bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness Versus Lineage Output inDnmt3a-Mutant Clonal Hematopoiesis
Authors: SanMiguel Jennifer M. , Eudy Elizabeth , Loberg Matthew A. , Young Kira A. , Mistry Jayna J. , Schwartz Logan S. , Stearns Tim , Challen Grant A. , Trowbridge Jennifer J. 
Published: July 2022

AbstractClonal hematopoiesis resulting from enhanced fitness of mutant hematopoietic stem cells (HSCs) associates with both favorable and unfavorable health outcomes related to the types of mature mutant blood cells produced, but how this lineage output is regulated is unclear. Using a mouse model of a clonal hematopoiesis-associated mutation,DNMT3AR882/+(Dnmt3aR878H/+), we found that aging-induced TNFα signaling promoted the selective advantage of mutant HSCs as well as stimulated mutant B lymphoid cell production. Genetic loss of TNFα receptor TNFR1 impaired mutant HSC fitness without altering lineage output, while loss of TNFR2 reduced lymphoid cell production and favored myeloid cell production from mutant HSCs without altering overall fitness. These results support a model where clone size and mature blood lineage production can be independently controlled to harness potential beneficial aspects of clonal hematopoiesis.Statement of SignificanceThrough identification and dissection of TNFα signaling as a key driver of murineDnmt3a-mutant hematopoiesis, we report the discovery that clone size and production of specific mature blood cell types can be independently regulated.
Oligodendrocyte-mediated Myelin Plasticity and its role in Neural Synchronization
Authors: Pajevic Sinisa , Plenz Dietmar , Basser Peter J. , Fields R. Douglas 
Published: July 2022

Temporal synchrony of signals arriving from different neurons or brain regions is essential for proper neural processing. Nevertheless, it is not well understood how such synchrony is achieved and maintained in a complex network of time-delayed neural interactions. Myelin plasticity has been suggested as an efficient mechanism for controlling timing in brain communications through adaptive changes of axonal conduction velocity and consequently conduction time delays, or latencies; however, local rules and feedback mechanisms that oligodendrocytes (OL) use to achieve synchronization are not known. We propose a mathematical model of oligodendrocyte-mediated myelin plasticity (OMP) in which OL play an active role in providing such feedback. This is achieved without using arrival times at the synapse or modulatory signaling from astrocytes; instead, it relies on the presence of global and transient OL responses to local action potentials in the axons they myelinate. While inspired by OL morphology, we provide the theoretical underpinnings that motivated the model and explore its performance for a wide range of its parameters. Our results indicate that when the characteristic time of OL’s spike responses is between 10 and 40 ms and the firing rates in individual axons are relatively low (⪅ 10 Hz), the OMP model efficiently synchronizes correlated and time-locked signals while latencies in axons carrying independent signals are unaffected. This suggests a novel form of selective synchronization in the CNS in which oligodendrocytes play an active role by modulating the conduction delays of correlated spike trains as they traverse to their targets.Significance StatementSynchronization of signals arriving from different neurons or brain regions is of great importance for proper brain function. In vertebrates, myelination provides an efficient way to achieve this by adjusting the conduction velocity and consequently the conduction delays. It is increasingly evident that myelination is an adaptive process and involved in learning; however, the local rules and the feedback that guide oligodendrocytes towards achieving desired delays are not known. Here we propose a simple and biologically plausible model of myelin plasticity in which oligodendrocytes play an active role in providing the needed feedback. We use theoretical arguments, mathematical modeling and computer simulations to show its robust synchronization capabilities which enable efficient communication between the brain regions.
Iron-catalyzed antagonism between NO and H2O2 / HOCl causes mutual exclusivity of HOCl- and NO/peroxynitrite-mediated apoptosis-inducing signaling
Authors: Bauer Georg 
Published: July 2022

AbstractMembrane-associated NADPH oxidase of malignant cells drives intercellular apoptosis-inducing HOCl- and NO/peroxynitrite signaling. Cells from late stages of oncogenesis, i. e. bona fide tumor cells, interfere with these signaling pathways through expression of membrane-associated catalase. Transformed cells and tumor cells with inhibited catalase show mutual exclusivity of apoptosis-inducing NO/peroxynitrite and HOCl signaling. H2O2 is the substrate for HOCl synthesis by DUOX-coded peroxidase. However, at high concentrations of H2O2, HOCl signaling is abrogated through the reaction between excess H2O2 and HOCl. Experimental increase in the NO concentration through addition of NO donors, induction of NO synthase (NOS), addition or the NOS substrate arginine, or inhibition of NO dioxygenase(NOD) leads to the inhibition of HOCl signaling, but also to abrogation of H2O2-mediated interference with HOCl signaling. Vice versa, an increase in extracellular H2O2 through increasing the cell density, gamma irradiation or addition of glucose oxidase inhibits NO/peroxynitrite signaling. These mutual reactions between NO and H2O2/HOCl are catalyzed by an iron-mediated reaction cycle, which allows consumption of NO by H2O2/HOCl and vice versa. These reactions explain the preferences of tumor cell lines for NO/peroxynitrite or HOCl signaling after inhibition of their protective catalase, as well as the differential expression of these pathways dependent on the degree of catalase inhibition. The understanding of these reactions allows to rationally modulate quality and strength of ROS/RNS-dependent apoptosis-inducing signaling pathways of malignant cells. The knowledge about these reactions should allow to optimize strategies for tumor therapy that are based on reactivation of intercellular ROS/RNS-dependent apoptosis-inducing signaling of tumor cells.Graphical abstractHighlights•NADPH oxidase and peroxidase drive apoptosis-inducing HOCl signaling•NADPH oxidase and NO synthase drive apoptosis-inducing NO/peroxynitrite signaling•H2O2 establishes and interferes with HOCl signaling, dependent on its concentration•NO inhibits HOCl signaling and abrogates H2O2-dependent inhibition of HOCl signaling•H2O2 interferes with NO/peroxnitrite signaling•Mutual interactions of NO and H2O2 are catalysed by an iron-mediated reaction cycle
Directed growth and fusion of membrane-wall microdomains requires CASP-mediated inhibition and displacement of secretory foci
Authors: Barbosa ICR , De Bellis D , Flückiger I , Bellani E , Grangé-Guerment M , Hématy K , Geldner N 
Published: July 2022

SummaryCasparian strips (CS), the main extracellular diffusion barrier in plant roots, are precisely localized cell wall lignin-impregnations, contrasting animal tight-junctions. The CS membrane domain (CSD) proteins 1-5 (CASP1-5) define and accumulate at the CS associated membrane domains displaying matrix adhesion and protein exclusion. A full CASP knock-out (caspQ) now reveals that CASPs are not needed for localization of lignification or lignin-polymerizing enzymes, since correctly aligned spots still form in the mutant. Ultra-structurally, however, these spots appear as highly disorganized secretory foci, with neither exclusion zone nor membrane attachment and excessive cell wall growth. Biotin proximity labelling identifies RabA-GTPases as potential CASP-interactors. We confirm their localisation and function at the CSD, similar to exocyst subunits, known Rab effectors. Our work reveals that CASPs enforce displacement of initial secretory foci through exclusion of vesicle tethering factors, thereby ensuring rapid fusion of microdomains and effective sealing of the cell wall space.
Repurposing azithromycin in combination with last-line fosfomycin, colistin and tigecycline against Multi-Drug ResistantKlebsiella pneumoniae
Authors: Gómara-Lomero Marta , López-Calleja Ana Isabel , Rezusta Antonio , Aínsa José A. , Ramón-García Santiago 
Published: July 2022

AbstractBackgroundNew therapeutical strategies are urgently needed against multidrug-resistant (MDR) Enterobacterales. Azithromycin is a widely prescribed antibiotic with additional immunomodulatory properties, but traditionally underused for the treatment of enterobacterial infections. We previously identified azithromycin as a potent enhancer of colistin, fosfomycin and tigecycline againstKlebsiella pneumoniaeATCC 13883.ObjectivesThe aim of this work was to evaluate the antibacterialin vitroactivity of azithromycin-based combinations with last-line antibiotics against an expanded panel of MDR/XDRK. pneumoniaeisolates.MethodsTime-kill assays of azithromycin alone and in pair-wise combinations with fosfomycin, colistin and tigecycline were performed against a collection of 12 MDR/XDRK. pneumoniaeisolates. Synergistic and bactericidal activities of azithromycin-based combinations were analyzed after 8, 24 and 48 hours of treatment, and compared with antimicrobial combinations frequently used in the clinic for the treatment of MDR Enterobacterales.ResultsSynergistic interactions were detected in 100% (12/12) for azithromycin/fosfomycin, 58.3% (7/12) for azithromycin/colistin and 75% (9/12) for azithromycin/tigecycline of the strains, showing potent killing activities. Clinical combinations currently used in the clinic showed synergy in 41.6% (5/12) for meropenem/ertapenem, 33.33% (4/12) for meropenem/colistin, 75% (9/12) for fosfomycin/colistin and 66.6% (8/12) for fosfomycin/tigecycline of the strains, with lower bactericidal efficacy.ConclusionsNovel azithromycin-based combinations with last-line MDR/XDRK. pneumoniaeantibiotics were identified showingin vitrocapacity to eradicate MDR/XDRK. pneumoniae. Our results provide anin vitrobasis supporting azithromycin used in combinatorial treatment for MDR-related infections.
Reciprocal Best Structure Hits: Using AlphaFold models to discover distant homologues
Authors: Monzon Vivian , Paysan-Lafosse Typhaine , Wood Valerie , Bateman Alex 
Published: July 2022

1AbstractThe conventional methods to detect homologous protein pairs use the comparison of protein sequences. But the sequences of two homologous proteins may diverge significantly and consequently may be undetectable by standard approaches. The release of the AlphaFold 2.0 software enables the prediction of highly accurate protein structures and opens many opportunities to advance our understanding of protein functions, including the detection of homologous protein structure pairs. In this proof-of-concept work, we search for the closest homologous protein pairs using the structure models of five model organisms from the AlphaFold database. We compare the results with homologous protein pairs detected by their sequence similarity and show that the structural matching approach finds a similar set of results. Additionally, we detect potential novel homologues solely with the structural matching approach, which can help to understand the function of uncharacterised proteins and make previously overlooked connections between well-characterised proteins. We also observe limitations of our implementation of the structure based approach, particularly when handling highly disordered proteins or short protein structures. Our work shows that high accuracy protein structure models can be used to discover homologous protein pairs, and we expose areas for improvement of this structural matching approach.
Gyne production is regulated by the brood in a social bee (Bombus impatiens)
Authors: Santos Priscila K. F. , Murray Cameron S. , Amsalem Etya 
Published: July 2022

AbstractSexual production in social insects marks the peak of colony development, yet the mechanisms regulating it remain unclear. We investigated the role of brood in colony development and sexual production inBombus impatiens. While larvae are known to reduce worker egg-laying and enhance the queen’s reproductive inhibition, these effects were previously tested only in small groups. We manipulated brood size in full-size, young colonies by doubling or removing brood and monitored development. Colonies with doubled brood produced significantly more gynes, independent of colony size, while reduced-brood colonies showed a slight, non-significant increase in male production. Worker reproduction was delayed in double-brood colonies, with no change in aggression. These findings suggest brood strongly influences colony development, possibly acting as an extended phenotype of the queen or shaping worker behaviour. Understanding brood dynamics may be key to unravelling female caste determination in social insects.
Structural basis of the mycobacterial stress-response RNA polymerase auto-inhibition via oligomerization
Authors: Morichaud Zakia , Trapani Stefano , Vishwakarma Rishi , Chaloin Laurent , Lionne Corinne , Lai-Kee-Him Joséphine , Bron Patrick , Brodolin Konstantin 
Published: July 2022

SUMMARYSelf-assembly of macromolecules into higher-order symmetric structures is fundamental for the regulation of biological processes. Higher-order symmetric structure self-assembly by the gene expression machinery, such as bacterial DNA-dependent RNA polymerase (RNAP), has never been reported before. Here, we show that the stress-response σB factor from the human pathogen, Mycobacterium tuberculosis, induces the RNAP holoenzyme oligomerization into a supramolecular complex composed of eight RNAP units. Cryo-electron microscopy revealed a pseudo-symmetric structure of the RNAP octamer in which RNAP protomers are captured in an auto-inhibited state and display an open-clamp conformation. The structure shows that σB is sequestered by the RNAP flap and clamp domains. The transcriptional activator RbpA prevented octamer formation by promoting the initiation-competent RNAP conformation. Our results revealed that nonconserved region of σ is an allosteric controller of transcription initiation and demonstrated how basal transcription factors can regulate gene expression by modulating the RNAP holoenzyme assembly and hibernation.
Graft of cardiac progenitors in a pig model of right ventricular failure triggers myocardial epimorphosis, regeneration and protection of function
Authors: Lambert V , Deleris A , Tibourtine F , Fouilloux V , Martin A , Bridge P , Aries E , Benoist D , Pucéat M 
Published: July 2022

The failure of diseased adult heart to regenerate is a major burden to our societies. Besides patients with ischemia and left ventricular dysfunction, progress in pediatric surgery to repair cardiac malformations has led to a growing population of now adult congenital heart diseases patients with right ventricular failure. In the absence of any efficient pharmacological therapy for these patients, cell therapy has turned out to be the only option to regenerate the RV myocardium.In this study, we demonstrate that the adult pig with RV failure, a model of repaired tetralogy of Fallot, has the ability of regenerative epimorphosis.Human embryonic stem cell-derived cardiac Nkx2.5+ progenitor cells were seeded in a collagen based patch to cover the whole pig failing RV. We report that these cells migrate within the myocardium while reversing the interstitial fibrosis. They then engraft and fully differentiate into fetal-like human myocytes within the myocardium. The graft triggers activation of macrophages and the reprogramming of surrounding pig myocytes into Oct4+/Nanog-blastemal-like cells. The reprogrammed myocytes re-differentiate and proliferate around human myocytes. Altogether, our findings reveal that mammalian hearts have the ability to undergo epimorphosis, the major process of endogenous regeneration that leads to a recovery of their contractile function.
Synthesis, chiral crystal structure, and magnetic properties of Ba3Ga2O5Cl2
Authors: Rine Jeremy , Yang Yongqi , Shu Zhixue , Zhao Jianda , Xie Weiwei , Kong Tai 
Published: July 2022

A new compound, Ba3Ga2O5Cl2, isostructural with Ba3Fe2O5Cl2, was synthesized by solid-state reaction in air. Through single-crystal and powder X-ray diffraction analysis, the crystal structure was determined to be cubic with chiral space group I213 and unit-cell parameter a = 9.928 (1) Å. The Ga3+ ions in Ba3Ga2O5Cl2 are coordinated by O atoms and form GaO4 tetrahedra. Ten neighboring GaO4 tetrahedra are further bridged through corner sharing and rotation along the body diagonal, producing the chiral structure. Magnetization measurements indicate temperature-independent diamagnetic behavior, which is qualitatively consistent with core diamagnetism from all the constituent elements.
A literature review on users' behavioral intention toward chatbots' adoption
Authors: Gatzioufa Paraskevi , Saprikis Vaggelis 
Published: July 2022

PurposeDespite the fact that chatbots have been largely adopted for the last few years, a comprehensive literature review research focusing on the intention of individuals to adopt chatbots is rather scarce. In this respect, the present paper attempts a literature review investigation of empirical studies focused on the specific issue in nine scientific databases during 2017-2021. Specifically, it aims to classify extant empirical studies which focus on the context of individuals' adoption intention toward chatbots.Design/methodology/approachThe research is based on PRISMA methodology, which revealed a total of 39 empirical studies examining users' intention to adopt and utilize chatbots.FindingsAfter a thorough investigation, distinct categorization criteria emerged, such as research field, applied theoretical models, research types, methods and statistical measures, factors affecting intention to adopt and further use chatbots, the countries/continents where these surveys took place as well as relevant research citations and year of publication. In addition, the paper highlights research gaps in the examined issue and proposes future research directions in such a promising information technology solution.Originality/valueAs far as the authors are concerned, there has not been any other comprehensive literature review research to focus on examining previous empirical studies of users' intentions to adopt and use chatbots on the aforementioned period. According to the authors' knowledge, the present paper is the first attempt in the field which demonstrates broad literature review data of relevant empirical studies.
Is consumers' willingness to pay premium for agricultural brand labels sustainable?: evidence from Chinese consumers' random n-price auction experiment
Authors: Bo Le , Yang Xiaoli 
Published: July 2022

PurposeConsumers' willingness to pay premium (WTPP) for two different types of agricultural brand labels (enterprise and regional), are evaluated through a non-hypothetical Random n-price auction experiment during the online purchase of fresh agricultural products. The purpose of this paper is to evaluate the two WTPP, compare their differences, and explore their sustainability.Design/methodology/approachData were collected in July–August 2020 from a sample of 310 consumers in Liaoning Province, China. A nonhypothetical random n-price auction experiment was implemented in a simulated online shopping environment.FindingsThe results show that WTPP exists, and WTPP level of regional brand labels is higher than that of enterprise brand labels. Consumers' WTPP is sustainable. Consumers with low WTPP for enterprise brand labels and consumers with high WTPP for regional brand labels have stronger willingness to repurchase.Practical implicationsThe results have direct practical implications for developing brand agriculture and encouraging “brand consumption”. The results can provide theoretical reference for policymakers, enlightenment for the development and effective dissemination of agricultural brand labels and important information to e-retailers on how to sale agricultural products with agricultural brand labels.Originality/valueTo the best of the authors' knowledge, no previous study has related WTPP and its sustainability for agricultural brand labels in China. We try to fill a gap in literature on consumers' WTPP for agricultural brand labels. And the authors explore the sustainability of WTPP by analyzing the impact of WTPP on repurchase intention and recommendation intention respectively.
Total expenses for managerial remuneration in foreign manufacturing subsidiaries during the COVID-19 pandemic: a pilot exploration of applied policies
Authors: Gurkov Igor 
Published: July 2022

PurposeThis study aimed to reveal the policies applied to determine the total expenses for managerial remuneration in manufacturing subsidiaries during the COVID-19 pandemic.Design/methodology/approachThe author analyzed the annual financial reports of Russian manufacturing subsidiaries containing data on managerial remuneration and compared the dynamics of annual revenues and the amount of annual managerial remuneration.FindingsThe author identified four types of policies regarding the total amount of managerial remuneration. In a minority of cases, when revenues decreased, the share of the total amount of managerial remuneration in total revenues also decreased. The author also observed “payment for efforts”; although revenues decreased in 2020, the share of the total amount of managerial remuneration in total revenues increased. In 17% of cases, when revenue increased, the share of the total amount of managerial remuneration in revenue also increased. Finally, in 50% of cases, the COVID-19 pandemic served as a pretext to generate savings from the reduction in the total amount of managerial remuneration despite the increase in revenues.Originality/valueThis is the first study to use real financial reports to evaluate the dynamics of the total amount and share of managerial remuneration in revenue during a crisis.
Decomposing the role of mobility restrictions in controlling COVID-19 outcomes: a regional level study of the Philippines
Authors: Gaduena Ammielou , Caboverde Christopher Ed , Flaminiano John Paul , Romero Regina Yvette 
Published: July 2022

PurposeThis paper aims to explore empirically the interactions between the coronavirus disease 2019 (COVID-19) pandemic, economic mobility and containment policy to test the effectiveness of mobility restrictions in controlling the spread of the disease.Design/methodology/approachThis study used weekly regional data for the 17 Philippine regions and estimated the effect of shocks using a panel vector autoregression (VAR) model.FindingsThe authors conclude that COVID-19 deaths and incidence primarily respond to shocks that affect the lethality and transmissibility of the disease, and mobility restrictions and strict quarantine levels do not seem to have any impact on these outcomes. The movement of people during this pandemic period, on the other hand, seems to respond more to economic factors and government restrictions and less to the presence of and the characteristics of the disease.Originality/valueSince the pandemic is a public bad, community cooperation is a must to address it. Clear government messaging that dispels doubts on the safety of the newly developed vaccines and that encourages public acceptance and trust might be a better nudge compared to a heavy-handed and threatening approach.