative polymerase chain reaction and microbial 16S amplicon sequencing on days 7, 14, and 21. Metabolome sequencing was used to explore the gut metabolome on day 14. Faecalibacterium and Anaerostipes, which are closely related to the chicken intestinal metabolome, were screened using a multi-omics technique. The abundance ofS. Typhimuriumwas significantly higher in the enrofloxacin-treated group than in the untreated group, andS. Typhimuriumpersisted longer. Moreover, the cecal colony structures of the three groups exhibited different characteristics, withLactobacillusreaching its highest abundance on day 21. Notably,S. Typhimuriuminfection is known to affect the fecal metabolome of chickens differently. Thus, our results suggested that enrofloxacin andSalmonellainfections completely altered the intestinal metabolism of chickens.IMPORTANCEIn this study, we examined the effects ofS. Typhimuriuminfection and enrofloxacin treatment on the microbial flora and metabolite synthesis in chicken guts in order to identify target metabolites that may causeS. Typhimuriumcolonization and severe inflammation and to evaluate the important flora that may be associated with these metabolites. Our findings may facilitate the use of antibiotics to preventS. Typhimuriuminfection.
Goodbye Nicky hello Goldie – exploring the opportunities for transitioning tobacco farmers into cannabis production in Malawi
Authors: Sowoya Linda , Akamwaza Chifundo , Matola Austin Mathews , Klein Axel 
Published: July 2020

Purpose
The purpose of this paper is to illustrate the opportunities for tobacco farmers in Malawi from diversifying to cannabis, and the potential benefits for reducing deforestation by producing a cannabis based alternative fuel. It further argues that there are tensions between the conflicting objectives of the Framework Convention on Tobacco Control and the Single Convention on Narcotic Drugs.

Design/methodology/approach
Field interviews were conducted with cannabis farmers, traders and sellers in different parts of Malawi.

Findings
The findings of this study show that there are opportunities for cannabis farmers but they have been blocked by legal impediments. Now that legislative reform have made cannabis cultivation possible, farmers need support in developing products.

Research limitations/implications
Any attempt to provide a precise assessment of the cannabis market in Malawi is constrained by the criminalised status of the product. The suitability of cannabis briquettes as an fuel has yet to be trialled in Malawi.

Social implications
There is an urgent need to revise the drug control conventions to address environmental degradation and deforestation.

Originality/value
The linkage between tobacco farming, deforestation and desertification in Malawi has not been made. This is the first time that hemp has been suggested as an alternative crop for farmers and as a solution to deforestation.
Mythopolitics of “community”: an unstable but necessary category
Authors: Faas A.J. , Marino Elizabeth K. 
Published: July 2020

PurposeThe authors engage a set of critical discussions on key concepts in disaster studies with attention to recent critiques of the concept “community,” which decry the term's imprecision and problematic insinuation of consensus. The authors’ objective is to explore for enduring and redeeming merit in the use of the term in disaster prevention, response and recovery and in collaborative social science research more broadly.Design/methodology/approachThis paper is based on case studies drawn from the authors' ongoing, longitudinal studies of community-based work with Spanish-speaking community leaders in San José, California and rural Indigenous communities in Alaska.FindingsThe authors synthesize unromantic critiques of the community concept that surface important matters of inequality that complicate efforts for decolonizing disaster work with a view of community as an often utopian project servicing redistributions and relocations of the loci of power. It is a term not only invoked in scholarship and the work of governmental and nongovernmental agencies but also one with deeply symbolic and contextualized meaning.Originality/valueThe authors’ interpretation is that we must at once be critical and unromantic in studying and working with “community” while also recognizing its utopian fecundity. Abandoning the concept altogether would not only create a massive lacuna in everyday speech but also we fear too strong a language in opposition to the community concept metaphor telegraphs a hostility toward those who use it to mobilize scarce social, political and material resources to confront power and contest structural violence.