bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended Application of Genomic Selection to Screen Multi-Omics Data for Prognostic Signatures of Prostate Cancer
Authors: Li Ruidong , Wang Shibo , Cui Yanru , Qu Han , Chater John M. , Zhang Le , Wei Julong , Wang Meiyue , Xu Yang , Yu Lei , Lu Jianming , Feng Yuanfa , Zhou Rui , Huang Yuhan , Ma Renyuan , Zhu Jianguo , Zhong Weide , Jia Zhenyu 
Published: June 2020

AbstractPrognostic tests using expression profiles of several dozen genes help provide treatment choices for prostate cancer (PCa). However, these tests require improvement to meet the clinical need for resolving overtreatment which continues to be a pervasive problem in PCa management. Genomic selection (GS) methodology, which utilizes whole-genome markers to predict agronomic traits, was adopted in this study for PCa prognosis. We leveraged The Cancer Genome Atlas (TCGA) database to evaluate the prediction performance of six GS methods and seven omics data combinations, which showed that the Best Linear Unbiased Prediction (BLUP) model outperformed the other methods regarding predictability and computational efficiency. Leveraging the BLUP-HAT method, an accelerated version of BLUP, we demonstrated that using expression data of a large number of disease-relevant genes and with an integration of other omics data (i.e., miRNAs) significantly increased outcome predictability when compared with panels consisting of small numbers of genes. Finally, we developed a novel stepwise forward selection BLUP-HAT method to facilitate searching multi-omics data for predictor variables with prognostic potential. The new method was applied to the TCGA data to derive mRNA and miRNA expression signatures for predicting relapse-free survival of PCa, which were validated in six independent cohorts. This is a transdisciplinary adoption of the highly efficient BLUP-HAT method and its derived algorithms to analyze multi-omics data for PCa prognosis. The results demonstrated the efficacy and robustness of the new methodology in developing prognostic models in PCa, suggesting a potential utility in managing other types of cancer.
Diploid chromosome-scale assembly of theMuscadinia rotundifoliagenome supports chromosome fusion and disease resistance gene expansion duringVitisandMuscadiniadivergence
Authors: Cochetel Noé , Minio Andrea , Massonnet Mélanie , Vondras Amanda M. , Figueroa-Balderas Rosa , Cantu Dario 
Published: June 2020

ABSTRACTMuscadinia rotundifolia, the muscadine grape, has been cultivated for centuries in the southeastern United States.M. rotundifoliais resistant to many of the pathogens that detrimentally affectVitis vinifera, the grape species commonly used for winemaking. For this reason,M. rotundifoliais a valuable genetic resource for breeding. Single-molecule real-time reads were combined with optical maps to reconstruct the two haplotypes of each of the 20M. rotundifoliacv. Trayshed chromosomes. The completeness and accuracy of the assembly were confirmed using a high-density linkage map ofM. rotundifolia.Protein-coding genes were annotated using an integrated and comprehensive approach. This included using Full-length cDNA sequencing (Iso-Seq) to improve gene structure and hypothetical spliced variant predictions. Our data strongly support thatMuscadiniachromosomes 7 and 20 are fused inVitisand pinpoint the location of the fusion in Cabernet Sauvignon and PN40024 chromosome 7. Disease-related gene numbers in Trayshed and Cabernet Sauvignon were similar, but their clustering locations were different. A dramatic expansion of the Toll/Interleukin-1 Receptor-like Nucleotide-Binding Site Leucine-Rich Repeat (TIR-NBS-LRR) class was detected on Trayshed chromosome 12 at theResistance to Uncinula necator 1(RUN1)/Resistance to Plasmopara viticola 1(RPV1) locus, which confers strong dominant resistance to powdery and downy mildews. A genome browser for Trayshed, its annotation, and an associated Blast tool are available atwww.grapegenomics.com.
A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-Pertussis toxoid antibodies
Authors: Richardson Eve , Galson Jacob D. , Kellam Paul , Kelly Dominic F. , Smith Sarah E. , Palser Anne , Watson Simon , Deane Charlotte M. 
Published: June 2020

AbstractDue to their shared genetic history, antibodies from the same clonotype often bind to the same epitope. This knowledge is used in immune repertoire mining, where known binders are used to search bulk sequencing repertoires to identify new binders. However current computational methods cannot identify epitope convergence between antibodies from different clonotypes, limiting the sequence diversity of antigen-specific antibodies which can be identified. We describe how the antibody binding site, the paratope, can be used to cluster antibodies with common antigen reactivity from different clonotypes. Our method, paratyping, uses the predicted paratope to identify these novel cross clonotype matches. We experimentally validated our predictions on a Pertussis toxoid dataset. Our results show that even the simplest abstraction of the antibody binding site, using only the length of the loops involved and predicted binding residues, is sufficient to group antigen-specific antibodies and provide additional information to conventional clonotype analysis.
Optogenetic currents in myofibroblasts acutely alter electrophysiology and conduction of co-cultured cardiomyocytes
Authors: Kostecki Geran , Shi Yu , Chen Christopher , Reich Daniel H. , Entcheva Emilia , Tung Leslie 
Published: June 2020

AbstractInteractions between cardiac myofibroblasts and myocytes may slow conduction after cardiac injury, increasing the chance of life-threatening arrhythmia. While co-culture studies have shown that myofibroblasts can affect cardiomyocyte electrophysiologyin vitro, the mechanism(s) remain debatable. In this study, primary neonatal rat cardiac myofibroblasts were transduced with the light-activated ion channel Channelrhodopsin-2, which allowed acute and selective modulation of myofibroblast currents in co-cultures with cardiomyocytes. Optical mapping revealed that myofibroblast-specific optogenetically induced inward currents decreased conduction velocity in the co-cultures by 27±6% (baseline = 17.7±5.3 cm/s), and shortened the cardiac action potential duration by 14±7% (baseline = 161±11 ms) when 0.017 mW/mm2light was applied. When light irradiance was increased to 0.057 mW/mm2, the myofibroblast currents led to spontaneous beating in 6/7 co-cultures. Experiments showed that optogenetic perturbation did not lead to changes in myofibroblast strain and force generation, suggesting purely electrical effects in this model.In silicomodeling of optogenetically modified myofibroblast-cardiomyocyte co-cultures largely reproduced these results and enabled a comprehensive study of relevant parameters. These results clearly demonstrate that myofibroblasts are sufficiently electrically connected to cardiomyocytes to effectively alter macroscopic electrophysiological properties in this model of cardiac tissue.
The Cryo-EM structure of AAV2 Rep68 in complex with ssDNA reveals a malleable AAA+machine that can switch between oligomeric states
Authors: Santosh Vishaka , Musayev Faik , Jaiswal Rahul , Zárate-Pérez Francisco , Vandewinkel Bram , Dierckx Caroline , Endicott Molly , Sharifi Kamyar , Dryden Kelly , Henckaerts Els , Escalante Carlos R. 
Published: June 2020

AbstractThe adeno-associated virus (AAV) Rep proteins use a unique AAA+domain to catalyze DNA replication, transcription regulation, and genome packaging. Also, they mediate site-specific integration during a latent phase. To understand the mechanisms underlying AAV Rep function, we investigated the cryo-EM and X-ray structures of Rep68-ssDNA complexes. Surprisingly, Rep68 generates hybrid ring structures where the Origin-Binding-Domain (OBD) forms octameric rings while the helicase domain (HD) forms heptamers. Moreover, the binding to ATPγS promotes a large conformational change in the entire AAA+domain that leads the HD to form both heptamer and hexamers. The HD oligomerization is driven by an interdomain linker region that acts as a latch to ‘catch’ the neighboring HD subunit and is flexible enough to permit the formation of different stoichiometric ring structures. Overall, our studies show the structural basis of AAV Rep’s structural flexibility required to fulfill its multifunctional role during the AAV life cycle.
Glycopeptidomics Analysis of a Cell Line Model Revealing Pathogenesis and Potential Marker Molecules for the Early Diagnosis of Gastric MALT Lymphoma
Authors: Xiao Di , Meng Le , Xu Yanli , Zhang Huifang , Meng Fanliang , He Lihua , Zhang Jianzhong 
Published: June 2020

ABSTRACTBackgroundGastric mucosa-associated lymphoma (GML) is a mature B cell tumor related toHelicobacter pylori(H.pylori) infection. The clinical manifestations of GML are not specific, so GML commonly escapes diagnosis or is misdiagnosed, leading to excessive treatment. The pathogenesis ofH.pylori-induced GML is not well understood and there are no molecular markers for early GML diagnosis.MethodsGlycopeptidomics analyses of host cell lines (a BCG823 cell line, C823) and C823 cells infected byH. pyloriisolated from patients with GML (GMALT823), gastritis (GAT823), gastric ulcer (GAU823) and gastric cancer (GAC823) were carried out to clarify the host reaction mechanism against GML and identify potential molecular criteria for the early diagnosis of GML.FindingsThirty-three samples were analyzed and approximately 2000 proteins, 200 glycoproteins and 500 glycopeptides were detected in each sample. O-glycans were the dominant glycoforms in GMALT823 cells only. Four specific glycoforms in GMALT823 cells and 2 specific glycoforms in C823 and GMALT823 cells were identified. Eight specific glycopeptides of from 7 glycoproteins were found in GMALT823 cells; of these glycopeptides, 6 and 3 specific glycopeptides had high affinity for T cell epitopes and have conformational B cell epitopes, respectively.InterpretationThe relationship between the predominant glycoforms of host cells and the development of host disease was determined, and the glycoproteins, glycosylation sites and glycoforms might be closely related to the formation of GML, which provides new insight into the pathogenic mechanisms ofH. pyloriinfection and suggests molecular indicators for the early diagnosis of GML.
PENGUINN: Precise Exploration of Nuclear G-quadruplexes Using Interpretable Neural Networks
Authors: Klimentova Eva , Polacek Jakub , Simecek Petr , Alexiou Panagiotis 
Published: June 2020

AbstractG-quadruplexes (G4s) are a class of stable structural nucleic acid motifs that are known to play a role in a wide spectrum of genomic functions, such as DNA replication and transcription. The classical understanding of G4 structure points to four variable length guanine strands joined by variable length stretches of other nucleotides. Experiments using G4 immunoprecipitation and sequencing experiments have produced a high number of highly probable G4 forming genomic sequences. The expense and technical difficulty of experimental techniques highlights the need for computational approaches of G4 identification. Here, we present PENGUINN, a machine learning method based on Convolutional Neural Networks, that learns the characteristics of G4 sequences and accurately predicts G4s outperforming the state-of-the-art. We provide both a standalone implementation of the trained model, and a web application that can be used to evaluate sequences for their G4 potential.
Integer topological defects organize stresses driving tissue morphogenesis
Authors: Guillamat Pau , Blanch-Mercader Carles , Kruse Karsten , Roux Aurélien 
Published: June 2020

AbstractTissues acquire their function and shape via differentiation and morphogenesis. Both processes are driven by coordinating cellular forces and shapes at the tissue scale, but general principles governing this interplay remain to be discovered. Here, we report that self-organization of myoblasts around integer topological defects, namely spirals and asters, triggers localized differentiation and, when differentiation is inhibited, drives the growth of cylindrical multicellular protrusions. Both localized differentiation and growth require specific stress patterns. By analyzing the experimental velocity and orientation profiles through active gel theory, we show that integer topological defects can concentrate compressive stresses, which we measure by using deformable pillars. Altogether, we envision topological defects as mechanical organizational centers that control differentiation and morphogenesis to establish tissue architecture.
Ecological Differentiation Among Globally Distributed Lineages of the Rice Blast Fungus Pyricularia oryzae
Authors: Thierry Maud , Charriat Florian , Milazzo Joëlle , Adreit Henri , Ravel Sébastien , Cros-Arteil Sandrine , Borron Sonia , Sella Violaine , Kroj Thomas , Ioos Renaud , Fournier Elisabeth , Tharreau Didier , Gladieux Pierre 
Published: June 2020

ABSTRACTMany invasive fungal species coexist as multiple lineages on the same host, but the factors underlying the origin and maintenance of population structure remain largely unknown. Here, we analyzed genetic and phenotypic diversity in isolates of the rice blast fungus (Pyricularia oryzae) covering a broad geographical range. We showed that the four lineages of P. oryzae were found in areas with different prevailing environmental conditions and types of rice grown, indicating niche separation. Pathogenicity tests revealed that specialization to rice subspecies contributed to niche separation between lineages, and differences in repertoires of putative virulence effectors were consistent with differences in host range. Experimental crosses revealed that female sterility and early post-mating genetic incompatibilities acted as strong barriers to gene flow between these lineages. Our results demonstrate that the spread of a pathogen across heterogeneous habitats and divergent populations of a crop species can lead to niche separation and reproductive isolation between distinct invasive lineages.
Neuralized regulates a travelling wave of Epithelium-to-Neural Stem Cell morphogenesis inDrosophila
Authors: Shard Chloé , Luna-Escalante Juan , Schweisguth François 
Published: June 2020

AbstractMany tissues are produced during development by specialized progenitor cells emanating from epithelia via an Epithelial-to-Mesenchymal Transition (EMT). Most studies have so far focused on cases involving single or isolated groups of cells. Here we describe an EMT-like process that requires tissue level coordination. This EMT-like process occurs along a continuous front in theDrosophilaoptic lobe neuroepithelium to produce neural stem cells (NSCs). We find that emerging NSCs remain epithelial and apically constrict before dividing asymmetrically to produce neurons. Apical constriction is associated with contractile myosin pulses and requires the E3 ubiquitin ligase Neuralized and RhoGEF3. Neuralized down-regulates the apical protein Crumbs via its interaction with Stardust. Disrupting the regulation of Crumbs by Neuralized led to defects in apical constriction and junctional myosin accumulation, and to imprecision in the integration of emerging NSCs into the transition front. Neuralized therefore appears to mechanically couple NSC fate acquisition with cell-cell rearrangement to promote smooth progression of the differentiation front.
A validated and interpretable predictive model of cruzain inhibitors
Authors: Rosas-Jimenez Jose G. , Garcia-Revilla Marco A. , Madariaga-Mazon Abraham , Martinez-Mayorga Karina 
Published: June 2020

AbstractChagas disease affects 8–11 million people worldwide, most of them living in Latin America. Moreover, migratory phenomenon have spread the infection beyond endemic areas. Efforts for the development of new pharmacological therapies are paramount, as the pharmacological profile of the two marketed drugs currently available, nifurtimox and benznidazole, needs to be improved. Cruzain, a parasitic cysteine protease, is one of the most attractive biological targets due to its roles in parasite survival and immune evasion. In this work, we generated Quantitative Structure-Activity Relationship linear models for the prediction of pIC50values of cruzain inhibitors. The statistical parameters for internal and external validation indicate high predictability with a cross-validated correlation coefficient ofand an external correlation coefficient of. The applicability domain is quantitatively defined, according to QSAR good practices, using the leverage method. A qualitative interpretation of the model is provided based on protein-ligand interactions obtained from docking studies and structural information codified in the molecular descriptors relevant to the QSAR model. The model described in this work will be valuable for the discovery of novel cruzain inhibitors.Author summaryChagas disease is a major health problem in Latin America. The disease involves a long-lasting silent phase that usually culminates in serious or fatal heart damage. Despite its prevalence, there are only two antichagas approved drugs available. Despite these drugs have been in the market for more than 50 years, significant undesirable side effects and modest effectiveness in the chronic phase are prevalent. The need of new drugs to treat this disease is evident. Cruzain is a vital protein for the survival ofTrypanosoma cruzi,the parasite causative of Chagas disease. Inhibition of this species-specific protein has been associated with improvements in pharmacological effects in animal models. Thus, blocking the activity of cruzain is an attractive approach for the development of antichagas agents. In this work, we present a validated mathematical model capable of predicting the cruzain inhibition value of a molecule from its chemical structure. This model can contribute to the identification of potential pharmacological alternatives against Chagas disease.
Nationwide survey on the barriers to converting turfgrass lawns to pollinator-friendly native wildflowers
Authors: Turley Nash E. , Hogan Joshua , Diehl Gloria J. , Stack Aaron C. , Sharanowski Barbara J. 
Published: June 2020

AbstractThe abundance and diversity of insect pollinators around the world is declining and habitat loss is a leading cause. Turfgrass lawns cover a vast area in North America and provide a great opportunity for habitat restoration to native wildflowers by the general public. Efforts to encourage the public to replace lawns with wildflowers could be improved by a better understanding of the thoughts and opinions of the public about lawns. We conducted a nationwide online survey to understand what barriers are most important in preventing people from converting a 6 x 6 ft portion of turfgrass lawn to native wildflowers. We also collected data on a variety of demographic factors to see if those influence survey responses. Over 3200 people took survey across the US. We found that ‘Maintenance time’ and ‘Not knowing what to do’ were the most important barriers to creating wildflower habitat. Age was the most important demographic factor impacting results with young people significantly more likely to select multiple barriers in the survey. For example, people aged 18-34 were 4.3 times more likely to indicate ‘Maintenance cost’ would prevent them from creating a wildflower plot than those age 65 or older. Those who had already created a wildflower plot, or those who were members in a native plant or pollinator organization were less likely to select barriers across the board, except for external barriers related to homeowners associations, neighbors, and local governments. This shows that these are persistent concerns even for those that are otherwise keen to create wildflower habitat. Our results suggest that outreach promoting pollinator-friendly native plant gardens should focus on clear and simple methods, small plots that will not take too much time and less likely to provoke neighbors or authority figures.
Sleep and circadian phenotype in people without cone-mediated vision
Authors: Spitschan Manuel , Garbazza Corrado , Kohl Susanne , Cajochen Christian 
Published: June 2020

AbstractBackgroundLight exposure entrains the circadian clock through the intrinsically photosensitive retinal ganglion cells, which sense light in addition to the cones and rods. In congenital achromatopsia (ACHM; prevalence 1:30-50,000), the cone system is non-functional, resulting in severe light avoidance and photophobia at daytime light levels. How this condition affects circadian and neuroendocrine responses to light is not known.MethodsIn genetically confirmed ACHM patients (n=7; age 30-72 years; 6 women, 1 male), we examined survey-assessed sleep/circadian phenotype (PSQI, ESS, MEQ, MCTQ), self-reported visual function (NEI-VFQ-25), sensitivity to light (VLSQ-8) and use of spectral filters that modify chronic light exposure. In all but one patient, we measured rest-activity cycles using actigraphy over 3 weeks and measured the melatonin phase angle of entrainment using the dim-light melatonin onset (DLMO).ResultsACHM patients experience a severely attenuated light-dark cycle due to severe light sensitivity and habitual use of filters to reduce retinal illumination. In aggregate, both MEQ and MCTQ indicated a tendency to late chronotype. We found regular rest-activity patterns in all patients and normal phase angles of entrainment in participants with a measurable DLMO.ConclusionsOur results reveal that a functional cone system and exposure to daytime light intensities are not necessary for regular behavioural and hormonal entrainment, even when survey-assessed sleep and circadian phenotype indicated a tendency for a late chronotype and sleep problems in our ACHM cohort. Our results can be explained by an adaptation mechanism in circadian photoreception which adjusts to the range of habitual light exposures.
Sequence diversity and evolution of an iflavirus family associated with ticks
Authors: Daveu Romain , Hervet Caroline , Sigrist Louane , Sassera Davide , Jex Aaron , Labadie Karine , Aury Jean-Marc , Plantard Olivier , Rispe Claude 
Published: June 2020

AbstractWe studied a family of iflaviruses, a group of RNA viruses frequently found in arthropods, focusing on viruses associated with ticks. Our aim was to bring insight on the evolutionary dynamics of this group of viruses, which may interact with the biology of ticks. We explored systematicallyde novoRNA-Seq assemblies available for species of ticks which allowed to identify nine new genomes of iflaviruses. The phylogeny of virus sequences was not congruent with that of the tick hosts, suggesting recurrent host changes across tick genera along evolution. We identified five different variants with a complete or near-complete genome inIxodes ricinus.These sequences were closely related, which allowed a fine-scale estimation of patterns of substitutions: we detected a strong excess of synonymous mutations suggesting evolution under strong positive selection. ISIV, a sequence found in the ISE6 cell line ofIxodes scapularis,was unexpectedly nearidentical withI. ricinusvariants, suggesting a contamination of this cell line byI. ricinusmaterial. Overall, our work constitutes a step in the understanding of the interactions between this family of viruses and ticks.