bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring epitope and functional diversity of anti-SARS-CoV2 antibodies using AI-based methods
Authors: Dumet C. , Jullian Y. , Musnier A. , Rivière Ph. , Poirier N. , Watier H. , Bourquard T. , Poupon A. 
Published: December 2020

SummarySince the beginning of the COVID19 pandemics, an unprecedented research effort has been conducted to analyze the antibody responses in patients, and many trials based on passive immunotherapy — notably monoclonal antibodies — are ongoing. Twenty-one antibodies have entered clinical trials, 6 having reached phase 2/3, phase 3 or having received emergency authorization. These represent only the tip of the iceberg, since many more antibodies have been discovered and represent opportunities either for diagnosis purposes or as drug candidates. The main problem facing laboratories willing to develop such antibodies is the huge task of analyzing them and choosing the best candidate for exhaustive experimental validation. In this work we show how artificial intelligence-based methods can help in analyzing large sets of antibodies in order to determine in a few hours the best candidates in few hours. The MAbCluster method, which only requires knowledge of the amino acid sequences of the antibodies, allows to group the antibodies having the same epitope, considering only their amino acid sequences and their 3D structures (actual or predicted), and to infer some of their functional properties. We then use MAbTope to predict the epitopes for all antibodies for which they are not already known. This allows an exhaustive comparison of the available epitopes, but also gives a synthetic view of the possible combinations. Finally, we show how these results can be used to predict which antibodies might be affected by the different mutations arising in the circulating strains of the virus, such as the N501Y mutation that has started to spread in Great-Britain.
Shedding Light on Microbial Dark Matter with A Universal Language of Life
Authors: Hoarfrost A , Aptekmann A , Farfañuk G , Bromberg Y 
Published: December 2020

AbstractThe majority of microbial genomes have yet to be cultured, and most proteins predicted from microbial genomes or sequenced from the environment cannot be functionally annotated. As a result, current computational approaches to describe microbial systems rely on incomplete reference databases that cannot adequately capture the full functional diversity of the microbial tree of life, limiting our ability to model high-level features of biological sequences. The scientific community needs a means to capture the functionally and evolutionarily relevant features underlying biology, independent of our incomplete reference databases. Such a model can form the basis for transfer learning tasks, enabling downstream applications in environmental microbiology, medicine, and bioengineering. Here we present LookingGlass, a deep learning model capturing a “universal language of life”. LookingGlass encodes contextually-aware, functionally and evolutionarily relevant representations of short DNA reads, distinguishing reads of disparate function, homology, and environmental origin. We demonstrate the ability of LookingGlass to be fine-tuned to perform a range of diverse tasks: to identify novel oxidoreductases, to predict enzyme optimal temperature, and to recognize the reading frames of DNA sequence fragments. LookingGlass is the first contextually-aware, general purpose pre-trained “biological language” representation model for short-read DNA sequences. LookingGlass enables functionally relevant representations of otherwise unknown and unannotated sequences, shedding light on the microbial dark matter that dominates life on Earth.AvailabilityThe pretrained LookingGlass model and the transfer learning-derived models demonstrated in this paper are available in the LookingGlass release v1.01. The open source fastBio Github repository and python package provides classes and functions for training and fine tuning deep learning models with biological data2. Code for reproducing analyses presented in this paper are available as an open source Github repository3.
Cell-type apoptosis in lung during SARS-CoV-2 infection
Authors: Liu Yakun , Garron Tania M. , Chang Qing , Su Zhengchen , Zhou Changcheng , Gong Eric C. , Zheng Junying , Yin Yw , Ksiazek Thomas , Brasel Trevor , Jin Yang , Boor Paul , Comer Jason E. , Gong Bin 
Published: December 2020

AbstractThe SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS) following infection because fatal COVID-19 cases are commonly linked to respiratory failure due to ARDS. The pathologic alteration known as diffuse alveolar damage in endothelial and epithelial cells is a critical feature of acute lung injury in ARDS. However, the pathogenesis of ARDS following SRAS-CoV-2 infection remains largely unknown.In the present study, we examined apoptosis in post-mortem lung sections from COVID-19 patients and lung tissues from a non-human primate model of SARS-CoV-2 infection, in a cell-type manner, including type 1 and 2 alveolar cells and vascular endothelial cells (ECs), macrophages, and T cells. Multiple-target immunofluorescence (IF) assays and western blotting suggest both intrinsic and extrinsic apoptotic pathways are activated during SARS-CoV-2 infection. Furthermore, we observed that SARS-CoV-2 fails to induce apoptosis in human bronchial epithelial cells (i.e., BEAS2B cells) and primary human umbilical vein endothelial cells (HUVECs), which are refractory to SARS-CoV-2 infection. However, infection of co-cultured Vero cells and HUVECs or Vero cells and BEAS2B cells with SARS-CoV-2 induced apoptosis in both Vero cells and HUVECs/BEAS2B cells, but did not alter the permissiveness of HUVECs or BEAS2B cells to the virus. Post-exposure treatment of the co-culture of Vero cells and HUVECs with an EPAC1-specific activator ameliorated apoptosis in HUVECs. These findings may help to delineate a novel insight into the pathogenesis of ARDS following SARS-CoV-2 infection.
Preclinical drug response metric based on cellular response phenotype provides better pharmacogenomic variables with phenotype relevance
Authors: Kim Sanghyun , Hwang Sohyun 
Published: December 2020

ABSTRACTBackground and PurposeAssessment of drug response is typically performed by constructing a dose-response curve of viability and summarizing it to a representative value. However, this is limited by its dependency on the assay duration and lack of reflections regarding actual cellular response phenotypes. To resolve these limitations, we considered contribution of each response phenotype upon a drug treatment to the overall growth behavior.Experimental ApproachThe differential equation of phenotype population dynamics was solved analytically without numerical computation. By using the properly figured population dynamics, we explored how the conventional assessment method itself affects the assessment result of drug response, in the context of drug screening. Alternative phenotype metric was compared with the conventional metrics through evaluation of the publicly available drug response data.Key ResultsThe conventional assessment showed several limitations in the comparative analysis of drug response: a significant time-dependency, and ambiguities in assessment results based on a dose-response curve. Instead, the alternative phenotype metrics provide time-independent phenotype rates of change, that contain all the information of the drug response at a given dose, and better classification including the mechanism underlying growth inhibition.Conclusion and ImplicationsThe conventional dose-response curve is useful for a visual presentation of overall drug responses upon a certain molecular feature qualitatively. In contrast, the phenotype metric is better for assessing therapeutic effectiveness, and would improve preclinical pharmacogenomic analysis through its relevance to a response phenotype.Bullet point summaryWhat is already knownDrug response is investigated by constructing a dose-response curve in wide range.Conventional assessment metrics of drug response lack reflections regarding actual cellular response phenotypes.What this study addsLimitations of conventional assessments are due to time-dependency of dose-response curve and customary summarization.Phenotype metric evaluate a single dose-response that is time-independent and phenotype-relevant.Clinical significancePhenotype metric would improve pharmacogenomic analysis with better classification and phenotype-relevance of drug response.Improvement in preclinical pharmacology would bring better translation and useful information in clinical studies.
How do ecological and social environments reflect parental roles in birds? A comparative analysis
Authors: Long Xiaoyan , Liu Yang , Liker András , Weissing Franz J. , Komdeur Jan , Székely Tamás 
Published: December 2020

AbstractParental roles are highly diverse in animal taxa. Since caring is an important determinant of fitness, understanding the origin and maintenance of various parental care strategies is a key question in evolutionary biology. Here we investigate parental care patterns in birds, which exhibit a remarkable diversity of parental sex roles. By means of phylogenetically informed comparative analyses we investigate whether and how care provisioning is predicted by ecology and social environment. Making use of the most comprehensive dataset including 1101 species that represent 126 avian families, we show that sex differences in parental care are neither related to food type nor to nest type, two key ecological factors. However, we found an effect of the social environment, as males tend to care relatively more in in colonial species than in non-colonial species. Taken together, these results highlight the importance of social effects for evolution of diverse parental sex roles.
Segmentation pathway genes in the Asian citrus psyllid,Diaphorina citri
Authors: Miller Sherry , Shippy Teresa D. , Hosmani Prashant S , Flores-Gonzalez Mirella , Mueller Lukas A , Hunter Wayne B , Brown Susan J , D’elia Tom , Saha Surya 
Published: December 2020

AbstractInsects have a segmented body plan that is established during embryogenesis when the anterior-posterior (A-P) axis is divided into repeated units by a cascade of gene expression. The cascade is initiated by protein gradients created by translation of maternally provided mRNAs, localized at the anterior and posterior poles of the embryo. Particular combinations of these proteins activate specific gap genes to divide the embryo into distinct regions along the A-P axis. Gap genes then activate pair-rule genes, which are usually expressed in part of every other segment. The pair-rule genes, in turn, activate expression of segment polarity genes in a portion of each segment. The segmentation genes are generally conserved among insects, although there is considerable variation in how they are deployed. We annotated 24 segmentation gene homologs in the Asian citrus psyllid,Diaphorina citri. We identified most of the genes that were expected to be present based on known phylogenetic distribution. Two exceptions wereeagleandinvected, which are present in at least some hemipterans, but were not identified inD. citri. Many of these genes are likely to be essential forD. citridevelopment and thus may be useful targets for pest control methods.
Inferring Toll-Like Receptor induced epitope subunit vaccine candidate against SARS-CoV-2: A Reverse Vaccinology approach
Authors: Nayak Ananya , Gadnayak Ayushman , Sahoo Maheswata , Bhairappanavar Shivarudrappa B , Rout Bidyutprava , Mohanty Jatindra Nath , Das Jayashankar 
Published: December 2020

AbstractToll-Like Receptors (TLRs) are a group of Pattern Recognition Receptors (PRRs) which bind to the exogenous pathogen associated molecular patterns (PAMPs) like other PRRs; hence the main function is to sense the harmness and mediate the innate immune response to pathogens. TLRs play an important role in innate immune responses to infection. The host has evolved to use other TLR and PAMP agonists as agents to stimulate a protective inflammatory immune response against infection. Because only a small number of doses are given, TLR agonists appear to have greater potential and fewer safety concerns than other uses as vaccine adjuvants. In the present days, development of peptides targeting immune response can be approved for survival in biological monitoring systems before vaccine exposures. Peptide vaccines are easy to synthesize, more stable and relatively safe. In addition, production of peptides becomes simple, easily reproducible, fast and cost effective. Getting vaccinated against Covid-19, which has become a pandemic in the human population, is the most practical way to control the outbreak. The new coronavirus does not contain a drug or vaccine to prevent it from spreading to humans. To getting a proper vaccine candidate against the novel coronavirus, the present study used the reverse vaccinology approach by using a complete set of SARS-CoV-2 proteins; such as: Spike, Envelope, Nucleocapsid, Membrane, NSPs, and ORFs to extract the antigenic elements that produce B-cell, T-cell and IFN positive epitopes. These epitopes with precise binding to the Toll-Like receptors (1-10) have developed epitope based vaccine candidates. We have prioritized a set of epitopes based on their antigenicity, allergenicity, sequence conservation and projected population coverage world-wide. The selected epitopes were employed for in-silico docking interactions with Toll-Like receptors and molecular dynamic simulation confirmed the stability of the vaccine candidates resulting epitope of spike proteins with both the TLR 7 and 8 shows the best binding affinity. We believe that this ideal epitope vaccine candidate could enhance the immune response of the host and reduce the reinfection risk.
Computational profiling of hiPSC-derived heart organoids reveals chamber defects associated with Ebstein’s anomaly
Authors: Feng Wei , Schriever Hannah , Jiang Shan , Bais Abha , Kostka Dennis , Li Guang 
Published: December 2020

AbstractHeart organoids have the potential to generate primary heart-like anatomical structures and hold great promise as in vitro models for cardiac disease. However, their properties have not yet been carefully studied, which hinders a wider spread application. Here we report the development of differentiation systems for ventricular and atrial heart organoids, enabling the study of heart disease with chamber defects. We show that our systems generate organoids comprising of major cardiac cell types, and we used single cell RNA sequencing together with sample multiplexing to characterize the cells we generate. To that end, we also developed a machine learning label transfer approach lever-aging cell type, chamber, and laterality annotations available for primary human fetal heart cells. We then used this model to analyze organoid cells from an isogeneic line carrying an Ebstein’s anomaly associated genetic variant, and we successfully recapitulated the disease’s atrialized ventricular defects. In summary, we have established a workflow integrating heart organoids and computational analysis to model heart development in normal and disease states.
TaxOnTree: a tool that generates trees annotated with taxonomic information
Authors: Sakamoto Tetsu , Ortega J. Miguel 
Published: December 2020

AbstractPhylogenetic analysis is a widely used approach for analyzing and illustrating gene/protein/species evolution and is being benefited by the increasing number of species with their DNA/genome sequenced. Generating a phylogenetic tree with sequences from hundreds of species can be considered a routine task. However, tree visualization has been challenged to organize and bring by accessible means relevant information, e.g. taxonomy, about the sampled genes/proteins. Here we present TaxOnTree, a computational tool that incorporates and allows a quick accession of the taxonomic information of samples in a phylogenetic tree. TaxOnTree takes as input a single phylogenetic tree in Newick format containing gene/protein identifiers from NCBI or Uniprot databases in their leaves but TaxOnTree also allows users to have as input a protein identifier, a single protein in FASTA, a list of protein accessions, or a(n) (un)aligned multi-FASTA file. Non-tree inputs are submitted to a phylogenetic reconstruction pipeline implemented into TaxOnTree. The tree provided by the user or generated by the pipeline is converted to Nexus format and then automatically annotated with the taxonomic information of each sample comprising the tree. The taxonomic information is retrieved by web requests from NCBI or Uniprot servers or from a local MySQL database and annotated as tags in the tree nodes. The final tree archive is in Nexus format and should be opened with FigTree software which allows visual inspection, by branch coloring or tip/node labeling, of the taxonomic information incorporated in the tree. TaxOnTree provides prompt inspection of the taxonomic distribution of orthologs and paralogs. It can be used for manual curation of taxonomic/phylogenetic scenarios and coupled to any tool that links homologous sequences to a seed sequence. TaxOnTree provides computational support to help users to inspect phylogenetic trees with a taxonomic view, even without being taxonomy experts. TaxOnTree is available athttp://bioinfo.icb.ufmg.br/taxontree.
Bottom‐up effect of eradications: The unintended consequences for top‐order predators when eradicating invasive prey
Authors: Travers Toby , Lea Mary‐Anne , Alderman Rachael , Terauds Aleks , Shaw Justine 
Published: December 2020

Abstract

The eradication of invasive species from islands yields significant conservation returns. However, novel challenges continue to arise as projects expand in their scope, complexity and scale. Prey‐loss and secondary poisoning were historically considered to have limited impact on native top‐order predators when planning eradications, but this has rarely been tested quantitatively.

We used a 10‐year timeseries of Brown Skua Stercorarius antarcticus lonnbergi breeding surveys and isotopic dietary analysis on Macquarie Island to investigate how prey‐loss and secondary poisoning deaths resulting from the eradication of an abundant invasive prey species, European rabbits Oryctolagus cuniculus, affected a top‐order predator.

Skua nest density declined from 7.14 nests/km2 (95% CI: 6.01–8.27) in the presence of rabbits (pre‐eradication) to 3.73 nests/km2 (95% CI: 2.96–4.51) in the first 3 years after the eradication of rabbits, before showing signs of recovery in the 4 years thereafter. However, breeding success dropped from 1.01 chicks/nest (95% CI: 0.76–1.26) to as low as 0.38 chicks/nest (95% CI: 0.23–0.53) with little evidence of recovery.

Secondary poisoning affected a greater number of skuas than anticipated prior to the eradication, including skuas nesting in areas where rabbits were not typically hunted as prey. We highlight that invasive prey often replace native prey in the diet of native predators rather than provide an additional source of food, and rapid eradication of non‐native prey can have long‐term impacts for predators, particularly when recovery of native prey is slow.

Synthesis and applications. Monitoring programmes that complement large‐scale eradication projects and address (a) trophic‐driven declines in predator populations and (b) population‐level impacts of secondary poisoning are integral to ensuring bottom‐up effects of eradications are anticipated and adequately quantified. If prey deficits caused by eradication of invasive prey are expected to be severe but short‐lived, supplementary feeding programmes may buffer against increased predation pressure on native prey and reduced breeding success of native predators. Alternatively, if the rapid recovery of native prey is not expected to occur naturally, breeding programmes and translocation of native prey prior to assist recovery of native predators should be considered to support ecosystem restoration.
From Socialist Subject to Capitalist Object: Industry Enclave Life Past and Present in Wuhan
Authors: Phelps Nicholas A. , Miao Julie T. , Li Zhigang , Lin Sainan 
Published: December 2020

AbstractThere is no better place to explore the relationship of industry enclaves to urban life than China, where traditionaldanweis(work units) have coexisted with new foreign direct investment enclaves. Here we draw on original interviews with workers at Wuhan Iron and Steel Company (WISCO) and Foxconn in the city of Wuhan to examine industry enclaves old and new in terms of their spatial arrangement, work, institutions, and social life and identity. The article is one of the first to integrate urban and economic geographical perspectives on the subject of enclaves. It provides evidence of similarities and contrasts in the spatial arrangement of work, institutions, life and identity centred on industry enclaves old and new. These contrasts reflect wider relations between the state and the market and between social subject and commodified labour in China. In conclusion, we identify several research directions concerning the scale, diversity and reach of urban enclavism in China and beyond.
Social Representations of Sociopolitical Groups on r/The_Donald and Emergent Conflict Narratives: A Qualitative Content Analysis
Authors: McLamore Quinnehtukqut , Uluğ Özden Melis 
Published: December 2020

AbstractSocial media has been integral for the organization and success of right‐wing populist movements in the United States and Europe. Within online communities, discussions take place in which ideologies are formulated, iterated upon, and disseminated. One particular forum, hosted on the popular website reddit.com, r/The_Donald, has received media attention for its political influence. Despite the influence of online spaces in populist, far‐right movements, relatively little attention has been paid to qualitative content of discussions that take place within such spaces, including r/The_Donald. Guided by a social representations approach, we analyzed how discussions on r/The_Donald represent sociopolitical groups. We focused on discussions of political affiliations, race relations, immigration, and culture. From a dataset of 8,198 posts, we selected 1,292 segments from 883 unique Reddit usernames and analyzed them using qualitative content analysis. The results showed that the majority of posts discussed liberals, race relations, and conspiracy theories, and in these posts, liberals and liberal ideas were delegitimized and mocked through their representations. These posts represented conservatives through antinomic contrast and comparison to liberals and liberal policies. The meanings of those representations in intergroup relations are discussed.
Oral management with mouthguards during the mixed dentition period: A case report
Authors: Otsugu Masatoshi , Suehiro Yuto , Hanaoka Issei , Okawa Rena , Nakano Kazuhiko 
Published: December 2020

AbstractCustom‐made mouthguards are widely used by athletes during training and sporting events for the prevention of oral injuries. However, even though the prevalence of dental injuries in children in the primary or mixed dentition stages is high, few reports have focused on mouthguard use for such cases due to the difficulties associated with adapting them as teeth are lost and replaced. This report presents a case of a Japanese boy in the mixed dentition stage with a custom‐made mouthguard. For fabrication, self‐curing acrylic resin was used to fill portions of a working model to keep space for the later eruption of permanent teeth. However, adjustment was necessary when gingival swelling occurred in association with maxillary canine eruption, after which refabrication was necessary. Regular management of a custom‐made mouthguard by the attending dentist is important for children in the mixed dentition period, especially during maxillary canine eruption, which causes drastic dentition changes. In the present case, custom‐made mouthguards were fully effective based on the prediction of changes in the dentition and with regular dental management.