bluuebunny/crossref_metadata_2025 huggingface dataset:
A fast and sensitive size-exclusion chromatography method for plasma extracellular vesicle proteomic analysis
Authors: Ludovico Ivo Díaz , Powell Samantha M. , Many Gina , Bramer Lisa , Sarkar Soumyadeep , Stratton Kelly , Liu Tao , Shi Tujin , Qian Wei-Jun , Burnum-Johnson Kristin E , Melchior John T. , Nakayasu Ernesto S.
Published: January 2024

Extracellular vesicles (EVs) carry diverse biomolecules derived from their parental cells, making their components excellent biomarker candidates. However, purifying EVs is a major hurdle in biomarker discovery since current methods require large amounts of samples, are time-consuming and typically have poor reproducibility. Here we describe a simple, fast, and sensitive EV fractionation method using size exclusion chromatography (SEC) on a fast protein liquid chromatography (FPLC) system. Our method uses a Superose 6 Increase 5/150, which has a bed volume of 2.9 mL. The FPLC system and small column size enable reproducible separation of only 50 µL of human plasma in 15 minutes. To demonstrate the utility of our method, we used longitudinal samples from a group of individuals that underwent intense exercise. A total of 838 proteins were identified, of which, 261 were previously characterized as EV proteins, including classical markers, such as cluster of differentiation (CD)9 and CD81. Quantitative analysis showed low technical variability with correlation coefficients greater than 0.9 between replicates. The analysis captured differences in relevant EV-proteins involved in response to physical activity. Our method enables fast and sensitive fractionation of plasma EVs with low variability, which will facilitate biomarker studies in large clinical cohorts.
The N-terminus ofPlasmodium falciparumCircumsporozoite Protein Contains Three Non-Overlapping Murine B-cell Epitope Regions
Authors: Beutler Nathan , Garcia Elijah , Lai Yen-Chung , Ndihokubwayo Justin , Gambuzza Kiara , Zhao Jerry , Burton Dennis R. , Rogers Thomas F.
Published: January 2024

The generation of an anti-malarial vaccine that produces broad, potent, and durable responses is highly desirable to control the burden ofPlasmodium falciparumdisease. Current vaccines have offered modest efficacy ranging from 50%-70%, likely associated with antibody responses that are relatively short lived and strain specific. Currently approved malaria vaccines, RTS,S and R21, target the repeat region and C-terminal region ofPlasmodium falciparumCSP, leaving the N-terminal region of CSP neglected as a target for protective immunogen design. Here, we isolate and express a panel of memory B-cell derived N-terminal CSP-specific monoclonal antibodies (mAbs) from mice immunized with an N-terminal CSP specific immunogen. The characterization of N-terminal specific mAbs including peptide walking and affinity experiments indicate that these antibodies target three distinct sites within the N-terminus of CSP. Site ntCSP-A contains the Region I (RI) cleavage site, which has been previously defined, whereas the remaining two sites are in previously undescribed locations upstream of RI, termed ntCSP-B and ntCSP-C.
nf-core/airrflow: an adaptive immune receptor repertoire analysis workflow employing the Immcantation framework
Authors: Gabernet Gisela , Marquez Susanna , Bjornson Robert , Peltzer Alexander , Meng Hailong , Aron Edel , Lee Noah Y. , Jensen Cole , Ladd David , Hanssen Friederike , Heumos Simon ,   nf-core community, Yaari Gur , Kowarik Markus C. , Nahnsen Sven , Kleinstein Steven H.
Published: January 2024

Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a valuable experimental tool to study the immune state in health and following immune challenges such as infectious diseases, (auto)immune diseases, and cancer. Several tools have been developed to reconstruct B cell and T cell receptor sequences from AIRR-seq data and infer B and T cell clonal relationships. However, currently available tools offer limited parallelization across samples, scalability or portability to high-performance computing infrastructures. To address this need, we developed nf-core/airrflow, an end-to-end bulk and single-cell AIRR-seq processing workflow which integrates the Immcantation Framework following BCR and TCR sequencing data analysis best practices. The Immcantation Framework is a comprehensive toolset, which allows the processing of bulk and single-cell AIRR-seq data from raw read processing to clonal inference. nf-core/airrflow is written in Nextflow and is part of the nf-core project, which collects community contributed and curated Nextflow workflows for a wide variety of analysis tasks. We assessed the performance of nf-core/airrflow on simulated sequencing data with sequencing errors and show example results with real datasets. To demonstrate the applicability of nf-core/airrflow to the high-throughput processing of large AIRR-seq datasets, we validated and extended previously reported findings of convergent antibody responses to SARS-CoV-2 by analyzing 97 COVID-19 infected individuals and 99 healthy controls, including a mixture of bulk and single-cell sequencing datasets. Using this dataset, we extended the convergence findings to 20 additional subjects, highlighting the applicability of nf-core/airrflow to validate findings in small in-house cohorts with reanalysis of large publicly available AIRR datasets.

Availability and implementation

nf-core/airrflow is available free of charge, under the MIT license on GitHub (https://github.com/nf-core/airrflow). Detailed documentation and example results are available on the nf-core website at (https://nf-co.re/airrflow).

Visual abstract
Acceleration of HDL-mediated cellular cholesterol efflux alleviates periodontitis
Authors: Tran Thanh-Tam , Lee Gyuseok , Huh Yun Hyun , Chung Ki-Ho , Lee Sun Young , Park Ka Hyon , Kook Min-Suk , Ryu Jaeyoung , Kim Ok-Su , Lim Hyun-Pil , Koh Jeong-Tae , Ryu Je-Hwang
Published: January 2024

Periodontitis (PD) is a common inflammatory disease known to be closely associated with metabolic disorders, particularly hyperlipidemia. However, direct evidence is lacking, and the molecular mechanism is yet to be examined. In the current study, we demonstrated that hypercholesterolemia is a causative factor in the development of PD. Logistic regression analysis revealed a strong positive correlation between PD and dyslipidemia. Data fromin vivo(PD mouse model subjected to a high cholesterol diet) andin vitro(cholesterol treatment of periodontal cells) experiments showed that excess cholesterol influx into periodontal cells potentially contributes to periodontal inflammation and subsequently, alveolar bone erosion. Additionally, we compared the protective efficacies of cholesterol-lowering drugs with their different modes of action against PD pathogenesis in mice. Among the cholesterol-lowering drugs we tested, fenofibrate exerted the most protective effect against PD pathogenesis, due to an increased level of high-density lipoprotein cholesterol, a lipoprotein involved in cholesterol efflux from cells and reverse cholesterol transport. Indeed, cholesterol efflux was suppressed during PD progression by downregulation of the apoA-I binding protein (APOA1BP) expression in inflamed gingival fibroblasts and periodontal ligament cells. We also demonstrated that the overexpression of APOA1BP efficiently regulated periodontal inflammation and the subsequent alveolar bone loss by inducing cholesterol efflux. Our collective findings highlight the potential utility of currently available cholesterol-lowering medications for the mitigation of PD pathogenesis. By targeting the acceleration of high-density lipoprotein (HDL)-mediated cellular cholesterol efflux, a new therapeutic approach for PD may become possible.
Regulatory and evolutionary impact of DNA methylation in two songbird species and their naturally occurring F1hybrids
Authors: Boman Jesper , Qvarnström Anna , Mugal Carina F.
Published: January 2024

Regulation of transcription by DNA methylation in 5’-CpG-3’ context is a widespread mechanism allowing differential expression of genetically identical cells to persist throughout development. Consequently, differences in DNA methylation can reinforce variation in gene expression among cells, tissues, populations and species. Despite a surge in studies on DNA methylation, we know little about the importance of DNA methylation in population differentiation and speciation. Here we investigate the regulatory and evolutionary impact of DNA methylation in five tissues of twoFicedulaflycatcher species and their naturally occurring F1hybrids. We show that the density of CpG in the promoters of genes determines the strength of the association between gene expression and DNA methylation. The impact of DNA methylation on gene expression varies among tissues with brain showing unique patterns. Differentially expressed genes between parental species are predicted by genetic– and methylation differentiation in CpG-rich promoters. However, both these factors fail to predict hybrid misexpression suggesting that promoter mismethylation is not a main determinant of hybrid misexpression inFicedulaflycatchers. Using allele-specific methylation estimates in hybrids we also determine the genome-wide contribution ofcis-andtranseffects in DNA methylation differentiation. These distinct mechanisms are roughly balanced in all tissues except brain, wheretransdifferences predominate. Overall, this study provides insight on the regulatory and evolutionary impact of DNA methylation in songbirds.
Psilocybin biphasically modulates cortical and behavioral activity in mice
Authors: Brockett Adam T. , Francis Nikolas A.
Published: January 2024

Psilocybin is a serotonergic psychedelic believed to have therapeutic potential for neuropsychiatric conditions. Despite well-documented prevalence of perceptual alterations, hallucinations, and synesthesia associated with psychedelic experiences, little is known about how psilocybin affects sensory cortex or alters the activity of neurons in awake animals. To investigate, we conducted 2-photon imaging experiments in auditory cortex of awake mice and video analysis of mouse behavior, both at baseline and during psilocybin treatment. We found biphasic effects of psilocybin on behavioral and cortical activity. A 2 mg/kg dose of psilocybin initially increased behavioral activity and neural responses to sound. 30 minutes post-dose, mice became behaviorally hypoactive and cortical responses to sound decreased, while neural response variance and noise correlations increased. In contrast, neuronal selectivity for auditory stimuli remained stable during psilocybin treatment. Our results suggest that psilocybin modulates the role of intrinsic versus stimulus-driven activity in sensory cortex, while preserving fundamental sensory processing.Graphical Abstract.

Summary of psilocybin’s effect on auditory cortical responses to sound in mice.

30 minutes after injecting the inert vehicle saline, typical auditory responses occur within a relatively narrow range of possible amplitudes, i.e., each neuron’s response variance is weakly correlated with a neighboring neuron’s response variance. In contrast, 30 minutes after injecting 2 mg/kg of psilocybin, population response variance becomes more correlated between individual neurons, and the range of response amplitudes increases. These findings suggest that psilocybin modulates the role of intrinsic versus stimulus-driven neural activity in sensory perception, which may serve as a basis for auditory hallucination at the level of neuronal micro-circuits.
Engineering CRBN for rapid identification of next generation binders
Authors: Bailey Henry J. , Eisert Jonathan , Vollrath Joshua , Leibrock Eva-Maria , Kondratov Ivan , Matviyuk Tetiana , Tolmachova Nataliya , Langer Julian D. , Wegener Ansgar A. , Sorrell Fiona J. , Dikic Ivan
Published: January 2024

The majority of clinical degrader candidates utilize an immunomodulatory imide drug (IMiD)-based derivative, that directs their target substrate to the E3 ligase receptor Cereblon (CRBN), however, concomitant neo-substrate degradation by IMiDs often results in severe off-target effects. Further biophysical screening is needed to discover CRBN binders that might overcome these safety concerns, but the previously reported CRBN protein constructs suffer significant limitations that reduce their applicability as tools for biophysical assays making large-scale screening efforts a costly endeavor. This is due to the requirement of CRBN co-expression with DDB1 in insect cells to produce soluble protein that contains all the reported structural features necessary for proper compound interaction. Here, a near full-length human CRBN construct was designed that retains these required features, but for the first time allows the generation of highly homogenous and cost-efficient expression inE.coli, eliminating the need for DDB1 co-expression. We have extensively profiled the new construct against the existing CRBN constructs in binary and ternary degrader complexes, showing it to be the “best of both worlds” in terms of binding characteristics and ease of protein production. We then designed the Enamine CRBN focused IMiD library of 4480-compounds and demonstrated applicability of the new construct to high throughput screening by identifying novel CRBN binders with high potency and ligand efficiency. The new methods described here should serve as valuable tools for the development of the next generation IMiD-based degraders.
Structural features of heteromeric channels composed of CALHM2 and CALHM4 paralogs
Authors: Drożdżyk Katarzyna , Peter Martina , Dutzler Raimund
Published: January 2024

The CALHM proteins constitute a family of large pore channels that contains six closely related paralogs in human. Two family members, CALHM1 and 3, have been associated with the release of ATP during taste sensation. Both proteins form heteromeric channels that activate at positive potential and decreased extracellular Ca2+concentration. Although the structures of several family members displayed large oligomeric organizations of different size, their function has in most cases remained elusive. Our previous study has identified the paralogs CALHM2, 4 and 6 to be highly expressed in the placenta and defined their structural properties as membrane proteins exhibiting features of large pore channels with unknown activation properties (Drozdzyk et al., 2020). Here we investigated whether these placental paralogs would form heteromers and characterized heteromeric complexes consisting of CALHM2 and CALHM4 subunits using specific binders as fiducial markers. Both proteins assemble with different stoichiometries with the largest population containing CALHM2 as predominant component. In these oligomers, the subunits segregate and reside in their preferred conformation found in homomeric channels. Our study has thus revealed the properties that govern the formation of CALHM heteromers in a process of potential relevance in a cellular context.
Alteration of long and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesis
Authors: Nishi Katsuyuki , Sakamaki Taro , Nagasaka Akiomi , Kao Kevin S. , Sadaoka Kay , Asano Masahide , Yamamoto Nobuyuki , Takaori-Kondo Akifumi , Miyanishi Masanori
Published: January 2024

Myeloid-biased hematopoiesis is a well-known age-related alteration. Several possibilities, including myeloid-biased hematopoietic stem cell (HSC) clones, may explain this. However, the precise mechanisms remain controversial.

Utilizing the Hoxb5 reporter system to prospectively isolate long-term HSCs (LT-HSCs) and short-term HSCs (ST-HSCs), we found that young and aged LT-HSCs co-transplanted into the same recipients demonstrated nearly equivalent myeloid lineage output, contrary to the theory of myeloid-biased HSC clones. Transcriptomics indicated no significant myeloid gene enrichment in aged LT-HSCs compared to their young counterparts. Instead, transplanting reconstituted young HSCs with the ratio of LT/ST-HSCs seen in aged mice can significantly skew the lineage output to myeloid cells. In addition, while the niche environment in the bone marrow minimally affects myeloid-biased hematopoiesis, aged thymi and spleens substantially hinder lymphoid hematopoiesis, resulting in further myeloid-domination. Thus, we demonstrate that myeloid-biased hematopoiesis in aged organisms originates due to alteration of the ratio between LT-HSCs and ST-HSCs rather than in heterogeneous HSC clones with various cell fates.
Binding profiles for 954 Drosophila andC. eleganstranscription factors reveal tissue specific regulatory relationships
Authors: Kudron Michelle , Gevirtzman Louis , Victorsen Alec , Lear Bridget C. , Gao Jiahao , Xu Jinrui , Samanta Swapna , Frink Emily , Tran-Pearson Adri , Huynh Chau , Vafeados Dionne , Hammonds Ann , Fisher William , Wall Martha , Wesseling Greg , Hernandez Vanessa , Lin Zhichun , Kasparian Mary , White Kevin , Allada Ravi , Gerstein Mark , Hillier LaDeana , Celniker Susan E. , Reinke Valerie , Waterston Robert H.
Published: January 2024

A catalog of transcription factor (TF) binding sites in the genome is critical for deciphering regulatory relationships. Here we present the culmination of the modERN (model organism Encyclopedia of Regulatory Networks) consortium that systematically assayed TF binding events in vivo in two major model organisms,Drosophila melanogaster(fly) andCaenorhabditis elegans(worm). We describe key features of these datasets, comprising 604 TFs identifying 3.6M sites in the fly and 350 TFs identifying 0.9 M sites in the worm. Applying a machine learning model to these data identifies sets of TFs with a prominent role in promoting target gene expression in specific cell types. TF binding data are available through the ENCODE Data Coordinating Center and athttps://epic.gs.washington.edu/modERNresource, which provides access to processed and summary data, as well as widgets to probe cell type-specific TF-target relationships. These data are a rich resource that should fuel investigations into TF function during development.
Layered entrenchment maintains essentiality in protein-protein interactions
Authors: Schulz Luca , Zarzycki Jan , Steinchen Wieland , Hochberg Georg K. A. , Erb Tobias J.
Published: January 2024

Protein complexes composed of strictly essential subunits are abundant in nature and arise through the gradual complexification of ancestral precursor proteins followed by their co-evolution with the newly recruited components. Essentiality arises during co-evolution by the accumulation of changes that are tolerated in the complex state but would be deleterious for the standalone complex components. While this theoretical framework to explain how essentiality arises has been proposed long ago, it is unclear which factors cause essentiality to persist over evolutionary timescales. In this work we show that the central enzyme of photosynthesis, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), rapidly started to depend on a newly recruited interaction partner through multiple, genetically distinct mechanisms that affect stability, solubility, and catalysis. We further demonstrate that layering multiple mechanisms of essentiality can lead to the persistence of essentiality, even if any given mechanism reverts through chance or selection. More broadly, our work highlights that new interaction partners can drastically re-shape which substitutions are tolerated in the proteins they are recruited into. This can lead to the rapid evolution of multi-layered essentiality through the exploration of areas of sequence space that are only accessible in the complex state.
PINK1 knockout rats show premotor cognitive deficits measured through a complex maze
Authors: Soto Isabel , Nejtek Vicki A. , Siderovski David P. , Salvatore Michael F.
Published: January 2024

Cognitive decline in Parkinson’s disease (PD) emerges up to 10 years before clinical recognition. Neurobiological mechanisms underlying premotor cognitive impairment in PD can potentially be examined in the PINK1-/-rat, which exhibits a protracted motor onset. To enhance translation to human PD cognitive assessments, we tested a modified multiple T-maze, which measures cognitive flexibility similarly to the Trail-Making Test in humans. Like human PD outcomes, PINK1-/-rats made more errors and took longer to complete the maze than wild types. Thus, we have identified a potential tool for assessing cross-species translation of cognitive functioning in an established PD animal model.
Dermal wound healing contribution of aqueous extracts ofAcalypha indica, Calotropis gigantea, Bacopa monnieriand their combination
Authors: Tanimu Habibu , Zirmire K Ravindra , Jamora Colin , Karthik Parimala , Bindhu O.S
Published: January 2024

Wound healing is a complex process that requires a well-orchestrated integration of an array of molecular events such as cell migration and proliferation, deposition and remodeling of extracellular matrix components for restoring the structural and functional integrity of the tissue injured. Ayurveda suggests wound healing herbs can achieve enhanced therapeutic effect with reduced toxicity when they are optimally combined in a specific ratio as polyherbal formulation (PHF). The present study was aimed to evaluate the combinatorial wound healing efficacy (in vivowound closure and histological changes) of aqueous extracts of three medicinal plants (Bacopa monnieri,Acalypha indicaandCalotropis gigantea). This study also explored how the combination influenced the overall quality of healed wound. Individual wound closure kinetic performance of aqueous plant extracts in C57B/6J mice was assessed using safe concentrations obtained from human adult dermal fibroblast viability assay. The aqueous plant extract combination optimized using response surface methodology was tested forin vivowound closure effectiveness. Quality of healed wound was assessed via Hematoxylin & Eosin and immunohistochemical staining of markers (K1, K5, Loricrin, Ki67, CD31 and collagen1). The combination treatment(B.monnieri-15μg/ml,A.indica-11.59μg/ml,C.gigantea-1μg/ml) contributed to faster wound closure (11 days), improved collagen type I remodeling and angiogenesis, complete re-epithelialization, similar epidermal differentiation pattern as that of individual and control treatments. Ki67 staining revealed no significant increase in cell proliferation in combination compared to individual and control. Findings from the study validates the polyherbal combination’s impressive capability to promote wound healing.
FAP20 is required for flagellum assembly inTrypanosoma brucei
Authors: Shimogawa Michelle M. , Jonnalagadda Keya , Hill Kent L.
Published: January 2024

Trypanosoma bruceiis a human and animal pathogen that depends on flagellar motility for transmission and infection. The trypanosome flagellum is built around a canonical “9+2” axoneme, containing nine doublet microtubules (DMTs) surrounding two singlet microtubules. Each DMT contains a 13-protofilament A-tubule and a 10-protofilament B-tubule, connected to the A-tubule by a conserved, non-tubulin inner junction (IJ) filament made up of alternating PACRG and FAP20 subunits. Here we investigate FAP20 in procyclic formT. brucei. A FAP20-NeonGreen fusion protein localized to the axoneme as expected. Surprisingly, FAP20 knockdown led to a catastrophic failure in flagellum assembly and concomitant lethal cell division defect. This differs from other organisms, where FAP20 is required for normal flagellum motility, but generally dispensable for flagellum assembly and viability. Transmission electron microscopy demonstrates failed flagellum assembly in FAP20 mutants is associated with a range of DMT defects and defective assembly of the paraflagellar rod, a lineage-specific flagellum filament that attaches to DMT 4-7 in trypanosomes. Our studies reveal a lineage-specific requirement for FAP20 in trypanosomes, offering insight into adaptations for flagellum stability and motility in these parasites and highlighting pathogen versus host differences that might be considered for therapeutic intervention in trypanosome diseases.

SIGNIFICANCE STATEMENT

Diverse eukaryotic organisms rely on a generally conserved axoneme architecture and dynein-dependent beating mechanism to drive motility, but mechanisms conferring lineage-specific motility needs are largely unknown.

FAP20 is a conserved flagellar protein that impacts flagellum motility in multiple organisms.

The current work demonstrates FAP20 is particularly important in the pathogen,T. brucei, providing insight into pathogen adaptations for moving through host environments and illuminating targets to consider for therapeutic intervention in trypanosome diseases.
Sterol O-acyltransferase (SOAT/ACAT) activity is required to form cholesterol crystals in hepatocyte lipid droplets
Authors: Bairos Jordan A , Njoku Uche , Zafar Maria , Akl May G , Li Lei , Parlakgul Gunes , Arruda Ana Paula , Widenmaier Scott B
Published: January 2024

Objective

Excess unesterified (free) cholesterol can induce formation of cholesterol crystals in hepatocyte lipid droplets. Presence of such crystal distinguishes metabolic dysfunction associated steatohepatitis (MASH) from simple steatosis and may underlie its pathogenesis by causing cell damage that triggers liver inflammation. The mechanism linking cholesterol excess to its crystallization in lipid droplets is unclear. As cholesteryl esters localize to and accumulate in lipid droplets much more readily than free cholesterol, we investigated whether cholesterol esterification by sterol O-acyltransferase (SOAT), also known as acyl co-A cholesterol acyltransferase (ACAT) is required for hepatocyte lipid droplet crystal formation.

Method

Cholesterol crystals were measured in cholesterol loaded Hep3B hepatocytes, RAW264.7 macrophages and mouse liver using polarizing light microscopy. We examined the effect of blocking SOAT activity on crystal formation and compared these results to cholesterol metabolism and the progression to intracellular crystal deposits.

Results

Cholesterol loading of Hep3B cells caused robust levels of lipid droplet localized crystal formation in a dose- and time-dependent manner. Co-treatment with SOAT inhibitors and genetic ablation ofSOAT1blocked crystal formation. SOAT inhibitor also blocked crystal formation in low density lipoprotein (LDL) treated Hep3B cells, acetylated LDL treated RAW 264.7 macrophages, and in the liver of mice genetically predisposed to hepatic cholesterol overload and in mice fed a cholesterol enriched, MASH-promoting diet for 24 weeks.

Conclusion

SOAT1-mediated esterification may underlie cholesterol crystals associated with MASH by concentrating it in lipid droplets. These findings imply that inhibiting hepatocyte SOAT1 may alleviate cholesterol associated MASH. Moreover, that a lipid droplet localized cholesteryl ester hydrolase may be required for cholesterol crystal formation or, instead, that the crystals are composed of cholesteryl ester.

Funding Sources

Grants supporting this research were awarded to SBW from the Natural Sciences and Engineering Research Council of Canada (NSERC). SBW was supported by a National New Investigator Award and McDonald Scholarship from the Heart and Stroke Foundation of Canada. UN and MA were supported by a James Regan Cardiology Research scholarship from University of Saskatchewan’s College of Medicine.
AXONAL distribution of mitochondria maintains neuronal autophagy during aging via eIF2β
Authors: Shinno Kanako , Miura Yuri , Iijima Koichi M. , Suzuki Emiko , Ando Kanae
Published: January 2024

Neuronal aging and neurodegenerative diseases are accompanied by proteostasis collapse, while cellular factors that trigger it are not identified. Impaired mitochondrial transport in the axon is another feature of aging and neurodegenerative diseases. UsingDrosophila, we found that genetic depletion of axonal mitochondria causes dysregulation of protein degradation. Axons with mitochondrial depletion showed abnormal protein accumulation and autophagic defects. Lowering neuronal ATP levels by blocking glycolysis did not reduce autophagy, suggesting that autophagic defects are associated with mitochondrial distribution. We found that eIF2β was increased by the depletion of axonal mitochondria via proteome analysis. Phosphorylation of eIF2α, another subunit of eIF2, was lowered, and global translation was suppressed. Neuronal overexpression ofeIF2βphenocopied the autophagic defects and neuronal dysfunctions, and loweringeIF2βexpression rescued those perturbations caused by depletion of axonal mitochondria. These results indicate the mitochondria-eIF2β axis maintains proteostasis in the axon, of which disruption may underly the onset and progression of age-related neurodegenerative diseases.

Highlights

Loss of axonal mitochondria impairs autophagy and accumulates proteins in the axon

Loss of axonal mitochondria increases eIF2β and decreases p-eIF2α

Neuronal upregulation of eIF2β induces autophagic defects and locomotor dysfunction

Lowering eIF2β rescues autophagic defects caused by loss of axonal mitochondria
Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development
Authors: Caccavano Adam P. , Vlachos Anna , McLean Nadiya , Kimmel Sarah , Kim June Hoan , Vargish Geoffrey , Mahadevan Vivek , Hewitt Lauren , Rossi Anthony M. , Spineux Ilona , Wu Sherry Jingjing , Furlanis Elisabetta , Dai Min , Garcia Brenda Leyva , Wang Yating , Chittajallu Ramesh , London Edra , Yuan Xiaoqing , Hunt Steven , Abebe Daniel , Eldridge Mark A. G. , Cummins Alex C. , Hines Brendan E. , Plotnikova Anya , Mohanty Arya , Averbeck Bruno B. , Zaghloul Kareem , Dimidschstein Jordane , Fishell Gord , Pelkey Kenneth A. , McBain Chris J.
Published: January 2024

Within the adult rodent hippocampus, opioids suppress inhibitory parvalbumin-expressing interneurons (PV-INs), thus disinhibiting local micro-circuits. However, it is unknown if this disinhibitory motif is conserved in other cortical regions, species, or across development. We observed that PV-IN mediated inhibition is robustly suppressed by opioids in hippocampus proper but not primary neocortex in mice and nonhuman primates, with spontaneous inhibitory tone in resected human tissue also following a consistent dichotomy. This hippocampal disinhibitory motif was established in early development when PV-INs and opioids were found to regulate early population activity. Acute opioid-mediated modulation was partially occluded with morphine pretreatment, with implications for the effects of opioids on hippocampal network activity important for learning and memory. Together, these findings demonstrate that PV-INs exhibit a divergence in opioid sensitivity across brain regions that is remarkably conserved across evolution and highlights the underappreciated role of opioids acting through immature PV-INs in shaping hippocampal development.
Effects of heater positions on magneto-hydrodynamic convection of CuO-water nanofluid flow in a grooved channel
Authors: Rahaman Md Motiur , Biswas Nirmalendu , Santra Apurba Kumar , Manna Nirmal K.
Published: January 2024

Purpose

This study aims to delve into the coupled mixed convective heat transport process within a grooved channel cavity using CuO-water nanofluid and an inclined magnetic field. The cavity undergoes isothermal heating from the bottom, with variations in the positions of heated walls across the grooved channel. The aim is to assess the impact of heater positions on thermal performance and identify the most effective configuration.

Design/methodology/approach

Numerical solutions to the evolved transport equations are obtained using a finite volume method-based indigenous solver. The dimensionless parameters of Reynolds number (1 ≤ Re ≤ 500), Richardson number (0.1 ≤ Ri ≤ 100), Hartmann number (0 ≤ Ha ≤ 70) and magnetic field inclination angle (0° ≤ γ ≤ 180°) are considered. The solved variables generate both local and global variables after discretization using the semi-implicit method for pressure linked equations algorithm on nonuniform grids.

Findings

The study reveals that optimal heat transfer occurs when the heater is positioned at the right corner of the grooved cavity. Heat transfer augmentation ranges from 0.5% to 168.53% for Re = 50 to 300 compared to the bottom-heated case. The magnetic field’s orientation significantly influences the average heat transfer, initially rising and then declining with increasing inclination angle. Overall, this analysis underscores the effectiveness of heater positions in achieving superior thermal performance in a grooved channel cavity.

Research limitations/implications

This concept can be extended to explore enhanced thermal performance under various thermal boundary conditions, considering wall curvature effects, different geometry orientations and the presence of porous structures, either numerically or experimentally.

Practical implications

The findings are applicable across diverse fields, including biomedical systems, heat exchanging devices, electronic cooling systems, food processing, drying processes, crystallization, mixing processes and beyond.

Originality/value

This work provides a novel exploration of CuO-water nanofluid flow in mixed convection within a grooved channel cavity under the influence of an inclined magnetic field. The influence of different heater positions on thermomagnetic convection in such a cavity has not been extensively investigated before, contributing to the originality and value of this research.
Analysing the mediating role of organisational citizenship behaviour between transformational leadership and education 4.0 using PLS-SEM approach
Authors: Sharma Rajesh Kumar , Kaur Sukhpreet
Published: January 2024

Purpose

The purpose of this paper is to analyse the mediating role of organisational citizenship behaviour between transformational leadership and successful implementation of education 4.0 in higher educational institutes using the PLS-SEM approach.

Design/methodology/approach

The study uses cross-sectional and quantitative approach to decode the relationship amongst the variables. Purposive non-probability sampling technique was used to select the sample size for the study.

Findings

The research findings reveal that transformational leadership has a significant and positive effect on education 4.0. Further, it also indicates that the organisational citizenship behaviour in the study served as a mediating variable between transformational leadership and education 4.0, explaining 40% of the effect of transformational leadership on education 4.0. This highlights the importance of transformational leaders in creating a conducive environment that encourages employees to exhibit organisational citizenship behaviour, thereby facilitating the successful adoption and integration of education 4.0.

Originality/value

The authors recognise a research gap in the existing literature that focusses on the direct effects of transformational leadership on education 4.0 in higher educational institutes of management. Also, there is a lack of inclusive studies that explore the mediating mechanisms through which transformational leadership affects education 4.0, predominantly the role of organisational citizenship behaviour. Thus, this study is first in itself to explore the inter relationship between transformational leadership, organisational citizenship behaviour and education 4.0.
Prediction of tourists' intention toward domestic vs international destinations in post-COVID-19 recovery: the role of COVID-19, future anxiety and solidarity
Authors: Küçükergin Kemal Gürkan , Özekici Yakup Kemal , Güzel Şahin Gonca
Published: January 2024

Purpose

This paper aims to investigate, upon taking into consideration both symmetric and asymmetric effects, how the economic and psychological impact of the coronavirus disease 2019 (COVID-19) pandemic, solidarity and future anxiety affect travel intention and the willingness to support a destination (WSD). Furthermore, the study sheds light on whether these relationships vary between domestic and international destinations.

Design/methodology/approach

The data are collected from 379 potential tourists. To detect and analyze the symmetrical and asymmetric effects, the covariance-based structural equation modeling (CB-SEM) and the fuzzy-set qualitative comparative analysis (fsQCA) are employed, respectively.

Findings

It is observed that, whereas only the effects of solidarity on travel intention and WSD differ in the CB-SEM, the fsQCA results include different recipes for the two groups.

Originality/value

There has not been much research done yet on the influence of future anxiety on tourists' decisions. Furthermore, it has not been thoroughly investigated whether solidarity has a different function for destinations within and outside of the country. In this respect, the study of both symmetric and asymmetric effects represents an important contribution to the literature.
Technology-enhanced language and culture teaching in Chile: the perceptions and practices of in-service EFL teachers
Authors: Gonzalez-Vidal Tiare , Moore Paul
Published: January 2024

Purpose

The professional experiences of teachers of languages and cultures, along with the learning experiences of their students, are embedded in educational contexts, which themselves are informed, and constrained, by national language policies. This study aims to explore 51 English-as-a-foreign-language (EFL) secondary teachers’ perceptions of Web-based technology use to enhance students’ cultural awareness in Chile. Specifically, the study investigated teachers’ use of Web-based resources for cultural awareness, culture content and technology-based tasks, as well as perceived challenges in implementing technology-enhanced language and culture learning.

Design/methodology/approach

The study adopted a mixed-method research design combining online questionnaires and interviews as data collection tools. Results were analyzed through the use of descriptive statistics and content analysis.

Findings

The teachers in this study emphasized reflection in their classrooms but did not take a critical approach. Their approach to culture was limited to a “country-specific” view, and technology-enhanced activities accentuated differences rather than promoting meaningful intercultural exchange. Challenges to the successful implementation of technology-enhanced language and culture learning included a somewhat out-of-date theoretical approach to intercultural learning in the national curriculum, a nationwide approach to professional development that lacks a focus on critical reflection and inadequate support for effective use of technologies in schools.

Practical implications

The study highlights the importance of periodically revising a country’s EFL language policies, communication methods, support mechanisms and implementation factors to ensure classroom integration of language, culture and technology education.

Originality/value

This paper explores the tension between macro-level national policy and teachers’ perspectives on their classroom practice, including the contextualized limitations of implementing national policy at the micro level.
Prioritizing user preferences for quasi – Public space by using analytic hierarchy process (AHP): bursa Podyum park, Turkey case
Authors: Ersoz Nazli Deniz , Demir Sara , Dilman Gokkaya Merve , Aksoy Onur
Published: January 2024

Purpose

This study aims to fill the lack of quantitative studies of user preferences in quasi-public spaces to observe the use of quasi-public spaces by questioning the contemporary needs of urban communities and to develop design strategies accordingly.

Design/methodology/approach

Within the scope of this study, public space design elements affecting users' preferences in the quasi-public spaces of the Podium Park shopping center in Bursa, Turkey were evaluated. By considering the spatial characteristics of the study area, 4 main and 15 subcriteria were determined and utilized by analytic hierarchy process (AHP). These criteria were evaluated by experts and locals with a participatory approach.

Findings

According to the obtained results, “events” (S2), “sun/shade” (C2), “safety” (P3) and “planting” (U4) subcriteria were determined as the vital elements for quasi-public spaces.

Originality/value

Although the concept of quasi-public space has been discussed for nearly 30 years, it has been observed that there are no quantitative studies to determine the criteria of user preferences in these open spaces in the literature. This study is the first quantitative research for user preferences in quasi-public spaces and there is no previous study on this subject and study area in Turkey.
Behavioral biases of cryptocurrency investors: a prospect theory model to explain cryptocurrency returns
Authors: Yadav Manisha
Published: January 2024

Purpose

The study aims to test prospect theory (PT) predictions in the cryptocurrency (CC) market. It proposes a new asset pricing model that explores the potential of prospect theory value (PTV) as a significant predictor of CC returns.

Design/methodology/approach

The study comprehensively analyses a large sample set of 1,629 CCs, representing more than 95% of the CC market. The study uses a portfolio analysis approach, employing univariate and bivariate sorting techniques with equal-weighted and value-weighted portfolios. The study also employs ordinary least squares (OLS) regression, panel data methods and quantile regression (QR) to estimate the models.

Findings

This study demonstrates an average inverse relationship between PTV and CC returns. However, this relationship exhibits asymmetry across different quantiles, indicating that investor reactions vary based on market conditions. Moreover, PTV provides more robust predictions for smaller CCs characterized by high volatility and illiquidity. Notably, the findings highlight the dominant role of the probability weighting (PW) component in PT for predicting CC behaviors, suggesting a preference for lottery-like characteristics among CC investors.

Originality/value

The study is one of the early studies on CC price dynamics from the PT perspective. The study is the first to apply a QR approach to analyze the cross-section of CCs using a PT-based asset pricing model. The results shed light on CC investors' decision-making processes and risk perception, offering valuable insights to regulators, policymakers and market participants. From a practical perspective, a trading strategy centered around the PTV effect can be implemented.
Novel role of host protein SLC25A42 in the HIV‐1 reactivation of latent HIV‐1 provirus
Authors: Taga Kei , Takeuchi Hiroaki
Published: January 2024

Despite the effectiveness of combination antiretroviral therapy, human immunodeficiency virus (HIV) infection remains incurable. To seek new strategies to overcome HIV type 1 (HIV‐1) latency, one of the major barriers to HIV elimination, it is crucial to better understand how this state is maintained. Here, by means of an RNA interference screen employing an HIV‐1 latency model using monocytic cell lines, we identified solute carrier family 25 member 42 (SLC25A42) as a potential host factor not previously known to affect HIV‐1 latency. SLC25A42 knockdown resulted in increased HIV‐1 expression, whereas forced expression of exogenous SLC25A42 suppressed it in SLC25A42‐depleted cells. SLC25A42 depletion increased HIV‐1 proviral transcriptional elongation but did not cause HIV‐1 activation in an HIV‐1 Tat‐depleted latency model. This suggests that the role of SLC25A42 in HIV‐1 transcription depends on HIV‐1 Tat. Chromatin immunoprecipitation‐qPCR analysis further revealed that SLC25A42 accumulated on or near the HIV‐1 5ʹ long terminal repeat promoter region of the HIV‐1 provirus, suggesting a possible role in regulating HIV‐1 Tat near this promoter region. These results indicate that SLC25A42 plays a novel role in HIV‐1 latency maintenance in monocytic HIV‐1 reservoirs.
A test of the loose‐equilibrium concept with long‐lived organisms: Evaluating temporal change in freshwater mussel assemblages
Authors: Hopper Garrett W. , Miller Edwin J. , Haag Wendell R. , Vaughn Caryn C. , Hornbach Daniel J. , Jones Jess W. , Atkinson Carla L.
Published: January 2024

The loose‐equilibrium concept (LEC) predicts that ecological assemblages change transiently but return towards an earlier or average structure. The LEC framework can help determine whether assemblages vary within expected ranges or are permanently altered following environmental change.

Long‐lived, slow‐growing animals typically respond slowly to environmental change, and their assemblage dynamics may respond over decades, which transcends most ecological studies. Unionid mussels are valuable for studying dynamics of long‐lived animals because they can live >50 years and occur in dense, species‐rich assemblages (mussel beds). Mussel beds can persist for decades, but disturbance can affect species differently, resulting in variable trajectories according to differences in species composition within and among rivers.

We used long‐term data sets (10–40 years) from seven rivers in the eastern United States to evaluate the magnitude, pace and directionality of mussel assemblage change within the context of the LEC.

Site trajectories varied within and among streams and showed patterns consistent with either the LEC or directional change. In streams that conformed to the LEC, rank abundance of dominant species remained stable over time, but directional change in other streams was driven by changes in the rank abundance and composition of dominant species.

Characteristics of mussel assemblage change varied widely, ranging from those conforming to the LEC to those showing strong directional change. Conservation approaches that attempt to maintain or create a desired assemblage condition should acknowledge this wide range of possible assemblage trajectories and that the environmental factors that influence those changes remain poorly understood.