bluuebunny/crossref_metadata_2025_split huggingface dataset:
An image-computable model on how endogenous and exogenous attention differentially alter visual perception
Authors: Jigo Michael , Heeger David J. , Carrasco Marisa 
Published: January 2021

ABSTRACTAttention alters perception across the visual field. Typically, endogenous (voluntary) and exogenous (involuntary) attention similarly improve performance in many visual tasks, but they have differential effects in some tasks. Extant models of visual attention assume that the effects of these two types of attention are identical and consequently do not explain differences between them. Here, we develop a model of spatial resolution and attention that distinguishes between endogenous and exogenous attention. We focus on texture-based segmentation as a model system because it has revealed a clear dissociation between both attention types. For a texture for which performance peaks at parafoveal locations, endogenous attention improves performance across eccentricity, whereas exogenous attention improves performance where the resolution is low (peripheral locations) but impairs it where the resolution is high (foveal locations) for the scale of the texture. Our model emulates sensory encoding to segment figures from their background and predict behavioral performance. To explain attentional effects, endogenous and exogenous attention require separate operating regimes across visual detail (spatial frequency). Our model reproduces behavioral performance across several experiments and simultaneously resolves three unexplained phenomena: (1) the parafoveal advantage in segmentation, (2) the uniform improvements across eccentricity by endogenous attention and (3) the peripheral improvements and foveal impairments by exogenous attention. Overall, we unveil a computational dissociation between each attention type and provide a generalizable framework for predicting their effects on perception across the visual field.
Predicting the Specificity-Determining Positions of Paralogous Complexes
Authors: Karakulak Tülay , Rifaioglu Ahmet Sureyya , Rodrigues João P.G.L.M. , Karaca Ezgi 
Published: January 2021

ABSTRACTDue to its clinical relevance, modulation of functionally relevant amino acids in protein-protein complexes has attracted a great deal of attention. To this end, many approaches have been proposed to predict partner-selecting, i.e., specificity-determining positions in evolutionarily close complexes. These approaches can be grouped into sequence-based machine learning and structure-based energy-driven methods. In this work, we assessed these methods’ ability to map the specificity-determining positions of Axl, a receptor tyrosine kinase involved in cancer progression and immune-related diseases. For this, we used three sequence-based predictors – SDPred, Multi-RELIEF, and Sequence Harmony – and a structure-based approach by utilizing HADDOCK and extensive molecular dynamics simulations. As a result, we show that (i) sequence-based methods overpredict the number of specificity-determining positions for Axl complexes and that (ii) combining sequence-based approaches with HADDOCK provides the most coherent set of predictions. Our work lays out a critical study on the comparative performance specificity-determining position predictors. It also presents a combined sequence-structure-based approach, which can guide the development of therapeutic molecules capable of combatting Axl misregulation in different types of diseases.
A hierarchical Bayesian model to investigate trade-offs between growth and reproduction in a long-lived plant
Authors: Journé Valentin , Papaïx Julien , Walker Emily , Courbet François , Lefèvre François , Oddou-Muratorio Sylvie , Davi Hendrik 
Published: January 2021

1AbstractA trade-off between growth and fecundity, reflecting the inability of simultaneously investing in both functions when resources are limited, is a fundamental feature of life history theory. This particular trade-off is the result of evolutionary and environmental constrains shaping reproductive and growth traits, but it remains difficult to pinpoint in natural populations of long-lived plants. We developed a hierarchical Bayesian model to estimate the inter-individual correlation among growth and reproduction, using observations at individual level over several years combined with resource simulations from an ecophysiological-based model (CASTANEA). In the Bayesian model, the resource, simulated by CASTANEA and incorporated as a latent variable, is allocated to tree growth, reproductive buds initiation and fruit maturation. Then, we used individual random effects correlated among energetic sinks to investigate potential trade-offs. We applied this original approach to a Mediterranean coniferous tree, Atlas Cedar (Cedrus atlantica), at two contrasted levels of competition, high versus low density population. We found that trees initializing many reproductive buds had a higher growth. Moreover, a negative correlation was detected between growth and fruit survival during maturation. Finally, trees investing more resource to maturate fruits initiated less reproductive buds. The level of competition did not impact the sign of these three correlations, but changed the level of resource allocation: low density population favored growth whereas high density favored reproduction. The level of resource have an impact on individual strategies. This new modeling framework allowed us to detect various individual strategies of resource allocation to growth versus late-stage reproduction on the one hand, and to early-versus late-stage reproduction on the other hand. Moreover, the sign of the correlation between growth and reproductive traits depends on the stage of reproduction considered. Hence, we suggest that the investigation of potential trade-offs between growth and reproduction requires to integrate the dynamics of resource and sink’s phenology, from initiation to maturation of reproductive organs.
Somatic mutations reveal widespread mosaicism and mutagenesis in human placentas
Authors: Coorens Tim H. H. , Oliver Thomas R. W. , Sanghvi Rashesh , Sovio Ulla , Cook Emma , Vento-Tormo Roser , Haniffa Muzlifah , Young Matthew D. , Rahbari Raheleh , Sebire Neil , Campbell Peter J. , Charnock-Jones D. Stephen , Smith Gordon C. S. , Behjati Sam 
Published: January 2021

ABSTRACTClinical investigations of human fetuses have revealed that placentas occasionally harbour chromosomal aberrations that are absent from the fetus1. The basis of this genetic segregation of the placenta, termed confined placental mosaicism, remains unknown. Here, we investigated the phylogeny of human placentas reconstructed from somatic mutations, using whole genome sequencing of 86 placental biopsies and of 106 microdissections. We found that every placental biopsy represented a clonal expansion that is genetically distinct. Biopsies exhibited a genomic landscape akin to childhood cancer, in terms of mutation burden and mutational imprints. Furthermore, unlike any other human normal tissue studied to date, placental genomes commonly harboured copy number changes. Reconstructing phylogenetic relationships between tissues from the same pregnancy, revealed that developmental bottlenecks confined placental tissues, by separating trophectodermal from inner cell mass-derived lineages. Of particular note were cases in which inner cell mass-derived and placental lineages fully segregated within a few cell divisions of the zygote. Such early embryonic bottlenecks may enable the normalisation of zygotic aneuploidy. We observed direct evidence for this in a case of mosaic trisomic rescue. Our findings reveal cancer-like mutagenesis in placental tissues and portray confined mosaicism as the normal outcome of placental development.
Modeling by artificial neural networks of silver carp (Hypophthalmichthys molitrixi) with sous vide processing on the effects of storage and processing temperatures on the microbiological status
Authors: Hosseini Seyed Vali , Pero Milad , Tahergorabi Reza , Kazemzadeh Shirin , Alemán Ricardo Santos , Fuentes Jhunior Abrahan Marcia , Fernández Ismael Montero , Sosa Lilian , Sanchez Xesus Feas 
Published: January 2021

AbstractTo evaluate and anticipate the microbial changes of silver carp (Hypophthalmichthys molitrixi) during cold storage (0, 5, 10, 15 & 21 day) at different sous vide processing temperatures (60, 65, 70, and 75 °C), changes in microbial load of Enterobacteriaceae, Lactic Acid bacteria (LAB), Pseudomonas, Psychrotrophs, and total viable count (TVC) were considered. A radial basis function neural network (RBFNN) model was established to predict the changes in the microbial content of silver carp. The critical temperature for inactivation of Enterobacteriaceae and lactic acid bacteria was 65 °C and for Pseudomonas and Psychrotrophs was 70 °C and the highest value (75 °C) was observed for the total viable count. In samples processed at 75 °C, the presence of Enterobacteriaceae, Pseudomonas and Psychrotrophs were not detectable up to 15 days of storage and lactic acid bacteria were not detectable even at the end of the storage period. The optimal ANN topology for modeling Enterobacteriaceae, Pseudomonas, and Psychrotroph contained 9 neurons in the hidden layer, but for TVC and LAB, it was 14 neurons.
Comprehensive analysis of male-free reproduction inMonomorium triviale(Formicidae: Myrmicinae)
Authors: Idogawa Naoto , Sasaki Tomonori , Tsuji Kazuki , Dobata Shigeto 
Published: January 2021

AbstractWe report comprehensive evidence for obligatory thelytokous parthenogenesis in an antMonomorium triviale. This species is characterized by distinct queen–worker dimorphism with strict reproductive division of labor: queens produce both workers and new queens without mating, whereas workers are completely sterile. We collected 333 nests of this species from 14 localities and three laboratory-reared populations in Japan. All wild queens dissected had no sperm in their spermathecae. Laboratory observation confirmed that virgin queens produced workers without mating. Furthermore, microsatellite genotyping showed identical heterozygous genotypes between mothers and their respective daughters, suggesting an extremely low probability of sexual reproduction. Microbial analysis detected no bacterial genera that are known to induce thelytokous parthenogenesis in Hymenoptera. Finally, the lack of variation in partial sequences of mitochondrial DNA among individuals sampled from across Japan suggests recent rapid spread or selective sweep.M. trivialewould be a promising model system of superorganism-like adaptation through comparative analysis with well-studied sexual congeners, including the pharaoh antM. pharaonis.
Comparison of mouse models reveals a molecular distinction between psychotic illness in PWS and schizophrenia
Authors: Zahova Simona K. , Humby Trevor , Davies Jennifer R. , Morgan Joanne E. , Isles Anthony R. 
Published: January 2021

ABSTRACTPrader-Willi Syndrome (PWS) is a neurodevelopmental disorder caused by mutations affecting paternal chromosome 15q11-q13, and characterized by hypotonia, hyperphagia, impaired cognition and behavioural problems. Psychotic illness is a challenging problem for individuals with PWS and has different rates of prevalence in distinct PWS genotypes. Previously, we demonstrated behavioural and cognitive endophenotypes of relevance to psychiatric illness in a mouse model for one of the associated PWS genotypes, namely PWS-IC, in which deletion of the imprinting centre leads to loss of paternal imprinted gene expression and over-expression ofUbe3a. Here we examine the broader gene expression changes that are specific to the psychiatric endophenotypes seen in this model. To do this we compared the brain transcriptomic profile of the PWS-IC mouse to the PWS-cr model that carries a deletion of the PWS minimal critical interval spanning the snoRNASnord116andIpw. Firstly, we examined the same behavioural and cognitive endophenotypes of relevance to psychiatric illness in the PWS-cr mice. Unlike the PWS-IC mice, PWS-cr exhibit no differences in locomotor activity, sensory-motor gating, and attention. RNA-seq analysis of neonatal whole brain tissue revealed a greater number of transcriptional changes between PWS-IC and wild-type littermates, than between PWS-cr and wild-type littermates. Moreover, the differentially expressed genes in the PWS-IC brain were enriched for GWAS variants of episodes of psychotic illness but, interestingly, not schizophrenia. These data illustrate the molecular pathways that may underpin psychotic illness in PWS and have implication for potential therapeutic interventions.
Normalization benchmark of ATAC-seq datasets shows the importance of accounting for GC-content effects
Authors: Van den Berge Koen , Chou Hsin-Jung , Roux de Bézieux Hector , Street Kelly , Risso Davide , Ngai John , Dudoit Sandrine 
Published: January 2021

AbstractModern assays have enabled high-throughput studies of epigenetic regulation of gene expression using DNA sequencing. In particular, the assay for transposase-accessible chromatin using sequencing (ATAC-seq) allows the study of chromatin configuration for an entire genome. Despite the gain in popularity of the assay, there have been limited studies investigating the analytical challenges related to ATAC-seq data, and most studies leverage tools developed for bulk transcriptome sequencing (RNA-seq). Here, we show that GC-content effects are omnipresent in ATAC-seq datasets. Since the GC-content effects are sample-specific, they can bias downstream analyses such as clustering and differential accessibility analysis. We introduce a normalization method based on smooth-quantile normalization within GC-content bins, and evaluate it together with eleven different normalization procedures on eight public ATAC-seq datasets. Our work clearly shows that accounting for GC-content effects in the normalization is crucial for common downstream ATAC-seq data analyses, leading to improved accuracy and interpretability of the results. Using two case studies, we show that exploratory data analysis is essential to guide the choice of an appropriate normalization method for a given dataset.
Towards Similarity-based Differential Diagnostics For Common Diseases
Authors: Slater Luke T , Karwath Andreas , Williams John A , Russell Sophie , Makepeace Silver , Carberry Alexander , Hoehndorf Robert , Gkoutos Georgios V 
Published: January 2021

AbstractOntology-based phenotype profiles have been utilised for the purpose of differential diagnosis of rare genetic diseases, and for decision support in specific disease domains. Particularly, semantic similarity facilitates diagnostic hypothesis generation through comparison with disease phenotype profiles. However, the approach has not been applied for differential diagnosis of common diseases, or generalised clinical diagnostics from uncurated text-derived phenotypes. In this work, we describe the development of an approach for deriving patient phenotype profiles from clinical narrative text, and apply this to text associated with MIMIC-III patient visits. We then explore the use of semantic similarity with those text-derived phenotypes to classify primary patient diagnosis, comparing the use of patient-patient similarity and patient-disease similarity using phenotype-disease profiles previously mined from literature. We also consider a combined approach, in which literature-derived phenotypes are extended with the content of text-derived phenotypes we mined from 500 patients. The results reveal a powerful approach, showing that in one setting, uncurated text phenotypes can be used for differential diagnosis of common diseases, making use of information both inside and outside the setting. While the methods themselves should be explored for further optimisation, they could be be applied to a variety of clinical tasks, such as differential diagnosis, cohort discovery, document and text classification, and outcome prediction.
Taurine suppresses liquid-liquid phase separation of lysozyme protein
Authors: Tsubotani Kanae , Maeyama Sayuri , Murakami Shigeru , Schaffer Stephen W , Ito Takashi 
Published: January 2021

AbstractTaurine is a compatible osmolyte that infers stability to proteins. Recent studies have revealed that liquid-liquid phase separation (LLPS) of proteins underlie the formation of membraneless organelles in cells. In the present study, we evaluated the role of taurine on LLPS of hen egg lysozyme. We demonstrated that taurine decreases the turbidity of the polyethylene glycol-induced crowding solution of lysozyme. We also demonstrated that taurine attenuates LLPS-dependent cloudiness of lysozyme solution with 0.5 or 1M NaCl at a critical temperature. Moreover, we observed that taurine inhibits LLPS formation of a heteroprotein mix solution of lysozyme and ovalbumin. These data indicate that taurine can modulate the formation of LLPS of proteins.
The Shape of Trees – Limits of Current Diversification Models
Authors: Schwery Orlando , O’Meara Brian C. 
Published: January 2021

AbstractTo investigate how biodiversity arose, the field of macroevolution largely relies on model-based approaches to estimate rates of diversification and what factors influence them. The number of available models is rising steadily, facilitating the modeling of an increasing number of possible diversification dynamics, and multiple hypotheses relating to what fueled or stifled lineage accumulation within groups of organisms. However, growing concerns about unchecked biases and limitations in the employed models suggest the need for rigorous validation of methods used to infer. Here, we address two points: the practical use of model adequacy testing, and what model adequacy can tell us about the overall state of diversification models. Using a large set of empirical phylogenies, and a new approach to test models using aspects of tree shape, we test how a set of staple models performs with regards to adequacy. Patterns of adequacy are described across trees and models and causes for inadequacy – particularly if all models are inadequate – are explored. The findings make clear that overall, only few empirical phylogenies cannot be described by at least one model. However, finding that the best fitting of a set of models might not necessarily be adequate makes clear that adequacy testing should become a step in the standard procedures for diversification studies.
Sequence signatures of two IGHV3-53/3-66 public clonotypes to SARS-CoV-2 receptor binding domain
Authors: Tan Timothy J.C. , Yuan Meng , Kuzelka Kaylee , Padron Gilberto C. , Beal Jacob R. , Chen Xin , Wang Yiquan , Rivera-Cardona Joel , Zhu Xueyong , Stadtmueller Beth M. , Brooke Christopher B. , Wilson Ian A. , Wu Nicholas C. 
Published: January 2021

AbstractSince the COVID-19 pandemic onset, the antibody response to SARS-CoV-2 has been extensively characterized. Antibodies to the receptor binding domain (RBD) on the spike protein are frequently encoded by IGHV3-53/3-66 with a short CDR H3. Germline-encoded sequence motifs in CDRs H1 and H2 play a major role, but whether any common motifs are present in CDR H3, which is often critical for binding specificity, have not been elucidated. Here, we identify two public clonotypes of IGHV3-53/3-66 RBD antibodies with a 9-residue CDR H3 that pair with different light chains. Distinct sequence motifs on CDR H3 are present in the two public clonotypes that appear to be related to differential light chain pairing. Additionally, we show that Y58F is a common somatic hypermutation that results in increased binding affinity of IGHV3-53/3-66 RBD antibodies with a short CDR H3. Overall, our results advance fundamental understanding of the antibody response to SARS-CoV-2.
E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil
Authors: Ferrareze Patrícia Aline Gröhs , Franceschi Vinícius Bonetti , de Menezes Mayer Amanda , Caldana Gabriel Dickin , Zimerman Ricardo Ariel , Thompson Claudia Elizabeth 
Published: January 2021

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people since its beginning in 2019. The propagation of new lineages and the discovery of key mechanisms adopted by the virus to overlap the immune system are central topics for the entire public health policies, research and disease management. Since the second semester of 2020, the mutation E484K has been progressively found in the Brazilian territory, composing different lineages over time. It brought multiple concerns related to the risk of reinfection and the effectiveness of new preventive and treatment strategies due to the possibility of escaping from neutralizing antibodies. To better characterize the current scenario we performed genomic and phylogenetic analyses of the E484K mutated genomes sequenced from Brazilian samples in 2020. From October, 2020, more than 40% of the sequenced genomes present the E484K mutation, which was identified in three different lineages (P1, P2 and B.1.1.33) in four Brazilian regions. We also evaluated the presence of E484K associated mutations and identified selective pressures acting on the spike protein, leading us to some insights about adaptive and purifying selection driving the virus evolution.
Low-Dose Ad26.COV2.S Protection Against SARS-CoV-2 Challenge in Rhesus Macaques
Authors: He Xuan , Chandrashekar Abishek , Zahn Roland , Wegmann Frank , Yu Jingyou , Mercado Noe B. , McMahan Katherine , Martinot Amanda J. , Piedra-Mora Cesar , Beecy Sidney , Ducat Sarah , Chamanza Ronnie , Huber Sietske Rosendahl , van der Fits Leslie , Borducchi Erica N. , Lifton Michelle , Liu Jinyan , Nampanya Felix , Patel Shivani , Peter Lauren , Tostanoski Lisa H. , Pessaint Laurent , Van Ry Alex , Finneyfrock Brad , Velasco Jason , Teow Elyse , Brown Renita , Cook Anthony , Andersen Hanne , Lewis Mark G. , Schuitemaker Hanneke , Barouch Dan H. 
Published: January 2021

AbstractWe previously reported that a single immunization with an adenovirus serotype 26 (Ad26) vector-based vaccine expressing an optimized SARS-CoV-2 spike (Ad26.COV2.S) protected rhesus macaques against SARS-CoV-2 challenge. In this study, we evaluated the immunogenicity and protective efficacy of reduced doses of Ad26.COV2.S. 30 rhesus macaques were immunized once with 1×1011, 5×1010, 1.125×1010, or 2×109vp Ad26.COV2.S or sham and were challenged with SARS-CoV-2 by the intranasal and intratracheal routes. Vaccine doses as low as 2×109vp provided robust protection in bronchoalveolar lavage, whereas doses of 1.125×1010vp were required for protection in nasal swabs. Activated memory B cells as well as binding and neutralizing antibody titers following vaccination correlated with protective efficacy. At suboptimal vaccine doses, viral breakthrough was observed but did not show evidence of virologic, immunologic, histopathologic, or clinical enhancement of disease compared with sham controls. These data demonstrate that a single immunization with a relatively low dose of Ad26.COV2.S effectively protected against SARS-CoV-2 challenge in rhesus macaques. Moreover, our findings show that a higher vaccine dose may be required for protection in the upper respiratory tract compared with the lower respiratory tract.