bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRBP regulates poly(I:C)-mediated apoptotic pathway by modulating miRNA biogenesis
Authors: Azuma Shota , Nakano Yuko , Takahashi Tomoko , Onomoto Koji , Haraguchi Takeshi , Suzuki Yutaka , Iba Hideo , Yoneyama Mitsutoshi , Asano Yoshimasa , Ui-Tei Kumiko 
Published: May 2024

ABSTRACTInterferon (IFN) response is usually triggered by the invasion of viral RNAs, and is known to suppress RNA silencing triggered by microRNAs (miRNAs). However, the detailed mechanism regulating RNA silencing during IFN response has not been elucidated. We previously reported that a virus sensor protein, LGP2, which is an upregulated protein during IFN response, interacts with an RNA-binding protein, TRBP. Since TRBP is an RNA-binding protein which enhances miRNA biogenesis in collaboration with Dicer, the interaction of TRBP with LGP2 inhibits the interaction with Dicer and suppresses the TRBP-mediated miRNA biogenesis. During Sendai virus infection, we found that the inhibition of miRNA maturation caused by TRBP depletion resulted in the induction of apoptosis. However, the global gene expression network regulated by miRNAs during viral infection is not understood. In this study, we analyzed comprehensive data from RNA-sequencing and small RNA-sequencing during the antiviral response induced by poly(I:C) transfection, and investigated how TRBP regulates expression profiles of miRNAs and the downstream mRNAs. A group of miRNAs, including miRNAs preferably bind to TRBP, were downregulated by poly(I:C) transfection. Although about 60 % of miRNAs were situated in the introns of their host genes, the expression levels of mature miRNAs were not correlated with those of host genes. Therefore, the downregulation of the expression levels of mature miRNAs was considered to be not caused by transcriptional inhibition of host genes but by the inhibition of TRBP-mediated miRNA processing. Target prediction analysis suggested that the downregulated miRNAs in the presence of TRBP but not in the absence of TRBP mainly targeted transcription factors. Furthermore, these transcription factors were included in the regulators of apoptosis- and cell cycle-related factors. Some of these regulators were also predicted to be the direct targets of downregulated miRNAs in the presence of TRBP. Thus, it was revealed that the downregulation of miRNAs in the presence of TRBP regulates the expression of apoptosis- and cell cycle-related genes either directly or indirectly through adjusting the expression levels of transcription factors. These results suggest that TRBP has a pivotal role in the determination of cell fates during viral infection regulating the miRNA-mRNA regulatory networks through modifying miRNA biogenesis.
Quantifying uncertainty in RNA velocity
Authors: Zhang Huizi , Bochkina Natalia , Wade Sara 
Published: May 2024

AbstractThe concept of RNA velocity has made it possible to extract dynamic information from single-cell RNA sequencing data snapshots, attracting considerable attention and inspiring various extensions. Nonetheless, existing approaches lack uncertainty quantification and many adopt unrealistic assumptions or employ complex black-box models that are difficult to interpret. In this paper, we present a Bayesian hierarchical model to estimate RNA velocity, which leverages a time-dependent transcription rate and non-trivial initial conditions, allowing for well-calibrated uncertainty quantification. The proposed method is validated in a comprehensive simulation study that covers various scenarios, and benchmarked against a widely embraced and commonly recognized approach for RNA velocity on single-cell RNA sequencing data from mouse embryonic stem cells. We demonstrate that our model surpasses this widely used, state-of-the-art method, offering enhanced interpretation of cell velocity and cell orders. Additionally, it supports the estimation of a unified gene-shared latent time, providing a valuable resource for downstream analysis.
Neural Processing of Naturalistic Audiovisual Events in Space and Time
Authors: Hu Yu , Mohsenzadeh Yalda 
Published: May 2024

AbstractOur brain seamlessly integrates distinct sensory information to form a coherent percept. However, when real-world audiovisual events are perceived, the specific brain regions and timings for processing different levels of information remain less investigated. To address that, we curated naturalistic videos and recorded fMRI and EEG data when participants viewed videos with accompanying sounds. Our findings reveal early asymmetrical cross-modal interaction, with acoustic information represented in both early visual and auditory regions, while visual information only identified in visual cortices. The visual and auditory features were processed with similar onset but different temporal dynamics. High-level categorical and semantic information emerged in multi-modal association areas later in time, indicating late cross-modal integration and its distinct role in converging conceptual information. Comparing neural representations to a two-branch deep neural network model highlighted the necessity of early fusion to build a biologically plausible model of audiovisual perception. With EEG-fMRI fusion, we provided a spatiotemporally resolved account of neural activity during the processing of naturalistic audiovisual stimuli.
Amyloid beta glycation leads to 1 neuronal mitochondrial dysfunction and Alzheimer’s pathogenesis through VDAC1-dependent mtDNA efflux
Authors: Akhter Firoz , Akhter Asma , Schiff Hillary , Maffei Arianna , Zhu Xiongwei , Douglas Justin , Zhao Zhen , Zhu Donghui 
Published: May 2024

AbstractAmyloid beta (Aβ), a stable protein, undergoes posttranslational glycation, forming glycated Aβ (gAβ), an advanced glycation end product (AGE) observed in Alzheimer’s disease (AD), yet the pathological role of gAβ remains understudied. This work explores gAβ’s role in inducing neuronal mitochondrial DNA (mtDNA) efflux in a VDAC1-dependent manner and in activating the innate immune cGAS-STING pathway in AD. Findings demonstrate cGAS-mtDNA binding induced by gAβ in neuro-cytoplasm, along with cGAS-STING activation in aged AD mice and human AD brains. Knockdown of RAGE, cGAS, or STING protects APP mice from mitochondrial dysfunction and AD-like pathology, as does inhibiting VDAC1. Moreover, RAGE inhibition in APP knock-in mice, coupled with spatially enhanced resolution omics-sequencing, confirms downregulation of innate immune responses and disease-associated genes in AD. Therefore, this study identifies a crucial link between gAβ and innate immunity, indicating therapeutic targeting of VDAC1, RAGE, or cGAS-STING may enhance resilience against gAβ-related pathological insults in AD.
Melanopsin ganglion cells in the mouse retina independently evoke pupillary light reflex
Authors: Bohl Jeremy Matthew , Hassan Abdul Rhman , Sharpe Zachary J. , Kola Megi , Ayub Mahnoor , Pandey Yamini , Shehu Angela , Ichinose Tomomi 
Published: May 2024

AbstractPurposeThe pupillary light reflex (PLR) is crucial for protecting the retina from bright light. The intrinsic photosensitive ganglion cells (ipRGCs) in the retina mediate the PLR, which directly sense light and receive inputs from rod/cone photoreceptors. Previous work used genetic knockout mice to reveal that rod/cone photoreceptors drive transient constriction, and ipRGCs drive the sustained component. We acutely ablated photoreceptors by a chemical injection to examine the role of rod and cone photoreceptors in PLR.MethodsPLR and the multiple electrode array (MEA) recording were conducted with C57BL6/J (wildtype: WT) and Cnga3-/-; Gnat1-/-(rod/cone dysfunctional) mice. n-Nitroso-n-methylurea (MNU) was applied to C57 mice by intraperitoneal injection, and PLR was conducted after 5-7 days of injection. Three different light levels (mesopic, low photopic, and high photopic) were tested. Immunohistochemistry was conducted using the anti-Gnat1 and anti-melanopsin antibodies with DAPI.ResultsPLR was induced by all light levels we tested, and the level of constriction increased as the light level increased. After the MNU injection, PLR was not induced at mesopic light stimulus, but was fully induced by high light. The level of PLR was identical between WT and MNU mice, suggesting that ipRGCs fully contributed to the PLR at this light level. Immunohistochemistry revealed that photoreceptors were ablated by the MNU injection, but ipRGCs were preserved. The MEA recording revealed that a population of ipRGCs generated fast and robust spikes in MNU-injected retinal tissues inex vivo.ConclusionsContrary to previous observations, our results demonstrate that ipRGCs are the major contributor to the PLR induced by high light.
Beyond the Triple Helix: Exploration of the Hierarchical Assembly Space of Collagen-like Peptides
Authors: Yu Le Tracy , Kreutzberger Mark A. B. , Hancu Maria C. , Bui Thi H. , Farsheed Adam C. , Egelman Edward H. , Hartgerink Jeffrey D. 
Published: May 2024

AbstractThede novodesign of self-assembling peptides has garnered significant attention in scientific research. While alpha-helical assemblies have been extensively studied, exploration of polyproline type II (PPII) helices, such as those found in collagen, remains relatively limited. In this study, we focused on understanding the sequence-structure relationship in hierarchical assemblies of collagen-like peptides, using defense collagen SP-A as a model. By dissecting the sequence derived from SP-A and synthesizing short collagen-like peptides, we successfully constructed a discrete bundle of hollow triple helices. Mutation studies pinpointed amino acid sequences, including hydrophobic and charged residues that are critical for oligomer formation. These insights guided thede novodesign of collagen-like peptides, resulting in the formation of diverse quaternary structures, including discrete and heterogenous bundled oligomers, 2D nanosheets, and pH-responsive nanoribbons. Our study represents a significant advancement in the understanding and harnessing of collagen higher-order assemblies beyond the triple helix.
Dicarboxylic acids synergize with yeast and human Hsp60/10 systems to mimic GroEL/ES
Authors: Gautam Deepika , Aaquib Mohammad , Kochar Manisha , Chakraborty Kausik 
Published: May 2024

AbstractGroEL/ES has been the archetype to understand the function of the class I chaperonins (Hsp60/10 systems). While very similar in structure, the human or yeast mitochondrial one has diminished negative charge density in the central cavity. These chaperones had also lost their ability to assist a substrate ofE.coliGroEL/ES. Here, we show that the eukaryotic Hsp60/10 systems can synergize with dicarboxylic acids in vitro at the physiological concentration of these metabolites to mimic the activity ofE. coliGroEL/ES. Combining these Hsp60/10s and metabolites effectively alters the folding landscape like GroEL/ES; this is specific for the eukaryotic chaperonins and not the prokaryotic homologs with less negatively charged cavities. Thus, we identify a potential cooperation between molecular and chemical chaperones that may have important physiological implications linking metabolism to proteostasis.
A new target of multiple lysine methylation in bacteria
Authors: Inoue Shori , Yoshimoto Shogo , Hori Katsutoshi 
Published: May 2024

AbstractThe methylation of ε-amino groups in protein lysine residues is known to be an important posttranslational modification in eukaryotes. This modification plays a pivotal role in the regulation of diverse biological processes, including epigenetics, transcriptional control, and cellular signaling. Although less studied in prokaryotes, recent research has begun to reveal the potential role of methylation in modulating bacterial immune evasion and adherence to host cells. In this study, we analyzed the cell surface proteins of the toluene-degrading bacteriumAcinetobactersp. Tol 5 by label-free liquid chromatography‒mass spectrometry (LC‒MS) and found that the lysine residues of its trimeric autotransporter adhesin (TAA), AtaA, are methylated. Over 130 lysine residues of AtaA, consisting of 3,630 amino acids and containing 232 lysine residues, were methylated. We identified the outer membrane protein lysine methyltransferase (OM PKMT) of Tol 5, KmtA, which specifically methylates the lysine residues of AtaA. In the KmtA-deficient mutant, most lysine methylations on AtaA were absent, indicating that KmtA is responsible for the methylation of multiple lysine residues throughout AtaA. Bioinformatic analysis revealed that the OM PKMT genes were widely distributed among gram-negative bacteria, including pathogens with TAAs that promote infectivity, such asBurkholderia malleiandHaemophilus influenzae. Although KmtA has sequence similarities to the OM PKMTs ofRickettsiainvolved in infectivity, KmtA-like PKMTs formed a distinct cluster from those of theRickettsiatype according to the clustering analysis, suggesting that they are new types of PKMTs. Furthermore, the deletion of Tol 5 KmtA led to an increase in AtaA on the cell surface and enhanced bacterial adhesion, resulting in slower growth.SignificanceMethylation of lysine residues is a posttranslational modification that plays diverse physiological roles in eukaryotes. In prokaryotes however, lysine methylation has been studied only in a limited number of pathogenic bacteria. In this study, we found novel lysine methylation across multiple residues of an outer membrane protein and its methyltransferase, KmtA, in a bacterium from activated sludge. KmtA, along with rickettsial outer membrane protein lysine methyltransferases, which are known to be involved in bacterial pathogenicity, exists in many species of gram-negative bacteria. This finding suggests that methylations are ubiquitous in prokaryotes and are involved in a variety of functions, offering potential strategies for controlling bacterial infections and enhancing the functions of beneficial bacteria for biotechnological applications.
Intravenous Immunization with Triple Auxotrophs ofMycobacterium tuberculosis: A novel vaccine strategy against tuberculosis
Authors: Vilchèze Catherine , Rajagopalan Saranathan , Jacobs William R. 
Published: May 2024

AbstractTuberculosis, caused byMycobacterium tuberculosis(Mtb), remains a leading infectious cause of mortality worldwide despite widespread use of the BCG vaccine and the availability of sterilizing pharmacopoeia. Recent research indicates that the intravenous administration of BCG confers sterilizing immunity againstMtbpulmonary challenge in non-human primates. However, while BCG is relatively safe, complications such as disseminated BCGosis have been observed in immunocompromised individuals. Double auxotrophic mutants ofMtblacking the ability to synthesize leucine and pantothenate are safe and sterilized in immunocompromised mice and SIV-infected Rhesus macaques. We examined how immunization with aMtbtriple auxotrophic strain, mc27902, which cannot synthesize leucine, pantothenate, and arginine, protects immunocompetent mice from a virulentMtbinfection. The route of immunization was a crucial factor for protection with mc27902 with intravenous immunization being 100 times more effective in protecting immunocompetent mice fromMtbchallenge when compared to conventional subcutaneous vaccination with BCG. To further increase the safety of the attenuated auxotroph for vaccine purposes, the type VII secretion system Esx1 responsible for BCG attenuation was deleted in mc27902. When tested by prime-boost immunization of immunocompetent mice followed by aerosol challenge with virulentMtb, mc27902 Δesx1provided similar protection to mc27902. This robust protection againstMtbinfection conferred by mc27902 and mc27902 Δesx1in a mouse model paves the way for new TB vaccine development using highly attenuated, auxotrophicMtbstrains.
Aging behavior difference between aqueous coatings and solvent coatings in sulfuric acid environment
Authors: Wang He , Li Zhiguo , Zhou Haifei , Zhou Zhengqiang , Lu Wei , Wang Pengzhen , Zhang Jiagang , Gao Jin , Yi Pan 
Published: May 2024

Purpose
This paper aims to compare the aging behavior of water-based coatings and solvent-based coatings in sulfuric acid environments and to discuss the related mechanism.

Design/methodology/approach
A sulfuric acid solution with a concentration of 5 Wt.% was selected for immersion test at 23°C. The failure behavior of the coating was studied by combining the transformation rules of the macroscopic morphology and basic properties with the results of electrochemical impedance spectrum analysis.

Findings
The results showed that the surface smoothness of the water-based coating was lower than that of the solvent-based coating. The glossiness, thickness and hardness of the water-based coating exhibited more significant changes. The electrochemical test also indicated that the water-based coating was infiltrated by a large number of corrosive media, which may have induced corrosion under the coating. In contrast, the solvent-based coating showed good shielding properties, but the adhesion was seriously affected by the corrosive medium.

Originality/value
This work clarified the difference of failure behavior and mechanism between water-based coatings and solvent-based coatings in acidic environment and provided a theoretical basis for the selection and mechanism research of anticorrosive coatings.
Benefits and challenges with blockchain technology in global food supply chains: views from the practice
Authors: Beveridge Ivana , Angelis Jannis , Mihajlov Martin 
Published: May 2024

PurposeAlthough technologies such as blockchain (BCT) hold great potential to improve global food supply chains (GFSCs), our understanding of BCT use in GFSCs remains limited. The purpose of this study is to broaden BCT discussions by exploring its benefits and challenges across the entire GFSC.Design/methodology/approachQualitative interviews with 23 industry experts were used to identify and comprehend the nuanced issues with BCT application in GFSCs.FindingsThe study identifies 21 perceived benefits and challenges with BCT use in GFSCs, including the benefit of broader data incentives beyond BCT use and the challenge of reluctance to assume dominant roles among the GFSC actors.Originality/valueWhile prior studies mostly focused on BCT use for traceability and food safety in the GFSC midstream, this study extends the scope to include upstream and midstream actors. It highlights socio-economic benefits for traditionally disadvantaged farmers in the upstream and normative challenges to its adoption in the GFSC midstream and downstream. It also identifies three paradoxes emerging with BCT use in the GFSCs including the paradoxes of food technology, transparency and de-centralization.
Networks perceptions and job satisfaction: the mediating role of perceived organizational support for women’s work contribution
Authors: Pinnington Ashly H. , Aldabbas Hazem , Mirshahi Fatemeh , Brown Mary L. 
Published: May 2024

PurposeThis study investigates the relationship between women’s networks perceptions and job satisfaction. It also examines the mediating effects of perceived organizational support (POS) for women’s work contributions on the relationship between networks perceptions and job satisfaction.Design/methodology/approachThe participants are female employees working in Scotland (n = 247). The data were collected using a survey questionnaire. PROCESS macro (model 4, Hayes, 2018) was used to test the proposed model.FindingsThe results revealed that (controlling for work time, age and sector) there is a significant relationship between women’s networks perceptions and job satisfaction. In addition, POS for women’s work contribution mediates the relationship between networks perceptions and job satisfaction. These findings show the significant effects of networks perceptions on employees’ job, satisfaction directly and through POS for women’s work contributions. Therefore, understanding the networks perceptions of employees and organizational factors will assist in improving job satisfaction.Originality/valueThis study is unique for examining the role of POS for women’s work contribution in the relationship between employees’ networks perceptions and job satisfaction. It addresses gender inequality in the workplace in terms of women’s career advancement and job satisfaction. In addition, this research offers insight into the development of a seven-item measurement scale related to networks perceptions.
Investigation of lightweight gypsum based on montmorillonite nanoclay with enhanced insulation properties
Authors: Anjomshoa Erfan 
Published: May 2024

PurposeNowadays, thermal comfort plays a prominent role in contemporary construction practices. Appropriate thermal insulation not only offers energy efficiency benefits in buildings but also enhances occupant well-being, comfort, and productivity. Therefore, a comprehensive understanding of the thermal properties of building materials is essential. This research aims to prepare and investigate a lightweight gypsum-based composite incorporating nano montmorillonite with advanced thermal insulation properties, considering both quality and cost-effectiveness while ensuring environmental compatibility.Design/methodology/approachThis study adopts a laboratory experimental approach. A gypsum sample (without additives) and seven samples of gypsum combined with varying percentages of sodium and calcium montmorillonite nanoclays undergo extensive testing and analysis. Subsequently, the properties of these samples are compared.FindingsThe results indicate that adding montmorillonite nanoclays to gypsum composites reduces the density of the tested samples and increases their porosity. Moreover, the thermal conductivity coefficient decreases in these samples, significantly improving the thermal insulation properties of the lightweight gypsum plaster. This improvement is more pronounced in samples containing sodium montmorillonite nanoclay compared to calcium-based samples. Additionally, the investigations reveal that compressive strength decreases with the addition of montmorillonite to the samples.Originality/valueIn this research, laboratory experiments were conducted to investigate the physical and mechanical properties of gypsum plaster with varying percentages of sodium and calcium montmorillonite nanoclays. The studied properties include density, porosity, thermal conductivity coefficient, and compressive strength. Additionally, stress-strain diagrams, elastic modulus, and initial and secondary critical stresses were analyzed for each specimen.
Learner attitudes, satisfaction and success in online learning environments: a mediation-moderation model for higher educational institutions
Authors: Sokro Evans , Obuobisa-Darko Theresa , Okpattah Bernard 
Published: May 2024

PurposeThis study examines learner satisfaction and success as mechanisms through which online learning quality translates into learners’ continuous intentions of use by extending DeLone and McLean’s information system success model. It also examines the moderating effect of perceived supervisory support and learners’ self-regulation on online learning quality in Higher Education Institutions.Design/methodology/approachSurvey data were obtained from 540 students in both private and public higher institutions of learning in Ghana. The Partial Least Squares – Structural Equations Modelling (PLS-SEM) technique was used to test the hypothesised relationships.FindingsThe results revealed that system quality emerged as the single most important variable in the DeLone and McLean model, that influences learner success and satisfaction. Further, learner satisfaction has a significant positive effect on learner attitudes, whilst self-regulation was found to moderate the relationship between online learning quality and learner success as well as learner satisfaction.Originality/valueThe study appears to be among the first to explore the inter-relationship among online learning environment quality and learner attitudes and moderating factors perceived supervisory support and self-regulation. The study highlights insightful practical implications for students, faculty and administrators of higher institutions.