bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galaxy-SynBioCAD: Synthetic Biology Design Automation tools in Galaxy workflows
Authors: du Lac Melchior , Duigou Thomas , Hérisson Joan , Carbonell Pablo , Swainston Neil , Zulkower Valentin , Shah Forum , Faure Léon , Mahdy Mostafa , Soudier Paul , Faulon Jean-Loup 
Published: June 2020

AbstractMany computer-aided design tools are available for synthetic biology and metabolic engineering. Yet, these tools can be difficult to apprehend, sometimes requiring a level of expertise that limits their use by a wider community. Furthermore, some of the tools, although complementary, rely on different input and output formats and cannot communicate with one another. Scientific workflows address these shortcomings while offering a novel design strategy. Among the workflow systems available, Galaxy is a web-based platform for performing findable and accessible data analyses for all scientists regardless of their informatics expertise, along with interoperable and reproducible computations regardless of the particular platform that is being used.Here, we introduce the Galaxy-SynBioCADaportal, the first Galaxy toolshed for synthetic biology and metabolic engineering. It allows one to easily create workflows or use those already developed by the community. The portal is a growing community effort where developers can add new tools and users can evaluate the tools performing design for their specific projects. The tools and workflows currently shared on the Galaxy-SynBioCAD portal cover an end-to-end metabolic pathway design process from the selection of strain and target to the calculation of DNA parts to be assembled to build libraries of strains to be engineered to produce the target.Standard formats are used throughout to enforce the compatibility of the tools. These include SBML for strain and pathway and SBOL for genetic layouts. The portal has been benchmarked on 81 literature pathways, overall, we find we have a 65% (and 88%) success rate in retrieving the literature pathways among the top 10 (50) pathways predicted and generated by the workflows.
Stiffening of prostate cancer cells driven by actin filaments – microtubules crosstalk confers resistance to microtubule-targeting drugs
Authors: Kubiak Andrzej , Chighizola Matteo , Schulte Carsten , Bryniarska Natalia , Wesołowska Julita , Pudełek Maciej , Ryszawy Damian , Basta-Kaim Agnieszka , Laidler Piotr , Podesta Alessandro , Lekka Malgorzata 
Published: June 2020

AbstractThe crucial role of microtubules in the mitotic-related segregation of chromosomes makes them an excellent target for anticancer microtubule targeting drugs (MTDs) such as vinflunine, colchicine, and docetaxel. MTDs affect mitosis by directly perturbing the structural organization of microtubules. By a direct assessment of the biomechanical properties of prostate cancer cells exposed to different MTDs using atomic force microscopy, we show that cell stiffening is a candidate mechanism through which cancer cells preserve the original phenotype in response to the application of MTDs. While changes in cellular rigidity are typically mainly attributed to remodeling of the actin filaments in the cytoskeleton, here we provide evidence that cell stiffening can be driven by a crosstalk between actin filaments and microtubules in drug-treated cells. Our findings improve the interpretation of biomechanical data obtained for living cells in studies of various physiological and pathological processes.
Hybridization history and repetitive element content in the genome of a homoploid hybrid,Yucca gloriosa(Asparagaceae)
Authors: Heyduk Karolina , McAssey Edward V. , Grimwood Jane , Shu Shengqiang , Schmutz Jeremy , McKain Michael R. , Leebens-Mack Jim 
Published: June 2020

AbstractHybridization in plants results in phenotypic and genotypic perturbations that can have dramatic effects on hybrid physiology, ecology, and overall fitness. Hybridization can also perturb epigenetic control of transposable elements, resulting in their proliferation. Understanding the mechanisms that maintain genomic integrity after hybridization is often confounded by changes in ploidy that occur in hybrid plant species. Homoploid hybrid species, which have no change in chromosome number relative to their parents, offer an opportunity to study the genomic consequences of hybridization in the absence of change in ploidy.Yucca gloriosa(Asparagaceae) is a young homoploid hybrid species, resulting from a cross betweenYucca aloifoliaandYucca filamentosa. Previous analyses of ~11kb of the chloroplast genome and nuclear-encoded microsatellites implicated a singleY. aloifoliagenotype as the maternal parent ofY. gloriosa.Using whole genome resequencing, we assembled chloroplast genomes from multiple accessions of all three species to re-assess the hybrid origins ofY. gloriosa.We further used re-sequencing data to annotate transposon abundance in the three species and mRNA-seq to analyze transcription of transposons. The chloroplast phylogeny and haplotype analysis suggest multiple hybridization events contributing to the origin ofY. gloriosa,with both parental species acting as the maternal donor. Transposon abundance at the superfamily level was significantly different between the three species; the hybrid was frequently intermediate to the parental species in TE superfamily abundance or appeared more similar to one or the other parent. In only one case –CopiaLTR transposons – didY. gloriosahave a significantly higher abundance relative to either parent. Expression patterns across the three species showed little increased transcriptional activity of transposons, suggesting that either no transposon release occurred inY. gloriosaupon hybridization, or that any transposons that were activated via hybridization were rapidly silenced. Further work will assess the degree to which transposon abundance and location has affected the epigenomic landscape, gene expression, and ecophysiology inY. gloriosa.
Human prefoldin modulates co-transcriptional pre-mRNA splicing
Authors: Payán-Bravo Laura , Fontalva Sara , Peñate Xenia , Cases Ildefonso , Guerrero-Martínez José Antonio , Pareja-Sánchez Yerma , Odriozola-Gil Yosu , Lara Esther , Jimeno-González Silvia , Suñé Carles , Muñoz-Centeno Mari Cruz , Reyes José C. , Chávez Sebastián 
Published: June 2020

ABSTRACTPrefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing.
Interdependence of CTL and NK cell cytotoxicity against melanoma cells
Authors: Friedmann Kim S. , Knörck Arne , Cappello Sabrina , Hoxha Cora , Schwär Gertrud , Iden Sandra , Bogeski Ivan , Kummerow Carsten , Schwarz Eva C. , Hoth Markus 
Published: June 2020

AbstractCTL and NK cells recognize and eliminate cancer cells. However, immune evasion, down regulation of immune function by the tumor microenvironment, or resistance of cancer cells are a major problem. While CTL and NK cells are both important to eliminate cancer, most studies address them individually. In a new experimental human model, we analysed combined primary human CTL and NK cell cytotoxicity against the melanoma cell line SK-Mel-5. At high effector-to-target ratios, MART-1-specific CTL or NK cells eliminated SK-Mel-5 cells within 24 hours indicating that SK-Mel-5 cells are initially not resistant. However, at lower effector-to-target ratios, which resemble conditions of the immune contexture in human cancer, a significant number of SK-Mel-5 cells survived. Whereas CTL pre-exposure induced resistance in surviving SK-Mel-5 cells to subsequent CTL or NK cell cytotoxicity, NK cell pre-exposure induced resistance in surviving SK-Mel-5 cells to NK cells but not to MART-1 specific CTL. In contrast, there was even a slight enhancement of CTL cytotoxicity against SK-Mel-5 cells following NK cell pre-exposure. In all other combinations, resistance to subsequent cytotoxicity was higher, if melanoma cells were pre-exposed to larger numbers of CTL or NK cells. Increases in human leukocyte antigen class I expression correlated with resistance to NK cells, while reduction in MART-1 antigen expression correlated with reduced CTL cytotoxicity. CTL cytotoxicity was rescued beyond control levels by exogenous MART-1 antigen. This study quantifies the interdependence of CTL and NK cell cytotoxicity and may guide strategies for efficient CTL-NK cell anti-melanoma therapies.Key points summaryCytotoxic T lymphocytes (CTL) and natural killer (NK) cells eliminate cancer cells. CTL and NK work in parallel, but most studies address them individually.In a new human experimental model, antigen-specific CTL and NK cell cytotoxicity interdependence against melanoma is shown.Whereas high numbers of antigen-specific CTL and NK cells eliminate all melanoma cells, lower, more physiological numbers induce resistance, in case secondary CTL or NK cell exposure follow initial CTL cell exposure or if secondary NK cell exposure follows initial NK cell exposure; only if secondary CTL exposure follows initial NK cell exposure no resistance of melanoma but even a slight enhancement of cytotoxicity was observed.Alterations in HLA-I expression correlated with resistance to NK cells, while reduction in antigen expression correlated with reduced CTL cytotoxicity. CTL cytotoxicity was rescued beyond control levels by exogenous antigen.The results should help to better understand and optimize immune therapies against cancer.Graphical abstract
Human library of cardiac promoters and enhancers
Authors: Deviatiiarov Ruslan M. , Gams Anna , Syunyaev Roman , Tatarinova Tatiana V. , Gusev Oleg , Efimov Igor R. 
Published: June 2020

AbstractGenome regulatory elements play a critical role during cardiac development and maintenance of normal physiological homeostasis, and genome-wide association studies identified a large number of SNPs associated with cardiovascular diseases localized in intergenic zones. We used cap analysis of gene expression (CAGE) to identify transcription start sites (TSS) with one nucleotide resolution that effectively maps genome regulatory elements in a representative collection of human heart tissues. Here we present a comprehensive and fully annotated CAGE atlas of human promoters and enhancers from four chambers of the non-diseased human donor hearts, including both atria and ventricles. We have identified 10,528 novel regulatory elements, where 2,750 are classified as TSS and 4,258 novel enhancers, which were validated with ChIP-seq libraries and motif enrichment analysis. We found that heart-region specific expression patterns are primarily based on the alternative promoter and specific enhancer activity. Our study significantly increased evidence of the association of regulatory elements-located variants with heart morphology and pathologies. The precise location of cardiac disease-related SNPs within the regulatory regions and their correlation with a specific cell type offers a new understanding of genetic heart diseases.
Calcium ion chelation preserves platelet function during cold storage
Authors: Xiang Binggang , Zhang Guoying , Zhang Yan , Wu Congqing , Joshi Smita , Morris Andrew J. , Ware Jerry , Smyth Susan S. , Whiteheart Sidney W. , Li Zhenyu 
Published: June 2020

AbstractObjectivePlatelet transfusion is a life-saving therapy to prevent or treat bleeding in patients with thrombocytopenia or platelet dysfunction. However, for more than six decades, safe and effective strategies for platelet storage have been an impediment to widespread use of platelet transfusion. Refrigerated platelets are cleared rapidly from circulation, precluding cold storage of platelets for transfusion. Consequently, platelets are stored at room temperature (RT) with an upper limit of 5 days due to risks of bacterial contamination and loss of platelet function. This practice severely limits platelet availability for transfusion. This study is to identify the mechanism of platelet clearance after cold storage and develop a method for platelet cold storage.Approach and ResultsWe found that rapid clearance of cold-stored platelets was largely due to integrin activation and apoptosis. Deficiency of integrin β3 or caspase-3 prolonged cold-stored platelets in circulation. Pre-treatment of platelets with EGTA, a cell impermeable calcium ion chelator, reversely inhibited cold storage-induced platelet activation and consequently prolonged circulation of cold-stored platelets. Moreover, transfusion of EGTA-treated, cold-stored platelets, but not RT-stored platelets, into the mice deficient in glycoprotein Ibα significantly shortened tail-bleeding times and diminished blood loss.ConclusionIntegrin activation and apoptosis is the underlying mechanism of rapid clearance of platelets after cold storage. Addition of a cell impermeable calcium ion chelator to platelet products is potentially a simple and effective method to enable cold storage of platelets for transfusion.
De novogenome assembly and transcriptome analysis for the drought and salt resistantSolanum sitiens
Authors: Molitor C. , Kurowski T.J. , Fidalgo de Almeida P.M. , Eerolla P. , Spindlow D.J. , Kashyap S.P. , Singh B. , Prasanna H.C. , Thompson A.J. , Mohareb F.R. 
Published: June 2020

AbstractSolanum sitiensis a self-incompatible wild relative of tomato, characterised by salt and drought resistance traits, with the potential to contribute to crop improvement in cultivated tomato. This species has a distinct morphology, classification and ecotype compared to other stress resistant wild tomato relatives such asS. pennelliiandS. chilense. Therefore, the availability of a high-quality reference genome forS. sitienswill facilitate the genetic and molecular understanding of salt and drought resistance. Here, we present ade novogenome and transcriptome assembly forS. sitiens(Accession LA1974). A hybrid assembly strategy was followed using Illumina short reads (∼159X coverage) and PacBio long reads (∼44X coverage), generating a total of ∼262 Gbp of DNA sequence; in addition, ∼2,670 Gbp of BioNano data was obtained. A reference genome of 1,245 Mbp, arranged in 1,481 scaffolds with a N50 of 1,826 Mbp was generated. Genome completeness was estimated at 95% using the Benchmarking Universal Single-Copy Orthologs (BUSCO) and the K-mer Analysis Tool (KAT); this is within the range of current high-quality reference genomes for other tomato wild relatives. Additionally, we identified three large inversions compared toS. lycopersicum, containing several drought resistance related genes, such asbeta-amylase 1andYUCCA7.In addition, ∼63 Gbp of RNA-Seq were generated to support the prediction of 31,164 genes from the assembly, and perform ade novotranscriptome. Some of the protein clusters unique toS. sitienswere associated with genes involved in drought and salt resistance, includingGLO1andFQR1.This first reference genome forS. sitienswill provide a valuable resource to progress QTL studies to the gene level, and will assist molecular breeding to improve crop production in water-limited environments.
Synthetic data generation with probabilistic Bayesian Networks
Authors: Gogoshin Grigoriy , Branciamore Sergio , Rodin Andrei S. 
Published: June 2020

AbstractBayesian Network (BN) modeling is a prominent and increasingly popular computational systems biology method. It aims to construct probabilistic networks from the large heterogeneous biological datasets that reflect the underlying networks of biological relationships. Currently, a variety of strategies exist for evaluating BN methodology performance, ranging from utilizing artificial benchmark datasets and models, to specialized biological benchmark datasets, to simulation studies that generate synthetic data from predefined network models. The latter is arguably the most comprehensive approach; however, existing implementations are typically limited by their reliance on the SEM (structural equation modeling) framework, which includes many explicit and implicit assumptions that may be unrealistic in a typical biological data analysis scenario. In this study, we develop an alternative, purely probabilistic, simulation framework that more appropriately fits with real biological data and biological network models. In conjunction, we also expand on our current understanding of the theoretical notions of causality and dependence / conditional independence in BNs and the Markov Blankets within.
Dose-dependent enhancement of motion direction discrimination with transcranial magnetic stimulation of visual cortex
Authors: Gamboa Arana Olga Lucia , Palmer Hannah , Dannhauer Moritz , Hile Connor , Liu Sicong , Hamdan Rena , Brito Alexandra , Cabeza Roberto , Davis Simon W. , Peterchev Angel V. , Sommer Marc A. , Appelbaum Lawrence G. 
Published: June 2020

AbstractDespite the widespread use of transcranial magnetic stimulation (TMS) in research and clinical care, the underlying mechanisms-of-actions that mediate modulatory effects remain poorly understood. To fill this gap, we studied dose–response functions of TMS for modulation of visual processing. Our approach combined electroencephalography (EEG) with application of single pulse TMS to visual cortex as participants performed a motion perception task. During participants’ first visit, motion coherence thresholds, 64-channel visual evoked potentials (VEPs), and TMS resting motor thresholds (RMT) were measured. In second and third visits, single pulse TMS was delivered 30 ms before the onset of motion or at the onset latency of the N2 VEP component derived from the first session. TMS was delivered at 0%, 80%, 100%, or 120% of RMT over the site of N2 peak activity, or at 120% over vertex. Behavioral results demonstrated a significant main effect of TMS timing on accuracy, with better performance when TMS was applied at N2-Onset timing versus Pre-Onset, as well as a significant interaction, indicating that 80% intensity produced higher accuracy than other conditions. TMS effects on VEPs showed reduced amplitudes in the 80% Pre-Onset condition, an increase for the 120% N2-Onset condition, and monotonic amplitude scaling with stimulation intensity. The N2 component was not affected by TMS. These findings reveal dose–response relationships between intensity and timing of TMS on visual perception and electrophysiological brain activity, generally indicating greater facilitation at stimulation intensities below RMT.
Ab initio Spillover Compensation in CyTOF Data
Authors: Miao Qi , Wang Fang , Dou Jinzhuang , Iqbal Ramiz , Muftuoglu Muharrem , Basar Rafet , Li Li , Rezvani Katy , Chen Ken 
Published: June 2020

AbstractSignal intensity measured in a mass cytometry (CyTOF) channel can often be affected by the neighboring channels due to technological limitations. Such signal artifacts are known as spillover effects and can substantially limit the accuracy of cell population clustering. Current approaches reduce these effects by using additional beads for normalization purposes known as single-stained controls. While effective in compensating for spillover effects, incorporating single-stained controls can be costly and require customized panel design. This is especially evident when executing large-scale immune profiling studies. We present a novel statistical method, named CytoSpill that independently quantifies and compensates the spillover effects in CyTOF data without requiring the use of single-stained controls. Our method utilizes knowledge-guided modeling and statistical techniques, such as finite mixture modeling and sequential quadratic programming, to achieve optimal error correction. We evaluated our method using five publicly available CyTOF datasets obtained from human peripheral blood mononuclear cells (PBMCs), C57BL/6J mouse bone marrow, healthy human bone marrow, chronic lymphocytic leukemia patient, and healthy human cord blood samples. In the PBMCs with known ground truth, our method achieved comparable results to experiments that incorporated single-stained controls. In datasets without ground-truth, our method not only reduced spillover on likely affected markers, but also led to the discovery of potentially novel subpopulations expressing functionally meaningful, cluster-specific markers. CytoSpill (developed in R) will greatly enhance the execution of large-scale cellular profiling of tumor immune microenvironment, development of novel immunotherapy, and the discovery of immune-specific biomarkers. The implementation of our method can be found athttps://github.com/KChen-lab/CytoSpill.git.
Molecular simulations unravel the molecular principles that mediate selective permeability of carboxysome shell protein
Authors: Faulkner Matthew , Szabó István , Weetman Samantha L. , Sicard Francois , Huber Roland G. , Bond Peter J. , Rosta Edina , Liu Lu-Ning 
Published: June 2020

AbstractBacterial microcompartments (BMCs) are nanoscale proteinaceous organelles that encapsulate enzymes from the cytoplasm using an icosahedral protein shell that resembles viral capsids. Of particular interest are the carboxysomes (CBs), which sequester the CO2-fixing enzymes ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) to enhance carbon assimilation. The carboxysome shell serves as a semi-permeable barrier for passage of metabolites in and out of the carboxysome to enhance CO2 fixation. How the protein shell directs influx and efflux of molecules in an effective manner has remained elusive. Here we use molecular dynamics and umbrella sampling calculations to determine the free-energy profiles of the metabolic substrates, bicarbonate, CO2 and ribulose bisphosphate and the product 3-phosphoglycerate associated with their transition through the major carboxysome shell protein CcmK2. We elucidate the electrostatic charge-based permeability and key amino acid residues of CcmK2 functioning in mediating molecular transit through the central pore. Conformational changes of the loops forming the central pore may also be required for transit of specific metabolites. The importance of these in-silico findings is validated experimentally by site-directed mutagenesis of the key CcmK2 residue Serine 39. This study provides insight into the mechanism that mediates molecular transport through the shells of carboxysomes, applicable to other BMCs. It also offers a predictive approach to investigate and manipulate the shell permeability, with the intend of engineering BMC-based metabolic modules for new functions in synthetic biology.