bluuebunny/crossref_metadata_2025_split huggingface dataset:
Who is the best surrogate for germ stem cell transplantation in fish?
Authors: Franěk Roman , Cheng Yu , Fučíková Michaela , Kašpar Vojtěch , Xie Xuan , Shah Mujahid Ali , Linhart Otomar , Šauman Ivo , Pšenička Martin 
Published: August 2021

ABSTRACTSurrogate reproduction technology in fish has potential for aquaculture as well as endangered species preservation and propagation. Species with some unfavourable biological characteristics for culturing such as a late maturation or a large body size are ideal candidates for surrogate reproduction using smaller and faster-maturing host. One of the general prerequisites for the successful surrogacy and the pure donor-derived gamete production is the sterility of the host. Various sterilization methods have been developed and used in fish surrogacy; however, a direct comparison of available methods is missing. Such a knowledge gap hinders choice for the surrogate in various fish species, including those in high commercial demand such as tuna or sturgeons, where is a particular limitation from the point of the live material availability and difficulty to perform a high throughput assessment of different surrogates. Yet, large sturgeons or tuna species are one of the most prominent candidates for surrogacy. Zebrafish was utilized in this study as a model species to answer whether and to which extent different sterilization strategies can affect the surrogacy. Germ cell-depleted recipients (produced using knockdown of dead end gene), triploid recipients, and zebrafish x pearl danio hybrid recipients were tested as they represent the most frequently used types of surrogates. Spermatogonia isolated from vas::EGFP transgenic strain were intraperitoneally transplanted into swim-up 5-day old zebrafish. Transplantation success, survival, gonadal development, and reproductive output of the fish was analyzed. Germ cell-depleted recipients with empty gonads were identified as the most convenient among tested sterilization methods considering surrogacy induction success and reproductive output. The present study stands as significant aid for selecting suitable surrogates in various fish species.
Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells
Authors: Calvert BA , Quiroz EJ , Lorenzana Z , Doan N , Kim S , Senger CN , Wallace WD , Salomon MP , Henley J , Ryan AL 
Published: August 2021

AbstractIn response to viral infection, neutrophils release inflammatory mediators as part of the innate immune response, contributing to pathogen clearance through virus internalization and killing. Pre-existing co- morbidities correlating to incidence of severe COVID-19 are associated with chronic airway neutrophilia. Furthermore, examination of COVID-19 explanted lung tissue revealed a series of epithelial pathologies associated with the infiltration and activation of neutrophils, indicating neutrophil activity in response to SARS- CoV-2 infection. To determine the impact of neutrophil-epithelial interactions on the infectivity and inflammatory responses to SARS-CoV-2 infection, we developed a co-culture model of airway neutrophilia. SARS-CoV-2 infection of the airway epithelium alone does not result in a notable pro-inflammatory response from the epithelium. The addition of neutrophils induces the release of proinflammatory cytokines and stimulates a significantly augmented pro-inflammatory response subsequent SARS-CoV-2 infection. The resulting inflammatory response is polarized with differential release from the apical and basolateral side of the epithelium. Additionally, the integrity of the epithelial barrier is impaired with notable epithelial damage and infection of basal stem cells. This study reveals a key role for neutrophil-epithelial interactions in determining inflammation and infectivity in response to SARS-CoV-2 infection.
SIGNR1 promotes immune dysfunction in systemic candidiasis by modulating neutrophil lifespan via T cell-derived histones and G-CSF
Authors: Ioannou Marianna , Hoving Dennis , Aramburu Iker Valle , De Vasconcelos Nathalia M. , Temkin Mia I. , Wang Qian , Vernardis Spyros , Demichev Vadim , Tsourouktsoglou Theodora-Dorita , Boeing Stefan , Goldstone Robert , David Sascha , Stahl Klaus , Bode Christian , Ralser Markus , Papayannopoulos Venizelos 
Published: August 2021

SummaryThe mechanisms regulating immune dysfunction during sepsis are poorly understood. Here, we show that neutrophil-derived myeloperoxidase delays the onset of immune dysfunction during systemic candidiasis by controlling microbes captured by splenic marginal zone (MZ) macrophages. In contrast, SIGNR1-mediated microbe capture accelerates MZ colonization and immune dysfunction by triggering T cell death, T cell-dependent chromatin release and the synergistic induction of G-CSF by histones and fungi. Histones and G-CSF promote the prevalence of immature Ly6Glowneutrophils with defective oxidative burst, by selectively shortening the lifespan of mature Ly6Ghighneutrophils. Consistently, T cell deficiency, or blocking SIGNR1, G-CSF or histones delayed neutrophil dysfunction. Furthermore, histones and G-CSF in the plasma of sepsis patients, shortened neutrophil lifespan and correlated with neutrophil mortality markers associated with a poor prognosis. Hence, the compromise of internal antimicrobial barrier sites drives neutrophil dysfunction by selectively modulating neutrophil lifespan via pathogenic T cell death, extracellular histones, and G-CSF.
Diauxic lags explain unexpected coexistence in multi-resource environments
Authors: Bloxham William , Lee Hyunseok , Gore Jeff 
Published: August 2021

AbstractHow the coexistence of species is affected by the presence of multiple resources is a major question in microbial ecology. We experimentally demonstrate that differences in diauxic lags, which occur as species deplete their own environments and adapt their metabolisms, allow slow-growing microbes to stably coexist with faster-growing species in multi-resource environments despite being excluded in single-resource environments. In our focal example, an Acinetobacter species (Aci2) competitively excludes Pseudomonas aurantiaca (Pa) on alanine and on glutamate. However, they coexist on the combination of both resources. Experiments reveal that Aci2 grows faster but Pa has shorter diauxic lags. We establish a tradeoff between Aci2’s fast growth and Pa’s short lags as their mechanism for coexistence. We model this tradeoff to accurately predict how environmental changes affect community composition. We extend our work by surveying a large set of competitions and observe coexistence nearly three times as frequently when the slow-grower is the fast-switcher. Our work illustrates a potentially common mechanism for the emergence of multi-resource coexistence despite single-resource competitive exclusions.
A Systematic Comparison of Differential Analysis Methods for CyTOF Data
Authors: Arend Lis , Bernett Judith , Manz Quirin , Klug Melissa , Lazareva Olga , Baumbach Jan , Bongiovanni Dario , List Markus 
Published: August 2021

AbstractCytometry techniques are widely used to discover cellular characteristics at single-cell resolution. Many data analysis methods for cytometry data focus solely on identifying subpopulations via clustering and testing for differential cell abundance. For differential expression analysis of markers between conditions, only few tools exist. These tools either reduce the data distribution to medians, discarding valuable information, or have underlying assumptions that may not hold for all expression patterns.Here, we systematically evaluated existing and novel approaches for differential expression analysis on real and simulated CyTOF data. We found that methods using median marker expressions compute fast and reliable results when the data is not strongly zero-inflated. Methods using all data detect changes in strongly zero-inflated markers, but partially suffer from overprediction or cannot handle big datasets. We present a new method, CyEMD, based on calculating the Earth Mover’s Distance between expression distributions that can handle strong zero-inflation without being too sensitive.Additionally, we developed CYANUS, a user-friendly R Shiny App allowing the user to analyze cytometry data with state-of-the-art tools, including well-performing methods from our comparison. A public web interface is available at https://exbio.wzw.tum.de/cyanus/.
Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model
Authors: Wang Guang , Wang Yongfeng , Li Jianglan , Peng Ruji , Liang Xinyin , Chen Xuedong , Jiang Guihua , Shi Jinfang , Si-ma Yanghu , Xu Shiqing 
Published: August 2021

AbstractHyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC). It is often clinically complicated by malignant diseases or severe infections. Research on the molecular mechanism of High PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate, Bombyx mori, to investigate the effect of HPPC on circulating blood cells. We showed that HPPC affected blood cell homeostasis and enhanced blood cell phagocytosis, leading to increased reactive oxygen species levels, and induced programmed cell death that depended on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the JAK/STAT signaling pathway. Supplementation with endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Herein, we reported a novel signaling pathway by which HPPC affected blood cell homeostasis, which was different from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early monitoring index for hyperproteinemia.Highlights•HPPC induced proliferation of circulating blood cells through the JAK/STAT pathway, leading to a significant increase in the proportion of granulocytes.•Supplementing endocrine hormone 20E improved hematopoietic function and restored the homeostasis of circulating blood cells through modulation of the JAK/STAT signaling pathway.•HPPC induced PCD in blood cells through the endoplasmic reticulum-calcium ion release signaling pathway.•Down-regulation of the gene expression of the hematopoietic factor Gcm could be used as a potential early monitoring index for hyperproteinemia.
The developing epicardium regulates cardiac chamber morphogenesis by promoting cardiomyocyte growth
Authors: Boezio Giulia L. M. , Gollin Josephine , Zhao Shengnan , Priya Rashmi , Mansingh Shivani , Guenther Stefan , Fukuda Nana , Gunawan Felix , Stainier Didier Y. R. 
Published: August 2021

AbstractThe epicardium, the outermost layer of the heart, is an important regulator of cardiac regeneration. However, a detailed understanding of the crosstalk between the epicardium and myocardium during development requires further investigation. Here, we generated three models of epicardial impairment in zebrafish by mutating the transcription factor genestcf21andwt1a, and by ablatingtcf21+epicardial cells. Notably, all three epicardial-impairment models exhibit smaller ventricles. We identified the initial cause of this phenotype as defective cardiomyocyte growth, resulting in reduced cell surface and volume. This failure of cardiomyocytes to grow is followed by decreased proliferation and increased abluminal extrusion. By temporally manipulating its ablation, we show that the epicardium is required to support ventricular growth during early cardiac morphogenesis. By transcriptomic profiling of sorted epicardial cells, we identified reduced expression of FGF and VEGF ligand genes intcf21-/-hearts, and pharmacological inhibition of these signaling pathways partially recapitulated the ventricular growth defects. Thus, the analysis of these epicardial-impairment models further elucidates the distinct roles of the epicardium during cardiac morphogenesis and the signaling pathways underlying epicardial-myocardial crosstalk.
Phox2bmutation mediated byAtoh1expression impaired respiratory rhythm and ventilatory responses to hypoxia and hypercapnia
Authors: Ferreira Caroline B. , Silva Talita M. , Silva Phelipe E. , Czeisler Catherine , Otero Jose J. , Takakura Ana C. , Moreira Thiago S. 
Published: August 2021

AbstractRetrotrapezoid nucleus (RTN) neurons are involved in central chemoreception and respiratory control. Lineage tracing studies demonstrate RTN neurons to be derived fromPhox2bandAtoh1expressing progenitor cells in rhombere 4.Phox2bexon 3 mutations cause congenital central hypoventilation syndrome (CCHS), producing an impaired respiratory response to hypercapnia and hypoxia. Our goal was to investigate the extent to which a conditional mutation ofPhox2bwithinAtoh1-derived cells might affect a) respiratory rhythm; b) ventilatory responses to hypercapnia and hypoxia and c) number of RTN-chemosensitive neurons. Here, we used a transgenic mouse line carrying a conditionalPhox2bΔ8mutation activated by cre-recombinase. We crossed them withAtoh1Cremice. Ventilation was measured by whole body plethysmograph during neonate and adult life. In room air, experimental and control groups showed similar basal ventilation; however,Atoh1Cre/Phox2bΔ8increased breath irregularity. The hypercapnia and hypoxia ventilatory responses were impaired in neonates. In contrast, adult mice recovered ventilatory response to hypercapnia, but not to hypoxia. Anatomically, we observed a reduction of the Phox2b+/TH−expressing neurons within the RTN region. Our data indicates that conditionally expression ofPhox2bmutation byAtoh1affect development of the RTN neurons and are essential for the activation of breathing under hypoxic and hypercapnia condition, providing new evidence for mechanisms related to CCHS neuropathology.
Moving translational mass spectrometry imaging towards transparent and reproducible data analyses: A case study of an urothelial cancer cohort analyzed in the Galaxy framework
Authors: Föll Melanie Christine , Volkmann Veronika , Enderle-Ammour Kathrin , Wilhelm Konrad , Guo Dan , Vitek Olga , Bronsert Peter , Schilling Oliver 
Published: August 2021

ABSTRACTBackgroundMass spectrometry imaging (MSI) derives spatial molecular distribution maps directly from clinical tissue specimens. This allows for spatial characterization of molecular compositions of different tissue types and tumor subtypes, which bears great potential for assisting pathologists with diagnostic decisions or personalized treatments. Unfortunately, progress in translational MSI is often hindered by insufficient quality control and lack of reproducible data analysis. Raw data and analysis scripts are rarely publicly shared. Here, we demonstrate the application of the Galaxy MSI tool set for the reproducible analysis of an urothelial carcinoma dataset.MethodsTryptic peptides were imaged in a cohort of 39 formalin-fixed, paraffin-embedded human urothelial cancer tissue cores with a MALDI-TOF/TOF device. The complete data analysis was performed in a fully transparent and reproducible manner on the European Galaxy Server. Annotations of tumor and stroma were performed by a pathologist and transferred to the MSI data to allow for supervised classifications of tumor vs. stroma tissue areas as well as for muscle-infiltrating and non-muscle invasive urothelial carcinomas. For putative peptide identifications, m/z features were matched to the MSiMass list.ResultsRigorous quality control in combination with careful pre-processing enabled reduction of m/z shifts and intensity batch effects. High classification accuracy was found for both, tumor vs. stroma and muscle-infiltrating vs. non-muscle invasive tumors. Some of the most discriminative m/z features for each condition could be assigned a putative identity: Stromal tissue was characterized by collagen type I peptides and tumor tissue by histone and heat shock protein beta-1 peptides.Intermediate filaments such as cytokeratins and vimentin were discriminative between the tumors with different muscle-infiltration status. To make the study fully reproducible and to advocate the criteria of FAIR (findability, accessibility, interoperability, and reusability) research data, we share the raw data, spectra annotations as well as all Galaxy histories and workflows. Data are available via ProteomeXchange with identifier PXD026459 and Galaxy results viahttps://github.com/foellmelanie/Bladder_MSI_Manuscript_Galaxy_links.ConclusionHere, we show that translational MSI data analysis in a fully transparent and reproducible manner is possible and we would like to encourage the community to join our efforts.
Interactions of the Trypanosoma brucei brucei zinc-finger-domain protein ZC3H28
Authors: Bishola Tania , Clayton Christine 
Published: August 2021

AbstractIn Trypanosoma brucei and related Kinetoplastids, regulation of gene expression occurs mostly post-transcriptionally, and RNA-binding proteins play a critical role in the regulation of mRNA and protein abundance. Trypanosoma brucei ZC3H28 is a 114 KDa cytoplasmic mRNA-binding protein with a single C(x)7C(x)5C(x)sH zinc finger at the C-terminus and numerous proline-, histine- or glutamine-rich regions. We here show that N-terminally tagged ZC3H28 copurifies ribosomes, various RNA-binding proteins, and the translation initiation complex EIF4E4/EIF4G3. ZC3H28 is preferentially associated with long RNAs that have low complexity sequences in their 3’-untranslated regions. When tethered to a reporter mRNA, ZC3H28 increased the mRNA level without a corresponding increase in protein expression; this suggests that it stabilized the reporter but at the same time suppressed its translation. Indeed, there was a clear negative correlation between ZC3H28 mRNA binding and ribosome density. After ZC3H28 depletion, the relative levels of ribosomal protein mRNAs increased while levels of some long mRNAs decreased, but there is no overall correlation between binding and RNAi effects on mRNA abundance. We speculate that ZC3H28 might be implicated in stabilizing poorly-translated mRNAs.
PRC1 Sustains the Memory of Neuronal Fate Independent of PRC2 Function
Authors: Sawai Ayana , Pfennig Sarah , Bulajić Milica , Miller Alexander , Khodadadi-Jamayran Alireza , Mazzoni Esteban O. , Dasen Jeremy S. 
Published: August 2021

AbstractPolycomb repressive complexes (PRCs) 1 and 2 maintain stable cellular memories of early fate decisions by establishing heritable patterns of gene repression. PRCs repress transcription through histone modifications and chromatin compaction, but their roles in neuronal subtype diversification are poorly defined. We unexpectedly found that PRC2 is dispensable to preserve the morphogen-induced positional fates of spinal motor neurons (MNs), while PRC1 is essential for the specification of segmentally-restricted subtypes. Mutation of the core PRC1 componentRing1in mice leads to increased chromatin accessibility and ectopic expression of a broad variety of fates determinants, including Hox transcription factors, while neuronal class-specific features are maintained. Loss of MN subtype identities inRing1mutants is due to the suppression of Hox networks by derepressed caudalHoxgenes. These results indicate that PRC1 can function independently ofde novoPRC2-dependent histone methylation to maintain chromatin topology and transcriptional memory at the time of neuronal differentiation.
isotracer: An R package for the analysis of tracer addition experiments
Authors: Bruneaux Matthieu , López-Sepulcre Andrés 
Published: August 2021

AbstractTracer addition experiments, particularly using isotopic tracers, are becoming increasingly important in a variety of studies aiming at characterizing the flows of molecules or nutrients at different levels of biological organization, from the cellular and tissue levels, to the organismal and ecosystem levels.We present an approach based on Hidden Markov Models (HMM) to estimate nutrient flow parameters across a network, and its implementation in the R package isotracer.The isotracer package is capable of handling a variety of tracer study designs, including continuous tracer drips, pulse experiments, and pulse-chase experiments. It can also take into account tracer decay when radioactive isotopes are used.To illustrate its use, we present three case studies based on published data and spanning different levels of biological organization: a molecular-level study of protein synthesis and degradation inArabidopsis thaliana, an organismal-level study of phosphorus incorporation in the eelgrassZostera marina, and an ecosystem-level study of nitrogen dynamics in Trinidadian montane streams.With these case studies, we illustrate how isotracer can be used to estimate uptake rates, turnover rates, and total flows, as well as their uncertainty. We also show how to perform model selection to compare alternative hypotheses.We conclude by discussing isotracer’s further applications, limitations, and possible future improvements and expansions.
A Capped Tudor Domain within a Core Subunit of the Sin3L/Rpd3L Histone Deacetylase Complex Binds Nucleic Acids
Authors: Marcum Ryan Dale , Hsieh Joseph , Giljen Maksim , Zhang Yongbo , Radhakrishnan Ishwar 
Published: August 2021

AbstractChromatin-modifying complexes containing histone deacetylase (HDAC) activities play critical roles in the regulation of gene transcription in eukaryotes. These complexes are thought to lack intrinsic DNA-binding activity, but according to a well-established paradigm, they are recruited via protein-protein interactions by gene-specific transcription factors and post-translational histone modifications to their sites of action on the genome. The mammalian Sin3L/Rpd3L complex, comprising more than a dozen different polypeptides, is an ancient HDAC complex found in diverse eukaryotes. The subunits of this complex harbor conserved domains and motifs of unknown structure and function. Here we show that Sds3, a constitutively associated subunit critical for the proper functioning of the complex, harbors a type of Tudor domain that we designate the capped Tudor domain (CTD). Unlike canonical Tudor domains that bind modified histones, the Sds3 CTD binds to nucleic acids that can form higher-order structures such as G-quadruplexes, and shares similarities with the knotted Tudor domain of the Esa1 histone acetyltransferase (HAT) that was previously shown to bind single-stranded RNA. Our findings expand the range of macromolecules capable of recruiting the Sin3L/Rpd3L complex and draws attention to potentially new roles for this HDAC complex in transcription biology.
LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants
Authors: Alasiri A. , Karczewski K. J. , Cole B. , Loza B. , Moore J. H. , van der Laan S. W. , Asselbergs F. W. , Keating B. J. , van Setten J. 
Published: August 2021

AbstractMotivationLoss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.ResultsWe have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from both genotyped and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.Availability and implementationLoFTK is an open source software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTKContactj.vansetten@umcutrecht.nlSupplementary informationSupplementary data are available at Bioinformatics online.