bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal protection following natural SARS-CoV-2 infection and early vaccine responses: insights from a cohort of community based dental health care professionals
Authors: Shields Adrian M. , Faustini Sian E. , Kristunas Caroline A. , Cook Alex M. , Backhouse Claire , Dunbar Lynsey , Ebanks Daniel , Emmanuel Beena , Crouch Eddie , Kroeger Annika , Hirschfeld Josefine , Sharma Praveen , Jaffery Razza , Nowak Sylwia , Gee Samantha , Drayson Mark T. , Richter Alex G. , Dietrich Thomas , Chapple Iain C. 
Published: February 2021

AbstractBackgroundThe threshold of protection for anti-SARS-CoV-2 spike glycoprotein antibodies and their longevity are not known. Interpretation of serological results in with respect to international reference material can inform this essential question.Methods1,507 West Midlands dental care professionals were recruited into this study in June 2020. Baseline seroprevalence of antibodies directed against the SARS-CoV-2 spike glycoprotein was determined and the cohort was followed longitudinally for 6 months until January/February 2021 through the second wave of the COVID-19 pandemic in the United Kingdom, and commencement of vaccination.ResultsBaseline seroprevalence was 16.3% in this cohort, compared to estimates in the general population of between 6-7%. Seropositivity was retained in over 70% of participants at 3 and 6-month follow up and conferred a 74% reduced risk of infection. During follow-up, no PCR-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. Post-vaccination, antibody responses were more rapid and of higher magnitude in individuals with who were seropositive at baseline.ConclusionNatural infection leads to a serological response that remains detectable in over 70% of individuals 6 months after initial sampling and 9 months from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech vaccine is associated with an antibody response indicative of immunological memory.FundingThe Association of Clinical Biochemistry and Laboratory Medicine and The Institute for Global Innovation (IGI) of the University of Birmingham.
Symptoms associated with a COVID-19 infection in the general population of Vienna
Authors: Munsch Nicolas , Gruarin Stefanie , Nateqi Jama , Lutz Thomas , Binder Michael , Aberle Judith H. , Martin Alistair , Knapp Bernhard 
Published: February 2021

AbstractBackgroundMost clinical studies report the symptoms experienced by those infected with Coronavirus disease 2019 (COVID-19) via patients already hospitalised. Here we analyse the symptoms experienced by the general population in Vienna.MethodsThe Vienna Social Fund (FSW, Vienna, Austria), the Public Health Services of the City of Vienna (MA15) and the private company Symptoma collaborated to implement Vienna’s official online COVID-19 symptom checker. Users answered 12 yes/no questions about symptoms to assess their risk for COVID-19. They could also specify their age and sex, and whether they had contact with someone who tested positive for COVID-19. Depending on the assessed risk of COVID-19 positivity, a SARS-CoV-2 nucleic acid amplification test (NAAT) was performed. In this publication, we analysed which factors (symptoms, sex or age) are associated with COVID-19 positivity. We also trained a classifier to correctly predict COVID-19 positivity from the collected data.ResultsBetween the 2nd of November 2020 and the 18th of November 2021, 9133 people experiencing COVID-19-like symptoms were assessed as high risk by the chatbot and were subsequently tested by a NAAT. Symptoms significantly associated with a positive COVID-19 test were malaise, fatigue, headache, cough, fever, dysgeusia and hyposmia. Our classifier could successfully predict COVID-19 positivity with an Area Under the Curve (AUC) of 0.74.ConclusionThis study provides reliable COVID-19 symptom statistics based on the general population verified by NAATs.
Isolation and structure of the fibril protein, a major component of the internal ribbon forSpiroplasmaswimming
Authors: Sasajima Yuya , Kato Takayuki , Miyata Tomoko , Kawamoto Akihiro , Namba Keiichi , Miyata Makoto 
Published: February 2021

ABSTRACTSpiroplasma, which are known pathogens and commensals of arthropods and plants, are helical-shaped bacteria that lack a peptidoglycan layer.Spiroplasmaswim by alternating between left- and right-handed helicity. Of note, this system is not related to flagellar motility, which is widespread in bacteria. A helical ribbon running along the inner side of the helical cell should be responsible for cell helicity and comprises the bacterial actin homolog, MreB, and a protein specific toSpiroplasma, fibril. Here, we isolated the ribbon and its major component, fibril filament, for electron microscopy (EM) analysis. Single-particle analysis of the fibril filaments using the negative-staining EM revealed a three-dimensional chain structure composed of rings with a size of 11 nm wide and 6 nm long, connected by a backbone cylinder with an 8.7 nm interval with a twist along the filament axis. This structure was verified through EM tomography of quick-freeze deep-etch replica sample, with a focus on its handedness. The handedness and pitch of the helix for the isolated ribbon and fibril filament agreed with those of the cell in the resting state. Structures corresponding to the alternative state were not identified. These results suggest that the helical cell structure is supported by fibril filaments; however, the helical switch is caused by the force generated by the MreB proteins. The isolation and structural outline of the fibril filaments provide crucial information for an in-depth clarification of the unique swimming mechanism ofSpiroplasma.
Odor Blocking Of Stress
Authors: Lee Eun Jeong , Saraiva Luis R. , Hanchate Naresh K. , Ye Xiaolan , Asher Gregory , Ho Jonathan , Buck Linda B. 
Published: February 2021

ABSTRACTScents have been employed for millennia to allay fear and stress, but whether they do so is poorly understood. In response to fear and stress, hypothalamic corticotropin releasing hormone neurons (CRHNs) induce increases in blood stress hormones. Here, we find that certain structurally and perceptually dissimilar odorants can block mouse stress hormone responses to three potent stressors: physical restraint, predator odor, and male-male social confrontation. Both odorants activate GABAergic inhibitory neurons presynaptic to CRHNs in the hypothalamic ventromedial nucleus (VMH). Stimulation of those neurons inhibits restraint-induced activation of CRHNs and stress hormone increase, mimicking a blocking odorant. Conversely, their silencing prevents odorant blocking of both responses. Notably, we also observed odor blocking of stressor activation in neurons presynaptic to CRHNs in the bed nucleus of the stria terminalis (BNST). Together, these findings indicate that selected odorants can indeed block stress responses, and that odor blocking can occur via two routes: a direct route in which blocking odor signals directly inhibit CRHNs and an indirect route in which they inhibit stressor activation of neurons presynaptic to CRHNs and prevent them from transmitting stress signals to CRHNs.
Self-reported Memory Problems Eight Months after Non-Hospitalized COVID-19 in a Large Cohort
Authors: Søraas Arne , Bø Ragnhild , Kalleberg Karl Trygve , Ellingjord-Dale Merete , Landrø Nils Inge 
Published: February 2021

AbstractBackgroundNeurological manifestations of COVID-19 range from ageusia and anosmia, experienced by most patients, to altered consciousness and rare and severe encephalopathy. A direct affection of the central nervous system (CNS) in the disease has been supported by animal models and MRI findings in patients with mild and severe symptoms. Here we report eight-month data on memory problems for non-hospitalized COVID-19 patients compared to SARS-CoV-2 negative patients and untested volunteers.ObjectiveTo explore the association between non-hospitalized COVID-19 eight months previously and self-reported memory problems.MethodsWe followed a cohort of 13156 participants that was invited after (1) being tested for SARS-CoV-2 with a combined oropharyngeal- and nasopharyngeal swab or (2) randomly selected from the Norwegian population (untested). Participants completed online baseline- and follow-up questionnaires detailing underlying medical conditions, demographics, symptoms, and items from the RAND-36 questionnaire on health-related quality of life and known confounders for memory problems.ResultsAfter repeated invitations, the participation rate was 40% (N=794) of SARS-CoV-2 positive, 26% (N=7993) of negative, and 22% (N=4369) of untested randomly selected invitees. All participants completed the baseline questionnaire as a part of inclusion.The follow-up period was 248 days (SD=18) from baseline, and the follow-up questionnaire was completed by 75% of SARS-CoV-2 positive participants, 65% of negative participants, and 73% of untested randomly selected participants.At follow-up, 49 (11.5%) of the SARS-CoV-2 positive participants reported memory problems in contrast to 173 (4.1%) of the SARS-CoV-2 negative participants and 65 (2.4%) of the untested randomly selected participants.In a multivariate model, SARS-CoV-2 positivity remained strongly associated with reporting memory problems at eight months follow-up compared to the SARS-CoV-2 negative group (odds ratio (OR) 4.0, 95% confidence interval (CI) 2.8-5.2) and the untested group (OR 4.9, 95% CI 3.4-7.2).Compared to the other groups, SARS-CoV-2 positive participants also reported more concentration problems and a significant worsening of health compared to one year ago at follow-up. Feeling depressed, less energy, or pain were reported relatively equally by the different groups.SummaryWe find that 11.5% of COVID-19 patients experience memory problems eight months after the disease. SARS-CoV-2 is a new virus, and the long-term consequences of infections are therefore unknown. Our results show that a relatively high proportion of non-hospitalized COVID-19 patients report memory problems eight months after the disease.
The plant immune receptors NRG1.1 and ADR1 are calcium influx channels
Authors: Jacob Pierre , Kim Nak Hyun , Wu Feihua , El-Kasmi Farid , Walton William G. , Furzer Oliver J. , Lietzan Adam D. , Sunil Sruthi , Kempthorn Korina , Redinbo Matthew R. , Pei Zhen-Ming , Wan Li , Dangl Jeffery L. 
Published: February 2021

AbstractPlant nucleotide-binding leucine-rich repeat receptors (NLRs) regulate immunity and cell death. RPW8 domain-containing “helper” NLRs (RNLs) are required by many “sensor” NLRs. Our crystal structure of the RNL N REQUIREMENT GENE 1.1 (NRG1.1) N-terminal signaling domain resembled that of the resting state plant resistosome-forming HOPZ-ACTIVATED RESISTANCE 1 (ZAR1) and the animal MIXED-LINEAGE KINASE-LIKE (MLKL) cation channel. Active NRG1.1 oligomerized, was enriched in plasma membrane puncta and conferred cytoplasmic Ca2+influx in plant and human HeLa cells. NRG1.1-dependent Ca2+influx and cell death were sensitive to Ca2+channel blockers. Ca2+influx and cell death mediated by NRG1.1 and ACTIVATED DISEASE RESISTANCE 1 (ADR1), another RNL, required conserved negatively charged N-terminal residues. Thus, RNLs apparently form influx channels to directly regulate cytoplasmic [Ca2+] and consequent cell death.One Sentence SummaryA specific class of plant immune receptors function as calcium-permeable channels upon activation to induce cell death.
Chronos: a CRISPR cell population dynamics model
Authors: Dempster Joshua M. , Boyle Isabella , Vazquez Francisca , Root David , Boehm Jesse S. , Hahn William C. , Tsherniak Aviad , McFarland James M. 
Published: February 2021

AbstractCRISPR loss of function screens are a powerful tool to interrogate cancer biology but are known to exhibit a number of biases and artifacts that can confound the results, such as DNA cutting toxicity, incomplete phenotype penetrance and screen quality bias. Computational methods that more faithfully model the CRISPR biological experiment could more effectively extract the biology of interest than typical current methods. Here we introduce Chronos, an algorithm for inferring gene knockout fitness effects based on an explicit model of the dynamics of cell proliferation after CRISPR gene knockout. Chronos is able to exploit longitudinal CRISPR data for improved inference. Additionally, it accounts for multiple sources of bias and can effectively share information across screens when jointly analyzing large datasets such as Project Achilles and Score. We show that Chronos outperforms competing methods across a range of performance metrics in multiple types of experiments.
Structural and molecular characterization of theRpv3locus towards the development of KASP markers for downy mildew resistance in grapevine (Vitisspp.)
Authors: Wairich Andriele , Malabarba Jaiana , Buffon Vanessa , Porto Diogo Denardi , Togawa Roberto , Revers Luís F. 
Published: February 2021

AbstractPlasmopara viticolais the oomycete that causes downy mildew in grapevine. Varying levels of resistance toP. viticolaacross grape cultivars allowed quantitative trait loci to be identified. TheRpv3locus is located at chromosome 18, in a region enriched in TIR-NBS-LRR genes, and the phenotype associated is a high hypersensitive response. In this work, we aimed to identify candidate genes associated with resistance to downy mildew on theRpv3locus and to evaluate their transcriptional profiles in a susceptible and a resistant grapevine cultivar after challenging withP. viticola. Candidate genes were identified by representational differential analysis and also by functional enrichment tests. Many predicted genes associated with resistance to diseases were found at theRpv3locus. In total, seventeen genes were evaluated by RT-qPCR. Differences in the steady-state expression of these genes were observed between the two cultivars. Four genes were found to be expressed only in Villard Blanc, suggesting their association to the hypersensitivity reaction. Concerning marker assisted-selection for downy mildew resistance, we show the efficient use of a haplotype of SSR markers. Furthermore, based onRpv3-located SNPs between grapevine cultivars contrasting in downy mildew resistance, we developed and tested forty-one new markers for assisted selection. After genotypic and phenotypic evaluations on segregant populations, two markers, Rpv3_15 and Rpv3_33, were considered efficient for downy mildew resistance identification. This study constitutes an in-depth genomic characterization of theRpv3locus, confirms its involvement in resistance againstP. viticolainfection and presents promising biotechnological tools for the selection of young resistant individuals.
Impaired activation of Transposable Elements in SARS-CoV-2 infection
Authors: Sorek Matan , Meshorer Eran , Schlesinger Sharon 
Published: February 2021

AbstractTransposable element (TE) transcription is induced in response to viral infections. TE induction triggers a robust and durable interferon (IFN) response, providing a host defense mechanism. Still, the connection between SARS-CoV-2 IFN response and TEs remains largely unknown. Here, we analyzed TE expression changes in response to SARS-CoV-2 infection in different human cellular models. We find that compared to other viruses, which cause global upregulation of TEs, SARS-CoV-2 infection results in a significantly milder TE response in both primary lung epithelial cells and in iPSC-derived lung alveolar type 2 cells. TE activation precedes, and correlates with, the induction of IFN-related genes, suggesting that the limited activation of TEs following SARS-CoV-2 infection may be the reason for the weak IFN response. Diminished TE activation was not observed in lung cancer cell lines with very high viral load. Moreover, we identify two variables which explain most of the observed diverseness in immune responses: basal expression levels of TEs in the pre-infected cells, and the viral load. Finally, analyzing the SARS-CoV-2 interactome, as well as the epigenetic landscape around the TEs that are activated following infection, we identify SARS-CoV-2 interacting proteins, which may regulate chromatin structure and TE transcription in response to a high viral load. This work provides a functional explanation for SARS-CoV-2’s success in its fight against the host immune system, and suggests that TEs could be used as sensors and serve as potential drug targets for COVID-19.Key pointsUnlike other viruses, SARS-CoV-2 invokes a weak and inefficient transposable element (TE) responseTE induction precedes and predicts IFN responseBasal TE expression and viral load explain immune responsesDistinct chromatin and enhancer binding factors occupancy on TEs induced by SARS-CoV-2
Tissue-resident, extravascular CD64-Ly6C-population forms a critical barrier for inflammation in the synovium
Authors: Montgomery Anna B. , Chen Shang Yang , Gadhvi Gaurav , Mayr Maximilian G. , Cuda Carla M , Dominguez Salina , Makinde Hadijat-Kubura Moradeke , Misharin Alexander , Gurra Miranda G. , Akbarpour Mahzad , Bharat Ankit , Budinger G. R. Scott , Winter Deborah R. , Perlman Harris 
Published: February 2021

AbstractMonocytes are one of the most abundant immune cells infiltrating the inflamed organs. However, the majority of studies on monocytes focus on circulating cells, rather than those in the tissue. Here, we identify and characterize an intravascular (i.v.) and extravascular (e.v.) synovial population (Syn Ly6C-cells) which lack cell surface markers of classical monocytes (Ly6C and CD62) or tissue macrophages (CD64 and Tim4), are transcriptionally distinct and conserved in RA patients. e.v. Syn Ly6C-cells are independent of NR4A1 and CCR2, long-lived and embryonically derived while the i.v. Syn Ly6C-cells are dependent on NR4A1, short lived and derived from circulating NCM. e.v. Syn Ly6C-cells undergo increased proliferation and reverse diapedesis dependent on LFA1 in response to arthrogenic stimuli and are required for the development of RA-like disease. These findings uncover a new facet of mononuclear cell biology and are imperative to understanding tissue-resident myeloid cell function in RA.
Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2
Authors: Penner Robert 
Published: February 2021

AbstractNew tools developed by Moderna, BioNTech/Pfizer, and Oxford/Astrazeneca, among others, provide universal solutions to previously problematic aspects of drug or vaccine delivery, uptake and toxicity, portending new tools across the medical sciences. A novel method is presented based on estimating protein backbone free energy via geometry to predict effective antiviral targets, antigens and vaccine cargos that are resistant to viral mutation. This method, partly described in earlier work of the author, is reviewed and reformulated here in light of the recent proliferation of structural data on the SARS-CoV-2 spike glycoprotein and its latest mutations in the variants of concern and several further variants of interest including all international lineages. Particular attention to structures computed with Cryo Electron Microscopy allows the novel approach of probing the pH dependence of free energy in order to infer function. Key findings include: collections of recurring mutagenic residues occur across strains, presumably through cooperative convergent evolution; the preponderance of mutagenic residues do not participate in backbone hydrogen bonds; metastability of the spike glycoprotein limits the change of free energy from before to after mutation and thereby constrains selective pressure; and there are mRNA or virus-vector cargos which target low free energy peptides proximal to conserved high free energy peptides providing specific recipes for vaccines with greater specificity than the current full-spike approach. These results serve to limit peptides in the spike glycoprotein with high mutagenic potential and thereby provide a priori constraints on viral and attendant vaccine evolution. Scientific and regulatory challenges to nucleic acid therapeutic and vaccine development and deployment are finally discussed.
A precise and general FRET-based method for monitoring structural transitions in protein self-organization
Authors: Wan Qi , Mouton Sara N. , Veenhoff Liesbeth M. , Boersma Arnold J. 
Published: February 2021

AbstractProteins assemble into a tremendous variety of dynamic and functional structures. Sensitive measurements directly in cells with a high spatiotemporal resolution are needed to distinguish these different assemblies. Here, we demonstrate precise and continuous monitoring of cytoplasmic protein self-assemblies and their structural transitions. Intermolecular FRET with both the donor and acceptor protein at the same target protein provides high sensitivity while retaining the advantage of straightforward ratiometric imaging. We measure different assembly structures, transient intermediate states’ kinetics, and assembly formation resolved in space and time. Specifically, the method recapitulates that i) the mutant Huntingtin exon1 (mHttex1) protein first forms low-FRET and presumably less ordered assemblies in yeast and human cells, which develop into high-FRET aggregates, ii) the chaperone DNAJB6b prevents low-FRET mHttex1 assemblies, yet coassembles with mHttex1 aggregates, and iii) FUS’ condensates have mutation-dependent nanoscopic structures. FACS measurements allow assembly measurement in a high-throughput manner crucial for screening efforts, while fluorescence microscopy provides spatiotemporally-resolved measurements on the single-condensate level during a cell’s lifetime to assess the biological consequences. Implementation in other native or non-native proteins could provide insight into many studies involving protein condensation or aggregation.
Low-input ATAC&mRNA-Seq: a simple and robust method for simultaneous dual-omics profiling with low cell number
Authors: Li Ruifang , Grimm Sara A , Wade Paul A 
Published: February 2021

AbstractDeciphering epigenetic regulation of gene expression requires measuring the epigenome and transcriptome jointly. Single-cell multi-omics technologies have been developed for concurrent profiling of chromatin accessibility and gene expression. However, multi-omics profiling of low-input bulk samples remains challenging. Therefore, we developed low-input ATAC&mRNA-seq, a simple and robust method for studying the role of chromatin structure in gene regulation in a single experiment with thousands of cells, to maximize insights from limited input material by obtaining ATAC-seq and mRNA-seq data simultaneously from the same cells with data quality comparable to conventional mono-omics assays. Integrative data analysis revealed similar strong association between promoter accessibility and gene expression using the data of low-input ATAC&mRNA-seq as using single-assay data, underscoring the accuracy and reliability of our dual-omics assay to generate both data types simultaneously with just thousands of cells. We envision our method to be widely applied in many biological disciplines with limited materials.