bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNAs exhibit limited evidence for translation, or translation regulation of the mRNA-counterpart in terminal hematopoiesis
Authors: Nicolet Benoit P. , Jansen Sjoert B.G. , Heideveld Esther , Ouwehand Willem H. , van den Akker Emile , von Lindern Marieke , Wolkers Monika C. 
Published: October 2020

ABSTRACTEach day, about 1012erythrocytes and platelets are released into the blood stream. This substantial output from hematopoietic stem cells is tightly regulated by transcriptional and epigenetic factors. Whether and how circular RNAs (circRNAs) contribute to the differentiation and/or identity of hematopoietic cells is to date not known. We recently reported that erythrocytes and platelets contain the highest levels and numbers of circRNAs amongst hematopoietic cells. Here, we provide the first detailed analysis of circRNA expression during erythroid and megakaryoid differentiation. CircRNA expression not only significantly increased upon enucleation, but also had limited overlap between progenitor cells and mature cells, suggesting that circRNA expression stems from regulated processes rather than resulting from mere accumulation. To study circRNA function in hematopoiesis, we first compared the expression levels of circRNAs with the translation efficiency of their mRNA-counterpart. We found that only 1 out of 2531 (0.04%) circRNAs associated with mRNA-translation regulation. Furthermore, irrespective of 1000s of identified putative open reading frames, deep ribosome-footprinting sequencing and mass spectrometry analysis provided little evidence for translation of endogenously expressed circRNAs. In conclusion, circRNAs alter their expression profile during terminal hematopoietic differentiation, yet their contribution to regulate cellular processes remains enigmatic.
Single-cell Sequencing Reveals Brain/Spinal Cord Oligodendrocyte Precursor Heterogeneity and Requirement for mTOR in Cholesterol Biosynthesis and Myelin Maintenance
Authors: Khandker Luipa , Jeffries Marisa A. , Chang Yun-Juan , Mather Marie L. , Bourne Jennifer N. , Tafreshi Azadeh K. , Ornelas Isis M. , Bozdagi-Gunal Ozlem , Macklin Wendy B. , Wood Teresa L. 
Published: October 2020

AbstractBrain and spinal cord oligodendroglia have distinct functional characteristics, and cell autonomous loss of individual genes can result in different regional phenotypes. However, sequencing studies to date have not revealed distinctions between brain and spinal cord oligodendroglia. Using single-cell analysis of oligodendroglia during myelination, we demonstrate that brain and spinal cord precursors are transcriptionally distinct, defined predominantly by cholesterol biosynthesis. We further identify mechanistic target of rapamycin (mTOR) as a major regulator promoting cholesterol biosynthesis in oligodendroglia. Oligodendroglial-specific loss of mTOR compromises cholesterol biosynthesis in both the brain and spinal cord. Importantly, mTOR loss has a greater impact on cholesterol biosynthesis in spinal cord oligodendroglia that corresponds with more pronounced developmental deficits. However, loss of mTOR in brain oligodendroglia ultimately results in oligodendrocyte death, spontaneous demyelination, and impaired axonal function, demonstrating that mTOR is required for myelin maintenance in the adult brain.
A 9-kDa matricellular SPARC fragment released by cathepsin D exhibits pro-tumor activity in the triple-negative breast cancer microenvironment
Authors: Alcaraz Lindsay B , Mallavialle Aude , David Timothée , Derocq Danielle , Delolme Frédéric , Dieryckx Cindy , Boissière-Michot Florence , Simony-Lafontaine Joëlle , Manoir Stanislas Du , Huesgen Pitter F. , Overall Christopher M. , Tartare-Deckert Sophie , Jacot William , Chardès Thierry , Guiu Séverine , Roger Pascal , Reinheckel Thomas , Moali Catherine , Liaudet-Coopman Emmanuelle 
Published: October 2020

ABSTRACTExtracellular matrix (ECM) remodeling by proteases results in the release of protein fragments that promote tumor progression and metastasis. The protease cathepsin D (cath-D), a marker of poor prognosis in triple-negative breast cancer (TNBC), is aberrantly secreted in the tumor microenvironment. Using degradomic analyses by TAILS, we discovered that the matricellular protein SPARC is a substrate of extracellular cath-D.In vitro, cath-D induced limited proteolysis of SPARC C-terminal extracellular Ca2+binding domain at acidic pH, leading to the production of SPARC fragments (34-, 27-, 16-, 9-, and 6-kDa). Similarly, cath-D secreted by TNBC cells cleaved fibroblast- and cancer cell-derived SPARC at the tumor pericellular acidic pH. SPARC cleavage also occurred in TNBC tumors. Among these fragments, only the 9-kDa SPARC fragment inhibited TNBC cell adhesion and spreading on fibronectin, and stimulated their migration, endothelial transmigration, and invasion. Our study establishes a novel crosstalk between proteases and matricellular proteins in the tumor microenvironment through limited proteolysis of SPARC, revealing a novel targetable 9-kDa bioactive SPARC fragment for new TNBC treatments.
Epstein-Barr virus promotes survival through germinal center light zone chromatin architecture
Authors: Dai Joanne , Heckenberg Emma , Song Lingyun , Crawford Gregory E. , Luftig Micah A. 
Published: October 2020

ABSTRACTBFL-1 is an understudied anti-apoptotic protein upregulated in cancer and Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines (LCLs). We have previously shown that BFL-1 is regulated through viral EBNA3A-mediated alterations in B-cell chromatin conformation (Price et al., 2017). Here, we extend those findings to define cis- and trans-acting factors that regulate BFL-1 in LCLs and reliance on BFL-1 for survival from extrinsic apoptosis. Beyond LCLs, BFL-1 is expressed in B cells maturing in the germinal center (GC). We therefore characterized the gene expression profiles and chromatin landscape of maturing human tonsillar B-cell subsets. While chromatin accessibility at the BFL-1 locus increases as naïve B cells enter the GC reaction, BFL-1 expression increases during the transition from dark zone to light zone (LZ) correlating with association between enhancer regions and the transcriptional start site. The relationship between LCLs and LZ B cells suggests that EBV phenocopies GC biology to enhance their survival in establishing latent infection.
Phosphorylation of the RB C-terminus regulates condensin II release from chromatin
Authors: Kim Seung J. , MacDonald James I. , Dick Frederick A. 
Published: October 2020

ABSTRACTThe retinoblastoma tumour suppressor protein (RB) plays an important role in biological processes such as cell cycle control, DNA damage repair, epigenetic regulation, and genome stability. The canonical model of RB regulation is that cyclin-CDKs phosphorylate, and render RB inactive in late G1/S, promoting entry into S phase. Recently, mono-phosphorylated RB species were described to have distinct cell-cycle independent functions, suggesting that a phosphorylation code dictates diversity of RB function. However, a biologically relevant, functional role of RB phosphorylation at non-CDK sites has remained elusive. Here, we investigated S838/T841 dual phosphorylation, its upstream stimulus, and downstream functional output. We found that mimicking T-cell receptor activation in Jurkat leukemia cells induced sequential activation of downstream kinases including p38 MAPK, and RB S838/T841 phosphorylation. This signaling pathway disrupts RB and condensin II interaction with chromatin. Using cells expressing a WT or S838A/T841A mutant RB fragment, we present evidence that deficiency for this phosphorylation event prevents condensin II release from chromatin.
Slaying the last unicorn - discovery of histones in the microalgaNanochlorum eucaryotum
Authors: Soo Valerie WC , Warnecke Tobias 
Published: October 2020

ABSTRACTHistones are the principal constituents of eukaryotic chromatin. The four core histones (H2A, H2B, H3, and H4) are conserved across sequenced eukaryotic genomes and therefore thought to be universal to eukaryotes. In the early 1980s, however, a series of biochemical investigations failed to find evidence for histones or nucleosomal structures in the microscopic green algaNanochlorum eucaryotum. If true, derived histone loss in this lineage would constitute an exceptional case that might help us further understand the principles governing eukaryotic gene regulation. To substantiate these earlier reports of histone loss inN. eucaryotum,we sequenced, assembled and quantified its transcriptome. Following a systematic search for histone-fold domains in the assembled transcriptome, we detect orthologs to all four core histones. We also find histone mRNAs to be highly expressed, comparable to the situation in other eukaryotes. Finally, we obtain characteristic protection patterns whenN. eucaryotumchromatin is subjected to micrococcal nuclease digestion, indicating widespread formation of nucleosomal complexesin vivo.We conclude that previous reports of missing histones inN. eucaryotumwere mistaken. By all indications,N. eucaryotumhas histone-based chromatin characteristic of most eukaryotes.
MLS3: A New Type of Multilevel Selection
Authors: Jones Christopher T. , Doolittle W. Ford , Susko Edward , Meynell Letitia , Neto Celso A. , Lenton Timothy M. , Bielawski Joseph P. 
Published: October 2020

AbstractIn most multispecies multilevel selection (MLS) models, offspring communities are generated by random assembly of individuals in numbers reflecting sizes of parental communities releasing them (MLS1), or by differential community dispersal based on a community-level trait such as size (MLS2). In both, offspring communitiescolonizevacant spaces: different communities never compete for the same space. Here we propose a third MLS type (MLS3) where multispecies communities disperse (migrate) into already-occupied spaces, larger communities more frequently. Conspecific variants compete, often opposing selection for community size against fitness within species. This makes the outcome of MLS3 less apparent than MLS1 and MLS2 where such tension is absent. Our simulations show that, if community size depends strongly on reduction in the fitness of individual community members, such a reduction (comprising a sort of “inter-species altruism”) will evolve. The framework we present represents a step toward conceptualizingcommunity coalescencein the context of metacommunities.
Analysis of the Functional Differentiation Sites in Vertebrate Neuronal Nicotinic Acetylcholine Receptor Subunits
Authors: Zhao Mengwen , Ma Yuequn , Xin Juncai , Cao Changying , Wang Ju 
Published: October 2020

AbstractThe nicotinic acetylcholine receptors (nAChR) belong to a large family of ligand-gated ion channels and are involved in the mediation of fast synaptic transmission. Each receptor is made up of five subunits that arrange symmetrically around a central pore. Despite the similarity in their sequences and structures, the properties of these subunits vary significantly. Thus, identifying the function-related sites specific to each subunit is essential for understanding the characteristics of the subunits and the receptors assembled by them. In this study, we examined the sequence features of the nine neuronal nAChRs subunits from twelve representative vertebrate species. Analysis revealed that all the subunits were subject to strong purifying selection in evolution, and each was under a unique pattern of selection pressures. At the same time, the functional constraints were not uniform within each subunit, with different domains in the molecule being subject to different selection pressures. Via evolutionary analyses, we also detected potential positive selection events in the subunits or subunit clusters, and identified the sites might be associated with the function specificity of each subunit. Furthermore, positive selection at some domains might contributed to the diversity of subunit function; for example, the β9 strand might be related to the agonist specificity of α subunit in heteromeric receptor and β4-β5 linker could be involved in Ca2+permeability. Subunits α7, α4 and β2 subunits possess a strong adaptability in vertebrates. Our results highlighted the importance of tracking functional differentiation in protein sequence underlying functional properties of nAChRs. In summary, our work may provide clues on understanding the diversity and the function specificity of the nAChR subunits, as well as the receptors co-assembled by them.
Neotype designation and re-description of Forsskål’s reticulate whiprayHimantura uarnak
Authors: Borsa Philippe , Williams Collin T. , McIvor Ashlie J. , Berumen Michael L. 
Published: October 2020

AbstractA serious impediment to the taxonomy of the reticulate whiprayHimanturaspp. species complex has been the absence of a type specimen for P. Forsskål’sH. uarnak. Here, reticulate whipray specimens were sampled from the Jeddah region, the assumed type locality ofH. uarnak, and characterized genetically at the cytochrome-oxidase subunit 1 (CO1) locus. One of these specimens now in the fish collection of the California Academy of Sciences in San Francisco was designated as neotype. A maximum-likelihood phylogeny of all availableCO1gene sequences from the genusHimanturahad the following topology: ((H. leoparda, H. uarnak), (H. undulata, (Himanturasp. 2, (H. australis+Himanturasp. 1))),H. tutul), whereH. uarnakhaplotypes formed a distinct sub-clade sister toH. leoparda. Based on theseCO1gene sequences, the geographic distribution ofH. uarnakincludes the eastern Mediterranean, the Red Sea, the East African coast, and the Arabian Sea. Two lineages in the reticulate whipray species complex remain to be named.NoticeThe present article in portable document (.pdf) format is a published work in the sense of the International Code of Zoological Nomenclature [International Commission on Zoological Nomenclature (ICZN)1999]. It has been registered in ZooBank (http://zoobank.org/), the online registration system for the ICZN. The ZooBank life science identifier for this publication is urn:lsid:zoobank.org:pub:B2113697-5EBF-4364-B50C-63019A1A076A. The online version of this work is archived and available from the bioRxiv (https://biorxiv.org/) repository.
Adenosine diphosphate contributes to wound healing in diabetic mice through P2Y1and P2Y12receptors activation
Authors: Borges Paula A. , Waclawiak Ingrid , Georgii Janaína L. , Barros Janaína F. , Fraga-Junior Vanderlei S. , Lemos Felipe S. , Russo-Abrahão Thaís , Saraiva Elvira M. , Takiya Christina M. , Coutinho-Silva Robson , Penido Carmen , Mermelstein Claudia , Meyer-Fernandes José R. , Canto Fábio B. , Neves Josiane S. , Melo Paulo A. , Canetti Claudio , Benjamim Claudia F. 
Published: October 2020

AbstractSeveral studies have shown the importance of purinergic signaling in various inflammatory diseases. In diabetes mellitus, there is an increase in the activity of some nucleotidases suggesting that this signaling may be affected in the diabetic skin. Thus, the aim of our study was to investigate the effect of ADP on wound healing in diabetic skin. Swis and C57BL/6 mice were pharmacologic induced to type 1 diabetes and submitted to a full-thickness excisional wound model to evaluate the effect of ADP as a topic treatment. Adenosine diphosphate accelerated cutaneous wound healing, improved the new tissue formation, and increased collagen deposit by positively modulating P2Y1and P2Y12and TGF-β production. In parallel, ADP reduced reactive oxygen species production and TNF-αlevels, while increased IFNγ, IL-10 and IL-13 levels in the skin. Also, ADP induced the migration of neutrophils, eosinophils, mast cells, TCRγ4+, and TCRγ5+cells while reduced Treg cells towards the lesion at day 7. In accordance, ADP increased the proliferation and migration of fibroblast, induced myofibroblast differentiation and keratinocyte proliferation in a P2Y12-dependent manner. We provide the first evidence of ADP acting as a potent mediator on skin wound resolution and a possible therapeutic approach for diabetic patients worldwide.
Deciphering the Agonist Binding Mechanism to the Adenosine A1 Receptor
Authors: Deganutti Giuseppe , Barkan Kerry , Preti Barbara , Leuenberger Michele , Wall Mark , Frenguelli Bruno , Lochner Martin , Ladds Graham , Reynolds Christopher A 
Published: October 2020

ABSTRACTDespite being amongst the most characterized G protein-coupled receptors (GPCRs), adenosine receptors (ARs) have always been a difficult target in drug design. To date, no agonist other than the natural effector and the diagnostic regadenoson has been approved for human use. Recently, the structure of the adenosine A1 receptor (A1R) was determined in the active, Giprotein complexed state; this has important repercussions for structure-based drug design. Here, we employed supervised molecular dynamics simulations and mutagenesis experiments to extend the structural knowledge of the binding of selective agonists to A1R. Our results identify new residues involved in the association and dissociation pathway, suggest the binding mode of N6-cyclopentyladenosine (CPA) related ligands, and highlight the dramatic effect that chemical modifications can have on the overall binding mechanism.
LPA/PKD-1 signaling promotes development of arteriolar niche that supports self-renewal of breast cancer stem cells and stemness
Authors: Jiang Yinan , Guo Yichen , Hao Jinjin , Guenter Rachael , Lathia Justin , Beck Adam , Hattaway Reagan , Hurst Doug , Wang Q Jane , Liu Yehe , Cao Qi , Krontiras Helen , Chen Herbert , Silverstein Roy , Ren Bin 
Published: October 2020

ABSTRACTBreast cancer stem cells (BCSCs) are essential for cancer growth, metastasis and recurrence. However, the regulatory mechanisms of self-renewal and interactions with the vascular niche within tumor microenvironment are currently under investigation. Here, we demonstrate that BCSCs are enriched within arteriolar niche within the tumor microenvironment of estrogen receptor positive (ER+) BC and bi-directionally interact with arteriolar endothelial cells (ECs). Mechanistically, this interaction is driven by the LPA/PKD-1 signaling pathway, which promotes arteriolar differentiation and self-renewal. Furthermore, this pathway directly promotes stemness features. These findings suggest that targeting LPA/PKD-1 signaling may disrupt the arteriolar niche within the tumor microenvironment and concomitantly eradicate BCSCs, thereby attenuating BC progression.
Spinal cord precursors utilize neural crest cell mechanisms to generate hybrid peripheral myelinating glia
Authors: Fontenas Laura , Kucenas Sarah 
Published: October 2020

AbstractDuring development, oligodendrocytes and Schwann cells myelinate central and peripheral nervous system axons, respectively, while motor exit point (MEP) glia are neural tube-derived, peripheral glia that myelinate axonal territory between these populations at MEP transition zones. From which specific neural tube precursors MEP glia are specified, and how they exit the neural tube to migrate onto peripheral motor axons, remain largely unknown. Here, using zebrafish, we found that MEP glia arise from lateral floor plate precursors and requirefoxd3to delaminate and exit the spinal cord. Additionally, we show that similar to Schwann cells, MEP glial development depends on axonally-derivedneuregulin1. Finally, our data demonstrate that overexpressing axonal cues is sufficient to generate additional MEP glia in the spinal cord. Overall, these studies provide new insight into how a novel population of hybrid, peripheral myelinating glia are generated from neural tube precursors and migrate into the periphery.
Entrepreneurship education and entrepreneurial intentions of university students in Vietnam: the mediating roles of self-efficacy and learning orientation
Authors: Hoang Giang , Le Thuy Thu Thi , Tran Anh Kim Thi , Du Tuan 
Published: October 2020

PurposeThis study aims to explore the mediating roles of self-efficacy and learning orientation in the relationship between entrepreneurship education and entrepreneurial intentions of university students in Vietnam.Design/methodology/approachThe data were collected from an online survey of 1,021 university students in Vietnam. The authors conducted a hierarchical regression analysis to test the hypotheses.FindingsThe results of hierarchical regression analysis reveal that entrepreneurship education positively affects entrepreneurial intentions, and this relationship is mediated by both learning orientation and self-efficacy.Research limitations/implicationsThis study confirms the importance of entrepreneurship education in encouraging university students' entrepreneurial intentions.Practical implicationsThis study offers practical implications for universities and policy makers.Social implicationsThis study is one of the first to empirically examine the concept of entrepreneurship education and entrepreneurial intentions in an Asia-Pacific context.Originality/valueThis study emphasises the significance of entrepreneurship education and its effects on university students' entrepreneurial intentions. Furthermore, the findings confirm that self-efficacy and learning orientation play an important part in explaining how entrepreneurship education relates to entrepreneurial intentions.
Effect of the auditor’s behavioral and individual characteristics on integrated reporting quality: evidence from European companies
Authors: Chouaibi Jamel , Hichri Abir 
Published: October 2020

Purpose
The purpose of this paper is to consist in examining the effect of the auditor’s behavioral and individual characteristics on the integrated reporting quality, in regard to a sample involving 130 European industrial companies, relevant to the year 2017.

Design/methodology/approach
The present study’s adopted methodology rests on the hypothetico-deductive approach. The relevant data applied are analyzed by means of multiple linear regression models.

Findings
The reached results prove to indicate well that both auditor specialization and auditor ethics factors appear to have a significantly positive effect on the integrated reporting quality. Noteworthy, also, is the fact that the audit firm size and auditor behavior have been discovered to have a positive and insignificant effect on the integrated reporting related quality.

Originality/value
Faced with the scarcity of studies linking the auditor characteristics and the integrated reporting quality, the present study is elaborated to provide some kind of modest contribution, whereby, the determinants of integrated reporting are distinguishably highlighted