bluuebunny/crossref_metadata_2025_split huggingface dataset:
A non-invasive radar system for automated behavioural tracking: application to sheep
Authors: Dore Alexandre , Pasquaretta Cristian , henry Dominique , Ricard Edmond , Bompard Jean-François , Bonneau Mathieu , Boissy Alain , Hazard Dominique , Aubert Hervé , Lihoreau Mathieu 
Published: December 2020

AbstractAutomated quantification of the behaviour of freely moving animals is increasingly needed in ethology, ecology, genetics and evolution. State-of-the-art approaches often require tags to identify animals, high computational power for data collection and processing, and are sensitive to environmental conditions, which limits their large-scale utilisation. Here we introduce a new automated tracking system based on millimetre-wave radars for real time robust and high precision monitoring of untagged animals. To validate our system, we tracked 64 sheep in a standard indoor behavioural test used for genetic selection. First, we show that the proposed radar application is faster and more accurate than conventional video and infrared tracking systems. Next, we illustrate how new behavioural estimators can be derived from the radar data to assess personality traits in sheep for behavioural phenotyping. Finally, we demonstrate that radars can be used for movement tracking at larger spatial scales, in the field, by adjusting operating frequency and radiated electromagnetic power. Millimetre-wave radars thus hold considerable promises for high-throughput recording of the behaviour of animals with various sizes and locomotor modes, in different types of environments.
An IDH-independent mechanism of DNA hypermethylation upon VHL inactivation in cancer
Authors: Artemov Artem V. , Zhenilo Svetlana , Kaplun Daria , Starshin Alexey , Sokolov Alexey , Mazur Alexander M. , Szpotan Justyna , Gawronski Maciej , Modrzejewska Martyna , Gackowski Daniel , Prokhortchouk Egor B. 
Published: December 2020

Hypermethylation of tumor suppressors and other aberrations of DNA methylation in tumors play a significant role in cancer progression. DNA methylation can be affected by various environmental conditions including hypoxia. The response to hypoxia is mainly achieved through activation of the transcription program associated with HIF1a transcription factor. VHL inactivation by genetic or epigenetic events, which also induces aberrant activation of HIF1a, is the most common driver event for renal cancer. With whole-genome bisulfite sequencing and LC-MS, we demonstrated that VHL inactivation induced global genome hypermethylation in human kidney cancer cells under normoxic conditions. This effect was reverted by exogenous expression of wild-type VHL. We show that global genome hypermethylation in VHL mutants can be explained by transcriptional changes in MDH and L2HGDH genes that cause the accumulation of 2-hydroxyglutarate—a metabolite that inhibits DNA demethylation by Tet enzymes. Unlike the known cases of DNA hypermethylation in cancer, 2-hydroxyglutarate was accumulated in IDH wild type cells.Key pointsInactivation of VHL gene leads to genome hypermethylation in kidney cancer cells. The DNA methylation phenotype can be rescued by endogenous expression of wild-type VHL.DNA hypermethylation can be attributed to the accumulation of a Tet inhibitor 2-hydroxyglutarateThe accumulation of 2-hydroxyglutarate in IDH wild-type cells is explained by gene expression changes in key metabolic enzymes (malate dehydrogenase MDH and 2-hydroxyglutrarate dehydrogenase L2HGDH).
Conundrum of re-positives COVID-19 cases: A Systematic review of Case reports and Case series
Authors: Yadav Arun Kumar , Ghosh Subhadeep , Dubey Sudhir 
Published: December 2020

AbstractIntroductionThere have been case reports and case series published for RT PCR positive COVID - 19 cases that became RT PCR negative but subsequently became RT PCR positive after a symptom free interval following a negative RT PCR test. These cases may include re-positive, reactivated and re-infection cases. Hence, the systematic review to summarize and synthesize evidence from all available case series and case reports published was undertaken.MethodologyThe systematic review of case series and case reports was registered with Prospero with registration number CRD42020210446. PRISMA guidelines were followed for conducting the systematic review. Studies published in English language only were considered for the Systematic Review. Inclusion criteria for studies included case reports and case series which have documented cases of positive RT-PCR after a period of improvement or negative RT PCR. Reviews, opinions and animal studies were excluded. Case reports which described clinical presentation or manifestations of COVID-19 cases were also excluded from the studies. Methodological quality was assessed using modified Murad scale.ResultsA total of 30 case reports/case series were included in the study, wherein a total of 219 cases were included. In re-positive cases, the age range varied from 10 months to 91 years. The pooled proportion using random effects was 12% with 95% CI from 09% to 15%. Among the re-positives, a total of 57 cases (26%) of the cases had co-morbidities. A total of 51 (23.3%) and 17 (7.8%) re-positive cases had been treated with antivirals and corticosteroids respectively. Among the symptomatic cases, the disease severity was lesser as compared to the initial episode of illness. Only a few studies have confirmed the presence of antibodies after the first episode. The few studies that had done contact tracing of re-positives did not find any positive cases among those in contact with re-positives.ConclusionThis systematic review presents the review of all the case reports and case series on recurrence of COVID 19 disease. Although limited evidence has been generated due to paucity of such studies and shortcomings in the study designs of case reports and case-series, nonetheless, the evidence generated can still be used in making clinical decisions and framing policy guidelines
Airborne magnetic nanoparticles: environmental risk factors for the transmission of SARS-CoV-2
Authors: Martinez-Boubeta C. , Simeonidis K. 
Published: December 2020

ABSTRACTObjectivesTo examine the impact of concentrations of ambient fine particulate matter (PM2.5) air pollution on the incidence of COVID-19.MethodsPublicly available data of COVID-19 deaths in March/October 2020 were compared with concentrations of PM2.5 measured in previous years at urban and suburban areas in Thessaloniki. Similar publicly available data of PM2.5 concentrations from Tehran were gathered for comparison. Cross-correlation and Granger causality analysis were performed in order to assess linkage.ResultsOn the one hand, the mean PM2.5 concentrations in Thessaloniki were significantly higher in the winter, however the magnetic fraction of particulate matter in the autumn is twice its annual average, suggesting that traffic-related emissions alone may not explain the entire variability of PM2.5. On the other hand, it is implied that changes in coronavirus-related deaths follow changes in airborne magnetite, with the correlation between the two data sets being maximized at the lag time of one-month. Further insight is provided by the monthly pattern of PM2.5 mass concentrations in Tehran. We find that air pollution Granger causes COVID-19 deaths (p<0.05).ConclusionsA significant association has been found between PM2.5 values and the impact of the COVID-19 pandemic on a bunch of regions. Reported links between pollution levels, climate conditions and other factors affecting vulnerability to COVID-19 may instead reflect inhalation exposure to magnetic nanoparticles. A hypothesis has been set that ubiquitous airborne magnetite pollution, together with certain climatic conditions, may promote a longer permanence of the viral particles in the air, thus favoring transmission.Key messagesWhat is already known about this subject?▸▸Due to their small dimensions, airborne particles are able to penetrate through inhalation into many human organs, from the lungs to the cardiovascular system and the brain, which can threaten our health. Research has shown that air pollution is an important cofactor increasing the risk of mortality from coronaviruses.What are the new findings?▸▸Evidence exists that the magnetic fraction of PM has modulated the transmission of SARS-CoV-2 in Thessaloniki, and potentially in any other region in the world.How might this impact on policy or clinical practice in the foreseeable future?▸▸Policymakers should take care not to overestimate the effect of social distancing interventions and should consider the impact of air pollution in current or future epidemic waves.
What positives can be taken from the COVID-19 pandemic in Australia?
Authors: Cornell S , Nickel B , Cvejic E , Bonner C , McCaffery KJ , Ayre J , Copp T , Batcup C , Isautier JMJ , Dakin T , Dodd RH 
Published: December 2020

AbstractObjectiveTo investigate whether Australians have experienced any positive effects during the COVID-19 pandemic, despite the disruption to society and daily life.MethodsNational online longitudinal survey. As part of a June 2020 survey, participants (n=1370) were asked ‘In your life, have you experienced any positive effects from the COVID-19 pandemic’ (yes/no), with a free-text explanation if yes, and also completed the WHO-Five well-being index. Differences were explored by demographic variables. Free-text responses were thematically coded.Results960 participants (70%) reported experiencing at least one positive effect during the COVID-19 pandemic. Living with others (p=.045) and employment situation (p<.001) at baseline (April), were associated with experiencing positive effects. Individuals working for pay from home were more likely to experience positive effects compared to those who were not working for pay (aOR=0.45, 95%CI: 0.32, 0.63, p<.001), or who were working for pay outside the home (aOR=0.40, 95%CI: 0.28, 0.58, p<.001). Age and education were not associated with positive effects when controlling for employment and household numbers. There was an overall effect of gender (p=.001), where those identifying as female were more likely than males (aOR=1.62, 95%CI: 1.25, 2.09) to report experiencing a positive effect. 54.2% of participants reported a sufficient level of wellbeing, 23.2% low wellbeing and a further 22.6% very low wellbeing. Of those experiencing positives, 945/960 (98%) provided an explanation. The three most common themes were ‘Family time’ (33%), ‘Work flexibility’ (29%), and ‘Calmer life’ (19%).ConclusionA large proportion of surveyed Australians reported positive effects resulting from changes to daily life due to the COVID-19 pandemic in Australia. Enhancing these aspects may build community resilience to cope with future pandemic responses. The needs of people living alone, and of those having to work outside the home or who are unemployed, should be considered by health policy makers and employers in future pandemic preparedness efforts, as these groups were least likely to report positive experiences and may be more vulnerable.
Impaired phosphatidylethanolamine metabolism activates a reversible stress response that detects and resolves mutant mitochondrial precursors
Authors: Sam Pingdewinde N. , Calzada Elizabeth , Acoba Michelle Grace , Zhao Tian , Watanabe Yasunori , Nejatfard Anahita , Trinidad Jonathan C. , Shutt Timothy E. , Neal Sonya E. , Claypool Steven M. 
Published: December 2020

SUMMARYPhosphatidylethanolamine made in mitochondria has long been recognized as an important precursor for phosphatidylcholine production that occurs in the endoplasmic reticulum (ER). Recently, the strict mitochondrial localization of the enzyme that makes PE in the mitochondrion, phosphatidylserine decarboxylase 1 (Psd1), was questioned. Since a dual localization of Psd1 to the ER would have far-reaching implications, we initiated our study to independently re-assess the subcellular distribution of Psd1. Our results support the unavoidable conclusion that the vast majority, if not all, of functional Psd1 resides in the mitochondrion. Through our efforts, we discovered that mutant forms of Psd1 that impair a self-processing step needed for it to become functional are dually localized to the ER when expressed in a PE-limiting environment. We conclude that severely impaired cellular PE metabolism provokes an ER-assisted adaptive response that is capable of identifying and resolving nonfunctional mitochondrial precursors.
DETECTION OF SURFACE FORCES BY A CELL WALL MECHANOSENSOR
Authors: Neeli-Venkata Ramakanth , Celador Ruben , Sanchez Yolanda , Minc Nicolas 
Published: December 2020

ABSTRACTSurface receptors of animal cells, such as integrins, promote mechanosensation by forming local clusters as signaling hubs that transduce tensile forces. Walled cells of plants and fungi also feature surface sensors, with long extracellular domains embedded in their cell wall (CW), thought to detect CW injuries and promote repair. How these sensors probe surface forces remains unknown. By studying the conserved CW sensor Wsc1 in fission yeast, we uncovered the formation of micrometer-sized clusters at sites of local force application onto the CW. These clusters form within minutes of CW compression, in dose-dependence with mechanical stress and dissolve upon stress relaxation. Our data support that Wsc1 senses CW mechanical stress and accumulates to local sites of enhanced stress through its CW-associated extracellular WSC domain, independently of canonical polarity, trafficking and downstream CW regulatory pathways. Wsc1 may represent an autonomous module to detect and transduce local surface forces onto the CW.
Phylogeography of Ryukyu insular cicadas: Extensive vicariance by island isolation vs accidental dispersal by super typhoon
Authors: Osozawa Soichi , Kanai Kenichi , Fukuda Haruo , Wakabayashi John 
Published: December 2020

AbstractCicadas tend to be affected by vicariance reflecting poor mobility of nymphs underground and weak flying ability of adults. However, modern collection records of invasive cicada, combined with records of typhoon tracks, and newly obtained phylogeographic data suggest long distance, relatively instantaneous, dispersal of some vicariantly speciated cicadas. We address the importance of this typhoon dispersal mechanism applied to representative species of east Asian endemic cicadas ofCryptotympana,Mogannia,EuterpnosiaandMeimuna. We combine BEAST-dated phylogenic and haplotype network analyses, modern collection data of non-native cicadas available in reports of the Japanese insect associations, modern typhoon records by Japan Meteorological Agency, and our own Quaternary geological constriction data. In conclusion, although Ryukyu endemic cicadas were vicariantly speciated, endemic cicadas on some islands were accidentally dispersed long distances to another island by typhoons, particularly those associated with super typhoons generated since 1.55 Ma.
The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite
Authors: Zhang Min , Wang Chengqi , Oberstaller Jenna , Thomas Phaedra , Otto Thomas D. , Casandra Debora , Boyapalle Sandhya , Adapa Swamy R. , Xu Shulin , Button-Simons Katrina , Mayho Matthew , Rayner Julian C. , Ferdig Michael T. , Jiang Rays H. Y. , Adams John H. 
Published: December 2020

ABSTRACTBackgroundThe emergence and spread ofPlasmodium falciparumparasites resistant to front-line antimalarial artemisinin-combination therapies (ACT) threatens to erase the considerable gains against the disease of the last decade. We developed a new large-scale phenotypic screening pipeline and used it to carry out the first large-scale forward-genetic phenotype screen inP. falciparumto identify genes that allow parasites to survive febrile temperatures.ResultsScreening identified more than 200P. falciparummutants with differential responses to increased temperature. These mutants were more likely to be sensitive to artemisinin derivatives as well as to heightened oxidative stress. Major processes critical forP. falciparumtolerance to febrile temperatures and artemisinin included highly essential, conserved pathways associated with protein-folding, heat-shock and proteasome-mediated degradation, and unexpectedly, isoprenoid biosynthesis, which originated from the ancestral genome of the parasite’s algal endosymbiont-derived plastid, the apicoplast. Apicoplast-targeted genes in general were up-regulated in response to heat shock, as were otherPlasmodiumgenes with orthologs in plant and algal genomes.ConclusionsPlasmodium falciparumparasites appear to exploit their innate febrile-response mechanisms to mediate resistance to artemisinin. Both responses depend on endosymbiotic cynobacterium-related ancestral genes in the parasite’s genome, suggesting a link to the evolutionary origins ofPlasmodiumparasites in free-living ancestors.
SARS-CoV-2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential
Authors: Vithani Neha , Ward Michael D. , Zimmerman Maxwell I. , Novak Borna , Borowsky Jonathan H. , Singh Sukrit , Bowman Gregory R. 
Published: December 2020

AbstractCoronaviruses have caused multiple epidemics in the past two decades, in addition to the current COVID-19 pandemic that is severely damaging global health and the economy. Coronaviruses employ between twenty and thirty proteins to carry out their viral replication cycle including infection, immune evasion, and replication. Among these, nonstructural protein 16 (Nsp16), a 2’-O-methyltransferase, plays an essential role in immune evasion. Nsp16 achieves this by mimicking its human homolog, CMTr1, which methylates mRNA to enhance translation efficiency and distinguish self from other. Unlike human CMTr1, Nsp16 requires a binding partner, Nsp10, to activate its enzymatic activity. The requirement of this binding partner presents two questions that we investigate in this manuscript. First, how does Nsp10 activate Nsp16? While experimentally-derived structures of the active Nsp16/Nsp10 complex exist, structures of inactive, monomeric Nsp16 have yet to be solved. Therefore, it is unclear how Nsp10 activates Nsp16. Using over one millisecond of molecular dynamics simulations of both Nsp16 and its complex with Nsp10, we investigate how the presence of Nsp10 shifts Nsp16’s conformational ensemble in order to activate it. Second, guided by this activation mechanism and Markov state models (MSMs), we investigate if Nsp16 adopts inactive structures with cryptic pockets that, if targeted with a small molecule, could inhibit Nsp16 by stabilizing its inactive state. After identifying such a pocket in SARS-CoV-2 Nsp16, we show that this cryptic pocket also opens in SARS-CoV-1 and MERS, but not in human CMTr1. Therefore, it may be possible to develop pan-coronavirus antivirals that target this cryptic pocket.Statement of SignificanceCoronaviruses are a major threat to human health. These viruses employ molecular machines, called proteins, to infect host cells and replicate. Characterizing the structure and dynamics of these proteins could provide a basis for designing small molecule antivirals. In this work, we use computer simulations to understand the moving parts of an essential SARS-CoV-2 protein, understand how a binding partner turns it on and off, and identify a novel pocket that antivirals could target to shut this protein off. The pocket is also present in other coronaviruses but not in the related human protein, so it could be a valuable target for pan-coronavirus antivirals.
Effective host-directed therapy for tuberculosis by targeted depletion of myeloid-derived suppressor cells using a diphtheria toxin-based fusion protein
Authors: Parveen Sadiya , Lun Shichun , Urbanowski Michael E. , Cardin Mitchell , Murphy John R. , Bishai William R. 
Published: December 2020

ABSTRACTMyeloid-derived suppressor cells (MDSCs) are present in elevated numbers in TB patients and have been found to be permissive forMycobacterium tuberculosis(Mtb) proliferation. To determine whether depletion of MDSCs may improve host control of TB, we used a novel diphtheria toxin-based fusion protein known as DABIL-4 that targets and depletes IL-4-receptor positive cells. We show that DABIL-4 depletes both PMN-MDSCs and M-MDSC in the mouse TB model, and that it reduces the lung bacillary burden ofMtb. These results indicate that MDSC-depleting therapies targeting the IL4 receptor are beneficial in TB and offer an avenue towards host-directed TB therapy.
Did people really drink bleach to prevent COVID-19? A tale of problematic respondents and a guide for measuring rare events in survey data
Authors: Litman Leib , Rosen Zohn , Rosenzweig Cheskie , Weinberger-Litman Sarah L. , Moss Aaron J. , Robinson Jonathan 
Published: December 2020

AbstractSociety is becoming increasingly dependent on survey research. However, surveys can be impacted by participants who are non-attentive, respond randomly to survey questions, and misrepresent who they are and their true attitudes. The impact that such respondents can have on public health research has rarely been systematically examined. In this study we examine whether Americans began to engage in dangerous cleaning practices to avoid Covid-19 infection. Prior findings reported by the CDC have suggested that people began to engage in highly dangerous cleaning practices during the Covid-19 pandemic, including ingesting household cleansers such as bleach. In a series of studies totaling close to 1400 respondents, we show that 80-90% of reports of household cleanser ingestion are made by problematic respondents. These respondents report impossible claims such as ‘recently having had a fatal heart attack’ and ‘eating concrete for its iron content’ at a similar rate to ingesting household cleaners. Additionally, respondents’ frequent misreading or misinterpreting the intent of questions accounted for the rest of such claims. Once inattentive, mischievous, and careless respondents are taken out of the analytic sample we find no evidence that people ingest cleansers to prevent Covid-19 infection. The relationship between dangerous cleaning practices and health outcomes also becomes non-significant once problematic respondents are taken out of the analytic sample. These results show that reported ingestion of household cleaners and other similar dangerous practices are an artifact of problematic respondent bias. The implications of these findings for public health and medical survey research, as well as best practices for avoiding problematic respondents in surveys are discussed.