bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enumerating asymptomatic COVID-19 cases and estimating SARS-CoV-2 fecal shedding rates via wastewater-based epidemiology
Authors: Schmitz Bradley W. , Innes Gabriel K. , Prasek Sarah M. , Betancourt Walter Q. , Stark Erika R. , Foster Aidan R. , Abraham Alison G. , Gerba Charles P. , Pepper Ian L. 
Published: April 2021

AbstractWastewater-based epidemiology (WBE) was utilized to monitor SARS-CoV-2 RNA in sewage collected from manholes specific to individual student dormitories (dorms) at the University of Arizona in the fall semester of 2020, which led to successful identification and reduction of transmission events. Positive wastewater samples triggered clinical testing of almost all residents within that dorm; thus, SARS-CoV-2 infected individuals were identified regardless of symptom expression. This current study examined clinical testing data to determine the abundance of asymptomatic versus symptomatic cases in these defined communities. Nasal and nasopharyngeal swab samples processed via antigen and PCR tests indicated that 79.2% of SARS-CoV-2 infections were asymptomatic, and only 20.8% of positive cases reported COVID- 19 symptoms at the time of testing. Clinical data was paired with corresponding wastewater virus concentrations, which enabled calculation of viral shedding rates in feces per infected person(s). Mean shedding rates averaged from positive wastewater samples across all dorms were 6.84 ± 0.77 log10 genome copies per gram of feces (gc/g-feces) based on the N1 gene and 7.74 ± 0.53 log10 gc/g-feces based on the N2 gene. Quantification of SARS-CoV-2 fecal shedding rates from infected persons has been the critical missing component necessary for WBE models to measure and predict SARS-CoV-2 infection prevalence in communities. The findings from this study can be utilized to create models that can be used to inform public health prevention and response actions.HighlightsWastewater-based epidemiology with clinical testing monitored SARS-CoV-2 in dorms.79.2% of SARS-CoV-2 infections were asymptomatic, and 20.8% were symptomatic.Clinical and wastewater data aggregated to estimate SARS-CoV-2 fecal shedding rate.Mean fecal shedding rate based on the N1 gene was 6.84 ± 0.77 log10 gc/g-feces.Mean fecal shedding rate based on the N2 gene was 7.74 ± 0.53 log10 gc/g-feces.Graphical Abstract
Effect of RNA on morphology and dynamics of membraneless organelles
Authors: Ranganathan Srivastav , Shakhnovich Eugene 
Published: April 2021

AbstractMembraneless organelles (MLOs) are spatiotemporally regulated structures that concentrate multi-valent proteins or RNA, often in response to stress. The proteins enriched within MLOs are often classified as high-valency “scaffolds” or low valency “clients”, with the former being associated with a phase-separation promoting role. In this study, we employ a minimal model for P-body components, with a defined protein-protein interaction network, to study their phase-separation at biologically realistic low protein concentrations. Without RNA multivalent proteins can assemble into solid-like clusters only in the regime of high concentration and stable interactions. RNA molecules promote cluster formation in an RNA-length dependent manner, even in the regime of weak interactions and low protein volume fraction. Our simulations reveal that long RNA chains act as super-scaffolds that stabilize large RNA-protein clusters by recruiting low-valency proteins within them while also ensuring functional “liquid-like” turnover of components. Our results suggest that RNA-mediated phase separation could be a plausible mechanism for spatiotemporally regulated phase-separation in the cell.
Gel Electrophoresis/Electroelution Sorting Fractionator combined with Filter Aided Sample preparation (FASP) for deep proteomic analysis
Authors: Ramos Yassel , Almeida Alexis , Carpio Jenis , Rodríguez-Ulloa Arielis , Perera Yasser , González Luis J. , Wiśniewski Jacek R. , Besada Vladimir 
Published: April 2021

AbstractSample preparation and protein fractionation are important issues in proteomic studies in spite of the technological achievements on protein mass spectrometry. Protein extraction procedures strongly affect the performance of fractionation methods by provoking protein dispersion in several fractions. The most notable exception is SDS-PAGE-based protein fractionation due to its extraordinary resolution and the effectiveness of SDS as a solubilizing agent. Its main limitation lies in the poor recovery of the gel-trapped proteins, where protein electro-elution is the most successful approach to overcome this drawback. We created a device to separate complex mixture of proteins and peptides (named “GEES fractionator”) that is based on the continuousGelElectrophoresis/Electro-elutionSorting of these molecules. In an unsupervised process, complex mixtures of proteins or peptides are fractionated into the gel while separated fractions are simultaneously and sequentially electro-eluted to the solution containing wells. The performance of the device was studied for SDS-PAGE-based protein fractionation in terms of reproducibility, protein recovery and loading capacity. In the SDS-free PAGE setup, complex peptide mixtures can also be fractionated. More than 11 700 proteins were identified in the whole-cell lysate of the CaSki cell line by using the GEES fractionator combined with the Filter Aided Sample Preparation (FASP) method and mass spectrometry analysis. GEES-based proteome characterization shows a 1.7 fold increase in the number of identified proteins compared to the unfractionated sample analysis. Proteins involved in the co-regulated transcription activity, as well as cancer related pathways such as apoptosis signaling, P53 and RAS pathways are more represented in the protein identification output of GEES-based fractionation approaches.
4 SPECIES OF BACTERIA DETERMINISTICALLY FORM A STABLE BIOFILM IN A MILLIFLUIDIC CHANNEL: ASSEMBLY PRINCIPLES
Authors: Monmeyran A. , Benyoussef W. , Thomen P. , Dahmane N. , Baliarda A. , Jules M. , Aymerich S. , Henry N. 
Published: April 2021

AbstractMultispecies microbial adherent communities are widespread in nature and organisms but the principles of their assembly and development remain unclear. Yet, the demand to understand and predict the responses of such living communities to environmental changes is increasing, calling for new approaches. Here, we test the possibility to establish a simplified but relevant model of multispecies biofilm in a laboratory setup enablingin situreal-time monitoring of the community development and control of the environmental parameters in order to decipher the mechanisms underlying the formation of the community. Using video-microscopy and species combinatorial approach, we assess the global and individual species spatiotemporal development in millifluidic channels under constant flow of nutrients. Based on quantitative measurements of expansion kinetics, local dynamics and spatial distribution, we demonstrate that the four chosen species (Bacillus thuringiensis, Pseudomonas fluorescens, Kocuria variansandRhodocyclussp.) form a dynamical community that deterministically reaches its equilibrium after about 30 hours of growth. We evidence the emergence of complexity in this simplified community as reported by spatial heterogeneity rise and non-monotonic developmental kinetics. We find interspecies interactions consisting in competition for resources — in particular oxygen — and both direct and indirect physical interactions but no positive feedback. Thereby, we introduce a model of multispecies adherent community where effective couplings result from individual species quest for fitness optimization in a moving and heterogenous environment. This control and the understanding of this simplified experimental model shall open new avenues to apprehend adherent bacterial communities behavior in a context of rapid global change.
Genomic analysis reveals a polygenic architecture of antler morphology in wild red deer (Cervus elaphus)
Authors: Peters Lucy , Huisman Jisca , Kruuk Loeske E.B. , Pemberton Josephine M. , Johnston Susan E. 
Published: April 2021

AbstractSexually-selected traits show large variation and rapid evolution across the animal kingdom, yet genetic variation often persists within populations despite apparent directional selection. A key step in solving this long-standing paradox is to determine the genetic architecture of sexually-selected traits to understand evolutionary drivers and constraints at the genomic level. Antlers are a form of sexual weaponry in male red deer. On the island of Rum, Scotland, males with larger antlers have increased breeding success, yet there has been no response to selection observed at the genetic level. To better understand the underlying mechanisms of this observation, we investigate the genetic architecture of ten antler traits and their principle components using genomic data from >38,000 SNPs. We estimate the heritabilities and genetic correlations of the antler traits using a genomic relatedness approach. We then use genome-wide association and haplotype-based regional heritability to identify regions of the genome underlying antler morphology, and an Empirical Bayes approach to estimate the underlying distributions of allele effect sizes. We show that antler morphology is heritable with a polygenic architecture, highly repeatable over an individual’s lifetime, and that almost all aspects are positively genetically correlated with some loci identified as having pleiotropic effects. Our findings suggest that a large mutational target and pleiotropy with traits sharing similar complex polygenic architectures are likely to contribute to the maintenance of genetic variation in antler morphology in this population.
Co-evolutionary analysis suggests a role for TLR9 in papillomavirus restriction
Authors: King Kelly , Larsen Brendan B. , Gryseels Sophie , Richet Cécile , Kraberger Simona , Jackson Robert , Worobey Michael , Harrison Joseph S. , Varsani Arvind , Doorslaer Koenraad Van 
Published: April 2021

A.AbstractUpon infection, DNA viruses can be sensed by pattern recognition receptors (PRRs) leading to the activation of type I and III interferons, aimed at blocking infection. Therefore, viruses must inhibit these signaling pathways, avoid being detected, or both. Papillomavirus virions are trafficked from early endosomes to the Golgi apparatus and wait for the onset of mitosis to complete nuclear entry. This unique subcellular trafficking strategy avoids detection by cytoplasmic PRRs, a property that may contribute to establishment of infection. However, as the capsid uncoats within acidic endosomal compartments, the viral DNA may be exposed to detection by toll-like receptor (TLR) 9. In this study we characterize two new papillomaviruses from bats and use molecular archeology to demonstrate that their genomes altered their nucleotide composition to avoid detection by TLR9, providing evidence that TLR9 acts as a PRR during papillomavirus infection. Furthermore, we demonstrate that TLR9, like other components of the innate immune system, is under evolutionary selection in bats, providing the first direct evidence for co-evolution between papillomaviruses and their hosts.
Neutralization of the anthrax toxin by antibody-mediated stapling of its membrane penetrating loop
Authors: Hoelzgen Fabian , Zalk Ran , Alcalay Ron , Schwartz Sagit Cohen , Garau Gianpiero , Shahar Anat , Mazor Ohad , Frank Gabriel A. 
Published: April 2021

AbstractAnthrax infection is associated with severe illness and high mortality. Protective antigen (PA) is the central component of the anthrax toxin, which is the main virulent factor of anthrax. Upon endocytosis, PA opens a pore in the membranes of endosomes, through which the toxin’s cytotoxic enzymes are extruded. The PA pore is formed by a cooperative conformational change where PA’s membrane-penetrating loops associate, forming a hydrophobic rim that pierces the membrane. Due to its crucial role in anthrax progression, PA is an important target of monoclonal antibodies-based therapy. cAb29 is a highly effective neutralizing antibody against PA. We determined the cryo-EM structure of PA in complex with the Fab portion of cAb29. We found that cAb29 neutralizes the toxin by clamping the membrane-penetrating loop of PA to a static region on PA’s surface, thereby preventing pore formation. Therefore, our results provide the structural basis for the antibody-based neutralization of PA and bring to focus the membrane-penetrating loop of PA as a target for the development of better anti-anthrax vaccines.
Transcriptomic stability or lability explains sensitivity to climate stressors in coralline algae
Authors: Page Tessa M. , McDougall Carmel , Bar Ido , Diaz-Pulido Guillermo 
Published: April 2021

AbstractCrustose coralline algae (CCA) are a group of calcifying red macroalgae crucial to tropical coral reefs because they form crusts that cement together the reef framework1. Previous research into the responses of CCA to ocean warming (OW) and ocean acidification (OA) have found reductions in calcification rates and survival2,3, with magnitude of effect being species-specific. Responses of CCA to OW and OA could be linked to evolutionary divergence time and/or their underlying molecular biology, the role of either being unknown in CCA. Here we showSporolithon durum, a species from an earlier diverged lineage that exhibits low sensitivity to climate stressors, had little change in metabolic performance and did not significantly alter the expression of any genes when exposed to temperature and pH perturbations. In contrast,Porolithon onkodes, a species from a recently diverged lineage, reduced photosynthetic rates and had over 400 significantly differentially expressed genes in response to experimental treatments, with differential regulation of genes relating to physiological processes. We suggest earlier diverged CCA may be resistant to OW and OA conditions predicted for 2100, whereas taxa from more recently diverged lineages with demonstrated high sensitivity to climate stressors may have limited ability for acclimatisation.
Principles of mRNA targeting via the Arabidopsis m6A-binding protein ECT2
Authors: Arribas-Hernández Laura , Rennie Sarah , Köster Tino , Porcelli Carlotta , Lewinski Martin , Staiger Dorothee , Andersson Robin , Brodersen Peter 
Published: April 2021

AbstractSpecific recognition ofN6-methyladenosine (m6A) in mRNA by RNA-binding proteins containing a YT521-B homology (YTH) domain is important in eukaryotic gene regulation. The Arabidopsis YTH-domain protein ECT2 is thought to bind to mRNA at URU(m6A)Y sites, yet RR(m6A)CH is the canonical m6A consensus site in all eukaryotes and ECT2 functions require m6A binding activity. Here, we apply iCLIP (individual-nucleotide resolution cross-linking and immunoprecipitation) and HyperTRIBE (targets of RNA-binding proteins identified by editing) to define high-quality target sets of ECT2, and analyze the patterns of enriched sequence motifs around ECT2 crosslink sites. Our analyses show that ECT2 does in fact bind to RR(m6A)CH. Pyrimidine-rich motifs are enriched around, but not at m6A-sites, reflecting a preference forN6-adenosine methylation of RRACH/GGAU islands in pyrimidine-rich regions. Such motifs, particularly oligo-U and UNUNU upstream of m6A sites, are also implicated in ECT2 binding via its intrinsically disordered region (IDR). Finally, URUAY-type motifs are enriched at ECT2 crosslink sites, but their distinct properties suggest function as sites of competition between binding of ECT2 and as yet unidentified RNA-binding proteins. Our study provides coherence between genetic and molecular studies of m6A-YTH function in plants, and reveals new insight into the mode of RNA recognition by YTH-domain-containing proteins.
Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
Authors: Kruse Thomas , Benz Caroline , Garvanska Dimitriya H. , Lindqvist Richard , Mihalic Filip , Coscia Fabian , Inturi Ravi Teja , Sayadi Ahmed , Simonetti Leandro , Nilsson Emma , Ali Muhammad , Kliche Johanna , Morro Ainhoa Moliner , Mund Andreas , Andersson Eva , McInerney Gerald , Mann Matthias , Jemth Per , Davey Norman E , Överby Anna K , Nilsson Jakob , Ivarsson Ylva 
Published: April 2021

AbstractViral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, current methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a scalable viral peptide discovery approach covering 229 RNA viruses that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction blocks SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.
Feeling documents: toward a phenomenology of information seeking
Authors: Keilty Patrick , Leazer Gregory 
Published: April 2021

PurposeThe purpose of this paper is to present two models of human cognition. The first narrow model concentrates on the mind as an information-processing apparatus, and interactions with information as altering thought structures and filling gaps in knowledge. A second model incorporates elements of unconsciousness, embodiment and affect. The selection of one model over the other, often done tacitly, has consequences for subsequent models of information seeking and use.Design/methodology/approachA close reading of embodied engagements with pornography guided by existential phenomenology.FindingsThe paper develops a phenomenology of information seeking, centered primarily around the work of Merleau-Ponty, to justify a more expansive concept of cognition. The authors demonstrate the roles of affect and embodiment in document assessment and use, with a prolonged example in the realm of browsing pornography.Originality/valueModels of information seeking and use need to account for diverse kinds of human-document interaction, to include documents such as music, film and comics that engage the emotions or are perceived through a broader band of sensory experience to include visual and auditory components. The authors consider how those human-document engagements form virtual communities based on the similarity of their members’ affective and embodied responses, which in turn inform the arrangements, through algorithms, of the relations of documents to each other. Less instrumental forms of information seeking and use – ones that incorporate elements of embodiment and affect – are characterized as esthetic experiences, following the definition of the esthetic provided by Dewey. Ultimately the authors consider, given the ubiquity of information seeking and its rhythm in everyday life, whether we can meaningfully characterize information seeking as a distinct human process.
Nicotinamide phosphoribosyltransferase inhibitor is a novel therapeutic candidate in LPS‐induced neutrophil extracellular traps
Authors: Ding Jing , Zhang Zuoman , Huang Weimin , Bi Guangliang 
Published: April 2021

AbstractNeutrophil extracellular traps (NETs) are beneficial antibacterial defense structures. However, excessive NETs have also been linked to tissue damage and organ dysfunction. LPS and Gram‐negative bacteria induce the formation of reactive oxygen species (ROS)‐dependent NETs via the JNK pathway. It was found previously that knockdown of nicotinamide phosphoribosyltransferase (NAMPT) upregulates surfactant protein B (SFTPB or SP‐B) and attenuates LPS‐induced acute lung injury (ALI) via inhibiting JNK activation. This study investigated the effect of FK866, an intracellular NAMPT inhibitor, on the formation of LPS‐induced NETs in mouse bronchoalveolar lavage (BAL) neutrophils and in differentiated HL‐60 cells. The results show that inhibition of NAMPT by FK866 suppresses NETs formation in BAL neutrophils from the mice exposed to LPS. FK866 also suppresses NETs formation in the differentiated HL‐60 cells stimulated with LPS. Additional data indicate that these effects are mediated by suppressing ROS production at least partly via inhibiting JNK activation and depleting NAD(P)H. The utility of inhibition of intracellular NAMPT may be a potential therapy for LPS‐induced NETs‐related diseases.
Dsk2 involves in conidiation, multi‐stress tolerance and thermal adaptation in Beauveria bassiana
Authors: Wang Dingyi , Lv Chao , Guan Yi , Ni Xiangyin , Wu Fuzhong 
Published: April 2021

SummaryDsk2 is a nuclear‐enriched ubiquitin‐like polyubiquitin‐binding protein that regulates protein degradation in yeast but has not been explored yet in filamentous fungi, such as Beauveria bassiana. Here, we report Beauveria bassiana Dsk2 located both in the nucleus and in cytoplasm of hyphal cells. Deletion of Dsk2 resulted in mild growth defect on scant media with various carbon/nitrogen sources and dramatic attenuation in conidiation capability at optimal condition. Compared to the wild‐type, ΔDsk2 strains are much more sensitive to high osmotic and oxidative pressure during vegetative growth. Meanwhile, the mutant strains showed an increased chemical tolerance to Congo red and calcofluor white, two cell wall perturbing agents. The transcriptional changes of genes involved in central development, superoxide dismutase and chitin synthesis pathway indicate that Dsk2 acts as a multi‐functional regulator in adapting to environmental changes. Importantly, Dsk2 negatively regulated the ability of thermal resistance in B. bassiana, which makes it a potential target gene for constructing engineering anti‐thermal strains in the circumstance of global warming. Altogether, our finding highlights novel roles of Dsk2 involved in the asexual cycle, multi‐stress tolerance and pest control potential of B. bassiana.
Oral health self‐care behaviours in serious mental illness: A systematic review and meta‐analysis
Authors: Turner Elizabeth , Berry Katherine , Aggarwal Vishal R. , Quinlivan Leah , Villanueva Timothy , Palmier‐Claus Jasper 
Published: April 2021

AbstractAimTo understand the relationship between serious mental illness and oral health self‐care behaviours using meta‐analytic methods and a narrative synthesis of available literature.MethodThe review followed the Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines [PROSPERO reference: CRD42020176779]. Search terms pertaining to serious mental illness and oral health were entered into EMBASE, PsycINFO, Medline and CINAHL. Eligible studies included a sample of people with a serious mental illness and a quantitative measure of an oral health self‐care behaviour (eg dental visits, toothbrushing). The Effective Public Health Practice Project tool was utilised to appraise the quality of the literature. Studies in the meta‐analysis contained a non‐clinical or general population comparator sample.ResultsPeople with a serious mental illness were significantly less likely to visit the dentist (OR 0.46, 95% CI 0.32–0.065, p > 0.001) or brush their teeth (OR 0.19, 95% CI 0.08–0.42, p < 0.001) when compared to non‐clinical comparator samples. Few studies explored other oral health self‐care behaviours (eg flossing and mouth washing), but uptake was generally low in people with a serious mental illness. The study quality of included studies was variable.ConclusionsThe research showed a reduced uptake of oral health self‐care behaviours in people with a serious mental illness. Suboptimal oral health can negatively impact on physical, social and psychological functioning. Further research is needed to understand the reasons for low rates of oral health self‐care behaviours in this population.