bluuebunny/crossref_metadata_2025_split huggingface dataset:
Architecture of the cortical actomyosin network driving apical constriction inC. elegans
Authors: Zhang Pu , Medwig-Kinney Taylor N. , Goldstein Bob 
Published: February 2023

AbstractApical constriction is a cell shape change that drives key morphogenetic events during development, including gastrulation and neural tube formation. The forces driving apical constriction are primarily generated through the contraction of apicolateral and/or medioapical actomyosin networks. In theDrosophilaventral furrow, the medioapical actomyosin network has a sarcomere-like architecture, with radially polarized actin filaments and centrally enriched non-muscle myosin II and myosin activating kinase. To determine if this is a broadly conserved actin architecture driving apical constriction, we examined actomyosin architecture duringC. elegansgastrulation, in which two endodermal precursor cells internalize from the surface of the embryo. Quantification of protein localization showed that neither the non-muscle myosin II NMY-2 nor the myosin-activating kinase MRCK-1 is enriched at the center of the apex. Further, visualization of barbed- and pointed-end capping proteins revealed that actin filaments do not exhibit radial polarization at the apex. Taken together with observations made in other organisms, our results demonstrate that diverse actomyosin architectures are used in animal cells to accomplish apical constriction.SummaryThrough live-cell imaging of endogenously-tagged proteins, Zhang, Medwig-Kinney, and Goldstein show that the medioapical actomyosin network driving apical constriction duringC. elegansgastrulation is organized diffusely, in contrast to the sarcomere-like architecture previously observed in theDrosophilaventral furrow.
Assessing the biogeography of marine giant viruses in four oceanic transects
Authors: Ha Anh D. , Moniruzzaman Mohammad , Aylward Frank O. 
Published: February 2023

AbstractViruses of the phylumNucleocytoviricotaare ubiquitous in ocean waters and play important roles in shaping the dynamics of marine ecosystems. In this study, we leveraged the bioGEOTRACES metagenomic dataset collected across the Atlantic and Pacific Oceans to investigate the biogeography of these viruses in marine environments. We identified 330 viral genomes, including 212 in the orderImiterviralesand 54 in the orderAlgavirales. We found that most viruses appeared to be prevalent in shallow waters (<150 meters), and that viruses of theMesomimiviridae(Imitervirales) andPrasinoviridae(Algavirales) are by far the most abundant and diverse groups in our survey. Five mesomimiviruses and one prasinovirus are particularly widespread in oligotrophic waters; annotation of these genomes revealed common stress response systems, photosynthesis-associated genes, and oxidative stress modulation that may be key to their broad distribution in the pelagic ocean. We identified a latitudinal pattern in viral diversity in one cruise that traversed the North and South Atlantic Ocean, with viral diversity peaking at high latitudes of the northern hemisphere. Community analyses revealed three distinctNucleocytoviricotacommunities across latitudes, categorized by latitudinal distance towards the equator. Our results contribute to the understanding of the biogeography of these viruses in marine systems.
Left-hemisphere cortical language regions respond equally to observed dialogue and monologue
Authors: Olson Halie , Chen Emily , Lydic Kirsten , Saxe Rebecca 
Published: February 2023

AbstractMuch of the language we encounter in our everyday lives comes in the form of conversation, yet the majority of research on the neural basis of language comprehension has used input from only one speaker at a time. 20 adults were scanned while passively observing audiovisual conversations using functional magnetic resonance imaging. In a block-design task, participants watched 20-second videos of puppets speaking either to another puppet (the “dialogue” condition) or directly to the viewer (“monologue”), while the audio was either comprehensible (played forward) or incomprehensible (played backward). Individually functionally-localized left-hemisphere language regions responded more to comprehensible than incomprehensible speech but did not respond differently to dialogue than monologue. In a second task, participants watched videos (1-3 minutes each) of two puppets conversing with each other, in which one puppet was comprehensible while the other’s speech was reversed. All participants saw the same visual input but were randomly assigned which character’s speech was comprehensible. In left-hemisphere cortical language regions, the timecourse of activity was correlated only among participants who heard the same character speaking comprehensibly, despite identical visual input across all participants. For comparison, some individually-localized theory of mind regions and right hemisphere homologues of language regions responded more to dialogue than monologue in the first task, and in the second task, activity in some regions was correlated across all participants regardless of which character was speaking comprehensibly. Together, these results suggest that canonical left-hemisphere cortical language regions are not sensitive to differences between observed dialogue and monologue.
Borrelia burgdorferiPlzA is a cyclic-di-GMP dependent DNA and RNA binding protein
Authors: Jusufovic Nerina , Krusenstjerna Andrew C. , Savage Christina R. , Saylor Timothy C. , Brissette Catherine A. , Zückert Wolfram R. , Schlax Paula J. , Motaleb Md A. , Stevenson Brian 
Published: February 2023

ABSTRACTThe PilZ domain-containing protein, PlzA, is the only known cyclic di-GMP binding protein encoded by all Lyme disease spirochetes. PlzA has been implicated in the regulation of many borrelial processes, but the effector mechanism of PlzA was not previously known. Here we report that PlzA can bind DNA and RNA and that nucleic acid binding requires c-di-GMP, with the affinity of PlzA for nucleic acids increasing as concentrations of c-di-GMP were increased. A mutant PlzA that is incapable of binding c-di-GMP did not bind to any tested nucleic acids. We also determined that PlzA interacts predominantly with the major groove of DNA and that sequence length plays a role in DNA binding affinity. PlzA is a dual-domain protein with a PilZ-like N-terminal domain linked to a canonical C-terminal PilZ domain. Dissection of the domains demonstrated that the separated N-terminal domain bound nucleic acids independently of c-di-GMP. The C-terminal domain, which includes the c-di-GMP binding motifs, did not bind nucleic acids under any tested conditions. Our data are supported by computational docking, which predicts that c-di-GMP binding at the C-terminal domain stabilizes the overall protein structure and facilitates PlzA-DNA interactions via residues in the N-terminal domain. Based on our data, we propose that levels of c-di-GMP during the various stages of the enzootic life cycle direct PlzA binding to regulatory targets.
CRISPR-based editing of the ω- and γ-gliadin gene clusters reduces wheat immunoreactivity without affecting grain protein quality
Authors: Yu Zitong , Yunusbaev Ural , Fritz Allan , Tilley Michael , Akhunova Alina , Trick Harold , Akhunov Eduard 
Published: February 2023

ABSTRACTWheat immunotoxicity is associated with abnormal reaction to gluten-derived peptides. Attempts to reduce immunotoxicity using breeding and biotechnology often affect dough quality. Here, the multiplexed CRISPR-Cas9 editing of cultivar Fielder was used to modify the ω -and γ-gliadin gene clusters abundant in immunoreactive peptides identified in the genomes assembled using the long-read sequencing technologies. The whole genome sequencing of an edited line showed editing or deletion of nearly all ω-gliadin and half of the γ-gliadin gene copies and lack of editing in the α/β-gliadin genes. The detected 62% and 52% reduction in ω- and γ-gliadin content, respectively, had no negative impact on grain protein quality. A 47-fold immunoreactivity reduction compared to wild-type was detected using antibodies against immunotoxic peptides. Our results indicate that genome profiling to identify gliadin gene copies abundant in immunoreactive peptides and their targeted editing could be an effective mean for reducing immunotoxicity of wheat cultivars while minimizing the impact of editing on protein quality.
The role of pneumococcal extracellular vesicles on the pathophysiology of the kidney disease Hemolytic Uremic Syndrome
Authors: Battista Miriana , Hoffmann Bianca , Bachelot Yann , Zimmermann Lioba , Teuber Laura , Jost Aurélie , Linde Susanne , Westermann Martin , Müller Mario M. , Slevogt Hortense , Hammerschmidt Sven , Figge Marc Thilo , Vilhena Cláudia , Zipfel Peter F. 
Published: February 2023

AbstractStreptococcus pneumoniae-induced hemolytic uremic syndrome (Sp-HUS) is a kidney disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. This disease is frequently underdiagnosed and its pathophysiology is poorly understood. In this work, we compared clinical strains, isolated from infant Sp-HUS patients, to a reference pathogenic strain D39, for host cytotoxicity and further explored the role of Sp-derived extracellular vesicles (EVs) in the pathogenesis of a HUS infection. In comparison with the WT strain, pneumococcal HUS strains caused significant lysis of human erythrocytes and increased the release of hydrogen peroxide. Isolated Sp-HUS EVs were characterized by performing dynamic light-scattering microscopy and proteomic analysis. Sp-HUS strain released EVs at a constant concentration during growth, yet the size of the EVs varied and several subpopulations emerged at later time points. The cargo of the Sp-HUS EVs included several virulence factors at high abundance, i.e., the ribosomal subunit assembly factor BipA, the Pneumococcal Surface Protein A (PspA), the lytic enzyme LytC, several sugar utilization and fatty acid synthesis proteins. Sp-HUS EVs strongly downregulated the expression of the endothelial surface marker PECAM-1 and were internalized by human endothelial cells. Sp-HUS EVs elicited the release of pro-inflammatory cytokines (IL-1ß, IL-6) and chemokines (CCL2, CCL3, CXCL1) by human monocytes. These findings shed new light on the overall function of Sp-EVs, in the scope of infection-mediated HUS, and suggest new avenues of research for exploring the usefulness of Sp-EVs as therapeutic and diagnostic targets.ImportanceStreptococcus pneumoniaeis a life-threatening human pathogen associated with severe illnesses in the upper respiratory tract. Disseminated infections also occur, as the kidney disease hemolytic uremic syndrome. Even though vaccination is available, this pathogen is responsible for a worldwide high mortality rate, especially among children from least developed countries, where vaccination strategies are poor or inexistent. It is estimated that 30% of invasive pneumococcal diseases are caused by antibiotic resistant bacteria, leading to the classification of “serious threat” by the World Health Organization. In order to prevent cases of severe illness, investigation in the direction of new vaccine candidates is of upmost importance. Pneumococcal extracellular vesicles pose as ideal candidates for a serotype-independent vaccine formulation. To this purpose, the aspects of vesicle formation, cargo allocation and function need to be understood in detail.Graphical Abstract
Glycoproteomics-compatible MS/MS-based quantification of glycopeptide isomers
Authors: Maliepaard Joshua C.L. , Damen J. Mirjam A. , Boons Geert-Jan P.H. , Reiding Karli R. 
Published: February 2023

ABSTRACTGlycosylation is an essential protein modification occurring on the majority of extracellular human proteins, mass spectrometry (MS) being an indispensable tool for its analysis. Not only can MS determine glycan compositions, but also position the glycan at specific sites via glycoproteomics. However, glycans are complex branching structures with monosaccharides interconnected in a variety of biologically relevant linkages - isomeric properties which are invisible when the readout is mass alone.Here, we developed an LC-MS/MS-based workflow for determining glycopeptide isomer ratios. Making use of isomerically-defined glyco(peptide) standards, we observed marked differences in fragmentation behavior between isomer pairs when subjected to collision energy gradients, specifically in terms of galactosylation/sialylation branching and linkage. These behaviors were developed into component variables that allowed relative quantification of isomerism within mixtures. Importantly, at least for small peptides, the isomer quantification appeared largely independent from the peptide portion of the conjugate, allowing broad application of the method.
Activation of Ca2+phosphatase Calcineurin regulates Parkin translocation to mitochondria and mitophagy
Authors: Marchesan Elena , Nardin Alice , Mauri Sofia , Di Paola Simone , Chinellato Monica , von Stockum Sophia , Chakraborty Joy , Herkenne Stephanie , Basso Valentina , Schrepfer Emilie , Marin Oriano , Cendron Laura , Medina Diego L. , Scorrano Luca , Ziviani Elena 
Published: February 2023

AbstractSelective removal of dysfunctional mitochondria via autophagy is crucial for the maintenance of cellular homeostasis. This event is initiated by the translocation of the E3 ubiquitin ligase Parkin to damaged mitochondria, and it requires the Serine/Threonine-protein kinase PINK1. In a coordinated set of events, PINK1 operates upstream of Parkin in a linear pathway that leads to the phosphorylation of Parkin, Ubiquitin, and Parkin mitochondrial substrates, to promote ubiquitination of outer mitochondrial membrane proteins. Ubiquitin decorated mitochondria are selectively recruiting autophagy receptors,which are required to terminate the organelle via autophagy. In this work we show a previously uncharacterized molecular pathway that correlates the activation of the Ca2+-dependent phosphatase Calcineurin to Parkin-dependent mitophagy. Calcineurin downregulation or genetic inhibition prevents Parkin translocation to CCCP-treated mitochondria, and impairs stress-induced mitophagy, whereas Calcineurin activation promotes Parkin mitochondrial recruitment and basal mitophagy. Calcineurin interacts with Parkin, and promotes Parkin translocation in the absence of PINK1, but requires PINK1 expression to execute mitophagy in MEF cells. Genetic activation of Calcineurinin vivoboosts basal mitophagy in neurons, and corrects locomotor dysfunction and mitochondrial respiratory defects of aDrosophilamodel of impaired mitochondrial functions.Our study identifies Calcineurin as a novel key player in the regulation of Parkin translocation and mitophagy.
Drug-induced eRF1 degradation promotes readthrough and reveals a new branch of ribosome quality control
Authors: Gurzeler Lukas-Adrian , Link Marion , Ibig Yvonne , Schmidt Isabel , Galuba Olaf , Schoenbett Julian , Gasser-Didierlaurant Christelle , Parker Christian N. , Mao Xiaohong , Bitsch Francis , Schirle Markus , Couttet Philipp , Sigoillot Frederic , Ziegelmüller Jana , Uldry Anne-Christine , Schmiedeberg Niko , Mühlemann Oliver , Reinhardt Jürgen 
Published: February 2023

SummarySuppression of premature termination codons (PTC) by translational readthrough is a promising strategy to treat a wide variety of severe genetic diseases caused by nonsense mutations. Here, we present two novel and potent readthrough promoters – NVS1.1 and NVS2.1 – that restore substantial levels of functional full-length CFTR and IDUA proteins in disease models for cystic fibrosis and Hurler syndrome, respectively. In contrast to other readthrough promoters that affect stop codon decoding, the NVS compounds stimulate PTC suppression by triggering rapid proteasomal degradation of the translation termination factor eRF1. Our results show that this occurs by trapping eRF1 in the terminating ribosome, causing ribosome stalls and subsequent ribosome collisions, activating a novel branch of the ribosome-associated quality control (RQC) network that involves the translational stress sensor GCN1 and the catalytic activity of the E3 ubiquitin ligases RNF14 and RNF25.
An Ancestral Balanced Inversion Polymorphism Confers Global Adaptation
Authors: Kapun Martin , Mitchell Esra Durmaz , Kawecki Tadeusz J. , Schmidt Paul , Flatt Thomas 
Published: February 2023

AbstractSince the pioneering work of Dobzhansky in the 1930s and 1940s, many chromosomal inversions have been identified but how they contribute to adaptation remains poorly understood. InDrosophila melanogaster, the widespread inversion polymorphismIn(3R)Payneunderpins latitudinal clines in fitness traits on multiple continents. Here, we use single-individual whole-genome sequencing, transcriptomics and published sequencing data to study the population genomics of this inversion on four continents: in its ancestral African range and in derived populations in Europe, North America, and Australia. Our results confirm that this inversion originated in sub-Saharan Africa and subsequently became cosmopolitan; we observe marked monophyletic divergence of inverted and non-inverted karyotypes, with some substructure among inverted chromosomes between continents. Despite divergent evolution of this inversion since its out-of-Africa migration, derived non-African populations exhibit similar patterns of long-range linkage disequilibrium between the inversion breakpoints and major peaks of divergence in its center, consistent with balancing selection and suggesting that the inversion harbors alleles that are maintained by selection on several continents. Using RNA-seq we identify overlap between inversion-linked SNPs and loci that are differentially expressed between inverted and non-inverted chromosomes. Expression levels are higher for inverted chromosomes at low temperature, suggesting loss of buffering or compensatory plasticity and consistent with higher inversion frequency in warm climates. Our results suggest that this ancestrally tropical balanced polymorphism spread around the world and became latitudinally assorted along similar but independent climatic gradients, always being frequent in subtropical/tropical areas but rare or absent in temperate climates.
Remodeling of the Ribosomal Quality Control and Protein Translation by a Viral Ubiquitin Deconjugase
Authors: Liu Jiangnan , Nagy Noemi , Aguilar-Alonso Francisco , Esteves Francisco , Ayala-Torres Carlos , Xu Shanshan , Masucci Maria G. 
Published: February 2023

SUMMARYThe strategies adopted by viruses to reprogram the protein translation and quality control machineries to promote infection are poorly understood. Here, we discovered that the viral ubiquitin deconjugase (vDUB) encoded in the large tegument protein of Epstein- Barr virus (EBV) regulates ribosomal stress responses. The vDUB participates in protein complexes that include the ubiquitin ligases ZNF598 and LTN1 and the UFM1 ligase UFL1. Upon ribosomal stalling, the vDUB counteracts the ubiquitination of 40S ribosome subunits, inhibits the degradation of translation-stalled polypeptides by the proteasome, and prevents UFMylation of the 60S particle, which impairs the ER-phagy- dependent clearance of stalled products. Inhibition of the ribosome quality control activates a GCN2-dependent integrated stress response that decreases global protein translation while promoting the readthrough of stall-inducing mRNAs. The vDUB enhances viral mRNAs translation and virus release during productive infection, pointing to a pivotal role in cell reprogramming that enables virus production and underlies the pathogenesis of EBV-associated cancers and autoimmune diseases.GRAPHIC SUMMARY
A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways inPlasmodium vivaxHypnozoites
Authors: Maher S. P. , Bakowski M. A. , Vantaux A. , Flannery E. L. , Andolina C. , Gupta M. , Antonova-Koch Y. , Argomaniz M. , Cabrera-Mora M. , Campo B. , Chao A. T. , Chatterjee A. K. , Cheng W. T. , Chuenchob E. , Cooper C. A. , Cottier K. , Galinski M. R. , Harupa-Chung A. , Ji H. , Joseph S. B. , Lenz T. , Lonardi S. , Matheson J. , Mikolajczak S. A. , Moeller T. , Orban A. , Padín-Irizarry V. , Pan K. , Péneau J. , Prudhomme J. , Roesch C. , Ruberto A. A. , Sabnis S. S. , Saney C. L. , Sattabongkot J. , Sereshki S. , Suriyakan S. , Ubalee R. , Wang Y. , Wasisakun P. , Yin J. , Popovici J. , McNamara C. W. , Joyner C. J. , Nosten F. , Witkowski B. , Le Roch K. G. , Kyle D. E. 
Published: February 2023

AbstractRadical cure ofPlasmodium vivaxmalaria must include elimination of quiescent ‘hypnozoite’ forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets for hypnozoites, we screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library and a collection of epigenetic inhibitors againstP. vivaxliver stages. From both libraries, we identified inhibitors targeting epigenetics pathways as selectively active againstP. vivaxandP. cynomolgihypnozoites. These include DNA methyltransferase (DNMT) inhibitors as well as several inhibitors targeting histone post-translational modifications. Immunofluorescence staining ofPlasmodiumliver forms showed strong nuclear 5-methylcystosine signal, indicating liver stage parasite DNA is methylated. Using bisulfite sequencing, we mapped genomic DNA methylation in sporozoites, revealing DNA methylation signals in most coding genes. We also demonstrated that methylation level in proximal promoter regions as well as in the first exon of the genes may affect, at least partially, gene expression inP. vivax. The importance of selective inhibitors targeting epigenetic features on hypnozoites was validated using MMV019721, an acetyl-CoA synthetase inhibitor that affects histone acetylation and was previously reported as active againstP. falciparumblood stages. In summary, our data indicate that several epigenetic mechanisms are likely modulating hypnozoite formation or persistence and provide an avenue for the discovery and development of improved radical cure antimalarials.One-Sentence SummaryDrug repurposing screens reveal several epigenetic inhibitors as active againstP. vivaxhypnozoites demonstrating that epigenetic pathways play a central role in hypnozoite quiescence.
Central bank digital currency and bank earnings management using loan loss provisions
Authors: Ozili Peterson K. 
Published: February 2023

Purpose
This paper aims to analyse the role of central bank digital currency (CBDC) in bank earnings management and focus on how CBDC activity might influence banks to engage in accrual earnings management using loan loss provisions (LLPs) and the implications for earnings quality.

Design/methodology/approach
The paper used conceptual discourse analysis to explain the role of CBDC in bank earnings management.

Findings
Banks will use accruals, such as LLPs, to manage earnings when CBDC-induced bank disintermediation leads to a reduction in bank deposits, a reduction in bank lending and a likely reduction in reported earnings. Bank managers will mitigate the reduction in reported earnings by lowering discretionary LLPs to increase reported earnings.

Originality/value
The recent emergence of CBDC in the digital currency universe has led to increased research interest on the role of CBDC in corporations and society. This study contributes to the literature by focusing on banks, and examining the effect of CBDC on bank earnings management.