bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of miR-155 attenuates lung cytokine storm induced by SARS-CoV-2 infection in human ACE2-transgenic mice
Authors: Soni Dharmendra Kumar , Cabrera-Luque Juan , Kar Swagata , Sen Chaitali , Devaney Joseph , Biswas Roopa 
Published: December 2020

ABSTRACTCoronavirus disease 2019 (COVID-19) is a recent global pandemic. It is a deadly human viral disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with a high rate of infection, morbidity and mortality. Therefore, there is a great urgency to develop new therapies to control, treat and prevent this disease. Endogenous microRNAs (miRNAs, miRs) of the viral host are key molecules in preventing viral entry and replication, and building an antiviral cellular defense. Here, we have analyzed the role of miR-155, one of the most powerful drivers of host antiviral responses including immune and inflammatory responses, in the pathogenicity of SARS-CoV-2 infection. Subsequently, we have analyzed the potency of anti-miR-155 therapy in a COVID-19 mouse model (mice transgenic for human angiotensin I-converting enzyme 2 receptor (tg-mice hACE2)). We report for the first time that miR-155 expression is elevated in COVID-19 patients. Further, our data indicate that the viral load as well as miR-155 levels are higher in male relative to female patients. Moreover, we find that the delivery of anti-miR-155 to SARS-CoV-2-infected tg-mice hACE2 effectively suppresses miR-155 expression, and leads to improved survival and clinical scores. Importantly, anti-miR-155-treated tg-mice hACE2 infected with SARS-CoV-2 not only exhibit reduced levels of pro-inflammatory cytokines, but also have increased anti-viral and anti-inflammatory cytokine responses in the lungs. Thus, our study suggests anti-miR-155 as a novel therapy for mitigating the lung cytokine storm induced by SARS-CoV-2 infection.
Cohesin regulates homology search during recombinational DNA repair
Authors: Piazza Aurèle , Bordelet Hélène , Dumont Agnès , Thierry Agnès , Savocco Jérôme , Girard Fabien , Koszul Romain 
Published: December 2020

SummaryHomologous recombination (HR) is a ubiquitous DNA double-strand break (DSB) repair mechanism that promotes cell survival. It entails a potentially genome-wide homology search step, carried out along a conserved RecA/Rad51-ssDNA nucleoprotein filament (NPF) assembled on each DSB ends1–3. This search is subdued to NPF-dsDNA collision probability, dictated in part by chromatin conformation2,4. In contrast to the extensive knowledge about chromatin composition and mobility changes elicited by the DNA damage checkpoint (DDC)5–7, whether, how, and to which extent a DSB impacts spatial chromatin organization, and whether this organization in turns influences the homology search process, remains ill-defined8,9. Here we characterize two layers of spatial chromatin reorganization following DSB formation inS. cerevisiae.While cohesin folds chromosomes into cohesive arrays of 10-20 kb long chromatin loops as cells arrest in G2/M10,11, the DSB-flanking regions locally interact in a resection- and 9-1-1 clamp-dependent manner, independently of cohesin and HR proteins. This local structure blocks cohesin progression, constraining the extending NPF at loop base. Functionally this organization promotes side-specificcisDSB-dsDNA interactions that scales with loop expansion span, and provides a kinetic advantage for identification of intra- over inter-chromosomal homologies. We propose that cohesins regulate homology search by promotingcisdsDNA over-sampling, both upon loop expansion-coupled unidimensional dsDNA scanning, NPF trapping, and chromosome individualization, largely independent of their role in sister chromatid cohesion.
Identification of a novel conserved signaling motif in CD200 Receptor required for its inhibitory function
Authors: Timmerman Laura M. , de Graaf Fréderique , Satravelas Nikolaos , Kesmir Çan , Meyaard Linde , van der Vlist Michiel 
Published: December 2020

AbstractThe inhibitory signaling of CD200 receptor 1 (CD200R) has been attributed to its NPxY signaling motif. However, NPxY-motifs are present in multiple protein families and are mostly known to mediate protein trafficking between subcellular locations rather than signaling. Therefore, we investigated whether additional motifs specify the inhibitory function of CD200R. We performed phylogenetic analysis of the intracellular domain of CD200R in mammals, birds, bony fish, amphibians and reptiles. Indeed, the tyrosine of the NPxY-motif is fully conserved across species, in line with its central role in CD200R signaling. In contrast, P295 of the NPxY-motif is not conserved. Instead, a conserved stretch of negatively charged amino acids, EEDE279, and two conserved residues P285 and K292 in the flanking region prior to the NPxY-motif are required for CD200R mediated inhibition of p-Erk, p-Akt308, p-Akt473, p-rpS6 and LPS-induced IL-8 secretion. Altogether, we show that instead of the more common NPxY-motif, CD200R signaling can be assigned to a unique signaling motif in mammals defined by: EEDExxPYxxYxxKxNxxY.
Genotype-phenotype map of an RNA-ligand complex
Authors: Puchta Olga , Sobczyk Grzegorz , Smer-Barreto Vanessa , Ireland Hollie , Vendrell Marc , Oyarzún Diego A. , Bujnicki Janusz M. , Whyte Graeme , Kudla Grzegorz 
Published: December 2020

AbstractRNA-ligand interactions play important roles in biology and biotechnology, but they often involve complex three-dimensional folding of RNA and are difficult to predict. To systematically explore the phenotypic landscape of an RNA-ligand complex, we used microarrays to investigate all possible single and double mutants of the 49-nt RNA aptamer Broccoli bound to the fluorophore DFHBI-1T. We collected more than seven million fluorescence measurements in varying conditions, and inferred dissociation rate constants, spectral shifts, and intragenic epistasis. Our results reveal an unexpectedly complex phenotypic landscape, in which mutations near the fluorophore binding pocket modulated magnesium-, potassium- and fluorophore-binding and fluorescence spectra, while distal mutations influenced structural stability and fluorescence intensity. We trained a machine learning model that accurately predicted RNA secondary structure from local epistatic interactions, despite the presence of G-quadruplexes and other noncanonical structures. Our experimental platform will facilitate the discovery and analysis of new RNA-ligand interactions.
Seasonal niche differentiation between evolutionary closely related marine bacteria
Authors: Auladell Adrià , Barberán Albert , Logares Ramiro , Garcés Esther , Gasol Josep M. , Ferrera Isabel 
Published: December 2020

AbstractBacteria are highly dynamic in marine environments, where they play key biogeochemical roles. Here, we tested how similar the niche of closely related marine bacteria is and what are the environmental parameters modulating their ecological responses in a coastal oligotrophic time series. We further explored how conserved the niche is at broader taxonomic levels. We found that, for certain genera, niche similarity decreases as nucleotide divergence increases between closely related amplicon sequence variants, a pattern compatible with selection of similar taxa through habitat filtering. Additionally, we observed evidence of niche partitioning within various genera shown by the distinct seasonal patterns of closely related taxa. At broader levels, we did not observe coherent seasonal trends at the class level, with the order and family ranks conditioned to the patterns that exist at the genus level. This study explores the coexistence of niche overlap and niche partitioning in a coastal marine environment.
Redistribution of FLAgellar Member 8 during the trypanosome life cycle: consequences for cell fate prediction
Authors: Alvarez Estefanía Calvo , Bonnefoy Serge , Salles Audrey , Benson Fiona E. , McKean Paul G. , Bastin Philippe , Rotureau Brice 
Published: December 2020

AbstractThe single flagellum of African trypanosomes is essential in multiple aspects of the parasite development. The FLAgellar Member 8 protein (FLAM8), localised to the tip of the flagellum in cultured insect forms, was identified as a marker of the locking event that controls flagellum length. Here, we investigated whether FLAM8 could also reflect the flagellum maturation state in other stages. We observed that FLAM8 distribution extended along the entire flagellar cytoskeleton in mammalian infective forms. Then, a rapid FLAM8 concentration to the distal tip occurs during differentiation into early insect forms, illustrating for the first time the remodeling of an existing flagellum in trypanosomes. In the tsetse cardia, FLAM8 further localizes to the entire length of the new flagellum during an asymmetric division. Strikingly, in parasites dividing in the tsetse midgut and in the salivary glands, the amount and distribution of FLAM8 in the new flagellum was seen to predict the daughter cell fate. We propose and discuss how FLAM8 could be considered as a meta-marker of the flagellum stage and maturation state in trypanosomes.Summary statementThe trypanosome protein FLAM8 displays a dynamic and stage-specific distribution during the entire parasite cycle, representing a novel marker of the flagellum stage and maturation state.
Genetic correlations between COVID-19 and a variety of traits and diseases
Authors: Chang Xiao , Li Yun , Nguyen Kenny , Qu Huiqi , Liu Yichuan , Glessner Joseph , Sleiman Patrick M A , Hakonarson Hakon 
Published: December 2020

AbstractWe analyzed GWAS results released by COVID-19 Host Genetics Initiative, UK biobank and GWAS Catalog to explore the genetic overlap between COVID-19 and a broad spectrum of traits and diseases. We validate previously reported medical conditions and risk factors based on epidemiological studies, including but not limited to hypertension, type 2 diabetes and obesity. We also report novel traits associated with COVID-19, which have not been previously reported from epidemiological data, such as opioid use and educational attainment. Taken together, this study extends our understanding of the genetic basis of COVID-19, and provides target traits for further epidemiological studies.
Taranto’s long shadow? Cancer mortality shows alarming peaks for specific types in the most polluted city of Italy but also in surrounding towns
Authors: Roberto Cazzolla Gatti R. , Velichevskaya Alena 
Published: December 2020

AbstractA national-scale study in Italy showed an incidence of cancer higher in the territories indicated as highly polluted compared to the regional average. One of them, the city of Taranto in Apulia (Italy), which is considered one of the most polluted cities in Europe, has numerous industrial activities that impact population health. We studied the epidemiological effects of a high level of pollution produced by the industrial area of Taranto in increasing the mortality rate for some specific cancer types in the city and towns of the two provinces located downwind. We analysed 10-year mortality rates for 14 major types of tumours reported among the residents of Taranto, of 6 surrounding towns, randomly placed within an imaginary cone in the main wind direction from the vertex of the industrial zone of Taranto. Our results confirm our hypothesis that the mortality rate for some specific types of cancer (namely, Hodgkin and non-Hodgkin lymphomas, leukaemia, liver and bladder tumours) are higher than the norm in the municipality of Taranto and we have evidence that other local causes may be implicated in the excess of mortality besides the potential dispersal of pollutants from the industrial area of Taranto. The proximity to the industrial area of Taranto cannot, therefore, explain alone the anomalies detected in some populations. It is likely that other site-specific sources of heavy pollution are playing a role in worsening the death toll of these towns and this must be taken into serious consideration by environmental policy-makers and local authorities.
Face covering adherence is positively associated with better mental health and wellbeing: a longitudinal analysis of the CovidLife surveys
Authors: Altschul Drew , Fawns-Ritchie Chloe , Kwong Alex , Hartley Louise , Nangle Clifford , Edwards Rachel , Dawson Rebecca , Levein Christie , Campbell Archie , Flaig Robin , McIntosh Andrew , Deary Ian , Marioni Riccardo , Hayward Caroline , Sudlow Cathie , Douglas Elaine , Bell David , Porteous David 
Published: December 2020

AbstractFace masks or coverings are effective at reducing airborne infection rates, yet pandemic mitigation measures, including wearing face coverings, have been suggested to contribute to reductions in quality of life and poorer mental health. Longitudinal analyses of more than 11,000 participants across the UK found no association between lower adherence to face covering guidelines and poorer mental health. The opposite appears to be true. Even after controlling for behavioral, social, and psychological confounds, including measures of pre-pandemic mental health, individuals who wore face coverings “most of the time” or “always” had better mental health and wellbeing than those who did not. These results suggest that wearing face coverings more often will not negatively impact mental health.
Mental Disorder Prevalence Among Populations Impacted by Coronavirus Pandemics: A Multilevel Meta-Analytic Study of COVID-19, MERS & SARS
Authors: Boden Matt , Cohen Nichole , Froelich Jessilyn M. , Hoggatt Katherine J. , Magid Hoda S. Abdel , Mushiana Swapandeep S. 
Published: December 2020

AbstractObjectiveThrough a systematic review and meta-analysis of research on COVID-19, severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) pandemics, we investigated whether mental disorder prevalence: (a) was elevated among populations impacted by coronavirus pandemics (relative to unselected populations reported in the literature), and (b) varied by disorder (undifferentiated psychiatric morbidity, anxiety, depressive, posttraumatic stress disorders [PTSD]) and impacted population (community, infected/recovered, healthcare provider, quarantined).MethodFrom 68 publications (N=87,586 participants), 808 estimates were included in a series of multilevel meta-analyses/regressions including random effects to account for estimates nested within studies.ResultsMedian summary point prevalence estimates varied by disorder and population. Psychiatric morbidity (20%-56%), PTSD (10-26%) and depression (9-27%) were most prevalent in most populations. The highest prevalence of each disorder was found among infected/recovered adults (18-56%), followed by healthcare providers (11-28%) and community adults (11-20%). Prevalence estimates were often notably higher than reported for unselected samples. Sensitivity analyses demonstrated that overall prevalence estimates moderately varied by pandemic, study location, and mental disorder measure type.ConclusionCoronavirus pandemics are associated with multiple mental disorders in several impacted populations. Needed are investigations of causal links between specific pandemic-related stressors, threats, and traumas and mental disorders.
Criteria-based curation of a therapy-focused compendium to support treatment recommendations in precision oncology
Authors: Lin Frank P. , Thavaneswaran Subotheni , Grady John P. , Ballinger Mandy , Kansara Maya , Oakes Samantha R. , Desai Jayesh , Lee Chee Khoon , Simes John , Thomas David M. 
Published: December 2020

AbstractBACKGROUNDWhile several key resources exist that interpret therapeutic significance of genomic alterations in cancer, many regional real-world issues limit access to drugs. There is a need for a pragmatic, evidence-based, context-adapted tool to guide clinical management based on molecular biomarkers.METHODSA compendium of approved and experimental therapies with associated biomarkers was built following a survey of drug regulatory databases, existing knowledge bases, and published literature. Each biomarker-disease-therapy triplet was then categorized using a tiering system reflective of key therapeutic considerations: approved and reimbursed standard-of-care therapies with respect to a jurisdiction (Tier 1), evidence of efficacy or approval in another jurisdiction (Tier 2), evidence of antitumour activity (Tier 3), and plausible biological rationale (Tier 4). Two resistance categories were defined: lack of efficacy (Tier R1), and lack of antitumor activity (Tier R2).RESULTSFollowing comprehensive literature review and appraisal, we developed a curated knowledge base focused on drugs relevant and accessible in the Australian healthcare system (TOPOGRAPH: Therapy Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals). As of November 2020, TOPOGRAPH comprised 2810 biomarker-disease-therapy triplets in 989 expert-appraised entries, including 373 therapies, 199 predictive biomarkers, and 106 cancer types. In the 345 biomarker-linked therapies catalogued, 84 (24%) and 65 (19%) therapies in contexts of different cancer types have Tier 1 and 2 designations respectively, while 271 (79%) therapies were supported by preclinical studies, early clinical trials, retrospective studies, or case series (Tiers 3 and 4). A total of 119 of 373 (33%) therapies associated with biomarkers of resistance were also catalogued. A clinical algorithm was also developed to support therapeutic decision-making using predictive biomarkers. This resource is accessible online at https://topograph.info/.CONCLUSIONTOPOGRAPH is intended to support oncologists with context-appropriate clinical decision-making– optimising selection and accessibility of the most appropriate targeted therapy for any given genomic biomarker. Our approach can be readily adapted to build jurisdiction-specific resources to standardise decision-making in precision oncology.
Resolving the transcriptional transitions associated with oligodendrocyte generation from adult neural stem cells by single cell sequencing
Authors: Azim Kasum , Calzolari Filippo , Cantone Martina , Akkermann Rainer , Vera Julio , Hartung Hans-Peter , Basak Onur , Butt Arthur Morgan , Küry Patrick 
Published: December 2020

AbstractThe subventricular zone (SVZ) is the largest neurogenic niche in the adult forebrain. Notably, neural stem cells (NSCs) of the SVZ generate not only neurons, but also oligodendrocytes, the myelin-forming cells of the central nervous system. Transcriptomic studies have provided detailed knowledge of the molecular events that regulate neurogenesis, but little is understood about adult oligodendrogenesis from SVZ-NSCs. To address this, we performed in-depth single-cell transcriptomic analyses to resolve the major differences in neuronal and oligodendroglial lineages derived from the adult SVZ. A hallmark of adult oligodendrogenesis was the stage-specific expression of transcriptional modulators that regulate developmental oligodendrogenesis. Notably, divergence of the oligodendroglial lineage was distinguished by Wnt-Notch and angiogenesis-related signaling, whereas G-protein-coupled receptor signaling pathways were the major signature observed in the neurogenic lineage. Moreover, in-depth gene regulatory network analysis identified key stage-specific master regulators of the oligodendrocyte lineage and revealed new mechanisms by which signaling pathways interact with transcriptional networks to control lineage progression. Our work provides an integrated view of the multi-step differentiation process leading from NSCs to mature oligodendrocytes, by linking environmental signals to known and novel transcriptional mechanisms orchestrating oligodendrogenesis.Main pointsDistinct adult NSC populations giving rise to either oligodendrocytes or neurons can be identified by the expression of transcription factors.Gene regulatory control of oligodendrogenesis is a major fate-determinant for their generation.
Sugarcane Nitrogen and Irrigation Level Prediction Based on UAV-Captured Multispectral Images at the Elongation Stage
Authors: Li Xiuhua , Ba Yuxuan , Zhang Shimin , Nong Mengling , Zhang Muqing , Wang Ce 
Published: December 2020

AbstractIntroductionSugarcane is the main industrial crop for sugar production; its growth status is closely related to fertilizer, water, and light input. Unmanned aerial vehicle (UAV)-based multispectral imagery is widely used for high-throughput phenotyping because it can rapidly predict crop vigor. This paper mainly studied the potential of multispectral images obtained by low-altitude UAV systems in predicting canopy nitrogen (N) content and irrigation level for sugarcane.MethodsAn experiment was carried out on sugarcane fields with three irrigation levels and five nitrogen levels. A multispectral image at a height of 40 m was acquired during the elongation stage, and the canopy nitrogen content was determined as the ground truth. N prediction models, including partial least square (PLS), backpropagation neural network (BPNN), and extreme learning machine (ELM) models, were established based on different variables. A support vector machine (SVM) model was used to recognize the irrigation level.ResultsThe PLS model based on band reflectance and five vegetation indices had better accuracy (R=0.7693, root mean square error (RMSE)=0.1109) than the BPNN and ELM models. Some spectral information from the multispectral image had obviously different features among the different irrigation levels, and the SVM algorithm was used for irrigation level classification. The classification accuracy reached 77.8%.ConclusionLow-altitude multispectral images could provide effective information for N prediction and water irrigation level recognition.