bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extinction Training Suppresses Activity of Fear Memory Ensembles Across the Hippocampus and Alters Transcriptomes of Fear-Encoding Cells
Authors: Zuniga Alfredo , Han Jiawei , Miller-Crews Isaac , Agee Laura A. , Hofmann Hans A. , Drew Michael R. 
Published: January 2024

ABSTRACTContextual fear conditioning has been shown to activate a set of “fear ensemble” cells in the hippocampal dentate gyrus (DG) whose reactivation is necessary and sufficient for expression of contextual fear. We previously demonstrated that extinction learning suppresses reactivation of these fear ensemble cells and activates a competing set of DG cells – the “extinction ensemble.” Here, we tested whether extinction was sufficient to suppress reactivation in other regions and used single nucleus RNA sequencing (snRNA-seq) of cells in the dorsal dentate gyrus to examine how extinction affects the transcriptomic activity of fear ensemble and fear recall-activated cells. Our results confirm the suppressive effects of extinction in the dorsal and ventral dentate gyrus and demonstrate that this same effect extends to fear ensemble cells located in the dorsal CA1. Interestingly, the extinction-induced suppression of fear ensemble activity was not detected in ventral CA1. Our snRNA-seq analysis demonstrates that extinction training markedly changes transcription patterns in fear ensemble cells and that cells activated during recall of fear and recall of extinction have distinct transcriptomic profiles. Together, our results indicate that extinction training suppresses a broad portion of the fear ensemble in the hippocampus, and this suppression is accompanied by changes in the transcriptomes of fear ensemble cells and the emergence of a transcriptionally unique extinction ensemble.
Functional consequences of reductive protein evolution in a minimal eukaryotic genome
Authors: Jiang Jason , Qu Rui , Grigorescu Maria , Zhao Winnie , Reinke Aaron W. 
Published: January 2024

AbstractMicrosporidia are parasites with the smallest known eukaryotic genomes. The extent of protein loss in these organisms has been well documented, but much less is known about how compaction of microsporidia proteins affects their function. Taking a comparative genomic approach, we identified microsporidia orthologs of budding yeast proteins and show that these orthologs are enriched for essential yeast genes. We show that the median microsporidia protein is 21% shorter than its yeast counterpart and although extensive protein loss occurred after the divergence of microsporidia, reduced protein sizes were already present in microsporidian relatives. Microsporidia proteins are shorter through reduced domain lengths, diminished linker lengths, and domain loss, with 21% of microsporidia orthologs having lost domains present in yeast. On average, 34% of microsporidia orthologs have lost C-terminal residues essential for function in yeast, including 13 essential domains lost per genome. We also found that microsporidia display distinct phylogenetic patterns of domain loss, with losses occurring in a clade-specific manner. To investigate conservation of function, we used yeast complementation assays to test orthologs from several microsporidia species and their relativeRozella allomycis. These experiments reveal that most microsporidia proteins cannot complement their yeast orthologs, the ability to complement is about three-fold less than observed forR. allomycisorthologs, and proteins that do not complement are more reduced in length than their yeast orthologs. Altogether, our results demonstrate the drastic reduction of microsporidia proteins and show that these reductions have resulted in functional divergence from their fungal ancestors.
Chromatin structure and 3D architecture define differential functions ofPU.1cis regulatory elements in human blood cell lineages
Authors: Qiu Kevin , Vu Duc , Wang Leran , Bookstaver Anna , Dinh Thang N. , Goldfarb Adam N. , Tenen Daniel G. , Trinh Bon Q. 
Published: January 2024

ABSTRACTThe precise spatio-temporal expression of the hematopoietic ETS transcription factorPU.1that determines the hematopoietic cell fates is tightly regulated at the chromatin level. However, it remains elusive as to how chromatin signatures are linked to this dynamic expression patternof PU.1across blood cell lineages. Here we performed an unbiased and in-depth analysis of the relationship between humanPU.1expression, the presence of trans-acting factors, and 3D architecture at various cis-regulatory elements (CRE) proximal to thePU.1locus. We identified multiple novel CREs at the upstream region of the gene following an integrative inspection for conserved DNA elements at the chromatin-accessible regions in primary human blood lineages. We showed that a subset of CREs localize within a 10 kb-wide cluster that exhibits that exhibit molecular features of a myeloid-specific super-enhancer involved in mediatingPU.1autoregulation, including open chromatin, unmethylated DNA, histone enhancer marks, transcription of enhancer RNAs, and occupancy of the PU.1 protein itself. Importantly, we revealed the presence of common 35-kb-wide CTCF-bound insulated neighborhood that contains the CRE cluster, forming the chromatin territory for lineage-specific and CRE-mediated chromatin interactions. These include functional CRE-promoter interactions in myeloid and B cells but not in erythroid and T cells. Our findings also provide mechanistic insights into the interplay between dynamic chromatin structure and 3D architecture in defining certain CREs as enhancers or silencers in chromatin regulation ofPU.1expression. The study lays the groundwork for further examination ofPU.1CREs as well as epigenetic regulation in malignant hematopoiesis.
Crypto-wallets revolution! Key factors driving behavioral intention to adopt the Coinbase Wallet using mixed PLS-SEM/fsQCA methodology in the Spanish environment
Authors: Gil-Cordero Eloy , Ledesma-Chaves Pablo , Arteaga Sánchez Rocío , Mariano Ari Melo 
Published: January 2024

PurposeThe aim of this study is to examine the behavioral intention (BI) to adopt the Coinbase Wallet by Spanish users.Design/methodology/approachA survey was administered to individuals residing in Spain between March and April 2021. There were 301 questionnaires analyzed. This research applies a new predictive model based on technology acceptance model (TAM) 2, the unified theory of acceptance and use of technology (UTAUT) model, the theory of perceived risk and the commitment trust theory. A mixed partial least squares structural equation modeling (PLS-SEM)/fuzzy-set qualitative comparative analysis (fsQCA) methodology was employed for the modeling and data analysis.FindingsThe results showed that all the variables proposed have a direct and positive influence on the intention to use a Coinbase Wallet. The findings present clear directions for traders, investors and academics focused on improving their understanding of the characteristics of these markets.Originality/valueFirst, this study addresses important concerns relating to the adoption of crypto-wallets during the global pandemic. Second, this research contributes to the existing literature by adding electronic word of mouth (e-WOM), trust, web quality and perceived risk as new drivers of the intention to use the Coinbase Wallet, providing unique and innovative insights. Finally, the study offers a solid methodological contribution by integrating linear (PLS) and nonlinear (fsQCA) techniques, showing that both methodologies provide a better understanding of the problem and a more detailed awareness of the patterns of antecedent factors.
Commuting while Black: compensating differentials and Black–White wage gap in Canada
Authors: Dilmaghani Maryam 
Published: January 2024

PurposeUsing the Canadian Census of 2016, the present study examines the Black and White gap in compensating differentials for their commute to work.Design/methodology/approachThe data are from the Canadian Census of 2016. The standard Mincerian wage regression, augmented by commute-related variables and their confounders, is estimated by OLS. The estimations use sample weights and heteroscedasticity robust standard errors.FindingsIn the standard Mincerian wage regressions, Black men are found to earn non-negligibly less than White men. No such gap is found among women. When the Mincerian wage equation is augmented by commute duration and its confounders, commute duration is revealed to positively predict wages of White men and negatively associate with wages of Black men. At the same time, in the specifications including commute duration and its confounders, the coefficient for the dummy variable identifying Black men is positive with a non-negligible size. The latter pattern indicates wage discrepancies among Black men by their commute duration. Again, no difference is found between Black and White women in these estimations.Research limitations/implicationsThe main caveat is that due to data limitations, causal estimates could not be produced.Practical implicationsFor the Canadian working men, the uncovered patterns indicate both between and within race gaps in the impact of commuting on wages. Particularly, Black men seem to commute longer towards relatively lower paying jobs, while the opposite holds for their White counterparts. However, Black men who reside close to their work earn substantially more than both otherwise identical White men and Black men who live far away from their jobs. The implications for research and policy are discussed.Originality/valueThis is the first paper focused on commute compensating differentials by race using Canadian data.
Belt and Road Initiative: legal mechanisms to recover stolen assets
Authors: Tan Veltrice 
Published: January 2024

Purpose
This paper aims to determine the types of legal mechanisms that authorities can use to recover stolen assets for and from China.

Design/methodology/approach
Newspaper articles and books are examined as are relevant reports by various regulatory authorities and academic institutions.

Findings
The effectiveness of legal mechanisms in the recovery of stolen assets may be affected by issues such as the difficulties in tracing illicit funds, the ambiguous nature of “value” as well as the rise in technology.

Research limitations/implications
There are limited data available in relation to the prevalence of corrupt officials along the Belt and Road Initiative and the statistical success in the recovery of stolen assets. Any discussions within this paper are based on the impressionistic observations of this author, which may not reflect the true state of affairs of the Belt and Road Initiative.

Practical implications
Those who are interested in examining how authorities could recover stolen assets from and for China will have an interest in this topic.

Originality/value
The value of the paper is to demonstrate the difficulties in recovering stolen assets for and from China.
Land use determines Mediterranean ecosystems' multifunctionality more than plant richness or habitat composition
Authors: Lopezosa Paula , Soliveres Santiago , Serra Lluís , Constán‐Nava Soraya , Berdugo Miguel 
Published: January 2024

Abstract

Local and landscape diversity loss, habitat fragmentation and land‐use changes commonly co‐occur and impair ecosystem multifunctionality, yet they are often studied in isolation. Therefore, we ignore the relative importance of these drivers of ecosystem change or whether or not they interact to determine ecosystem functioning.

We measured how changes in local (plant richness) and landscape (different land uses) diversity, land use (orchards, shrubland, pine, oak and mixed forests) and habitat sise, and their interactions, affected the functioning of Mediterranean ecosystems. At 49 plots, we measured 17 above‐ and below‐ground functions, related to nutrient cycling, carbon sequestration and biotic interactions. Additionally, we generated different combinations of plots to compose artificial landscapes where multifunctionality and biodiversity conservation can be maximised, in order to aid land managers to preserve or design functional and diverse areas.

The relative importance of local and landscape attributes varied slightly depending on the target function, yet land use was by far the strongest predictor of most functions and multifunctionality above local plant biodiversity, habitat sise or landscape diversity. Oak and mixed forest were the most multifunctional land uses but were functionally wcomplemented by other land uses that maximised some individual functions.

The relative proportion of each land use within optimal landscapes varied if the target was biodiversity conservation (with an even dominance of land uses), carbon stocks or multifunctionality (highly dominated by native oak and mixed forests).

Synthesis and applications: Our results highlight the importance of remnant native forest to provide multiple ecosystem functions and the potential to restore them and complement these uses with sustainable agriculture. By merging landscape and ecosystem approaches we provide specific numbers regarding the proportion that each land use should have in order to maximise biodiversity conservation and/or functioning in these charismatic environments.
Stachydrine represses the proliferation and enhances cell cycle arrest and apoptosis of breast cancer cells via PLA2G2A/DCN axis
Authors: Zhai Zhen , Mu Tianlong , Zhao Lina , Zhu Dongsheng , Zhong Xin , Li Yiliang , Liang Chen , Li Wei , Zhou Qingyuan 
Published: January 2024

AbstractConsidering the therapeutic efficacy of Stachydrine on breast cancer (BC), this study aims to decipher the relevant mechanism. The effects of Stachydrine on BC cell viability, proliferation and apoptosis were firstly investigated. Then, Bioinformatics was applied to sort out the candidate interacting with Stachydrine as well as its expression and downstream target in BC. Relative expressions of genes of interest as well as proliferation‐ and apoptosis‐related factors in BC cells were quantified through quantitative reverse‐transcription PCR and western blot as appropriate. As a result, Stachydrine inhibited the proliferation, down‐regulated the expressions of proliferating cell nuclear antigen and CyclinD1, enhanced cell cycle arrest and apoptosis, and up‐regulated the levels of Cleaved caspase‐3 and Cleaved caspase‐9 in BC cells. Phospholipase A2 Group IIA (PLA2G2A) was predicted as the candidate interacting with Stachydrine and to be lowly expressed in BC. PLA2G2A silencing reversed while PLA2G2A overexpression reinforced the effects of Stachydrine. Decorin (DCN) was the downstream target of PLA2G2A and also lowly expressed in BC. PLA2G2A silencing counteracted yet overexpressed PLA2G2A strengthened the promoting effects of Stachydrine on DCN level. Collectively, Stachydrine inhibits the growth of BC cells to promote cell cycle arrest and apoptosis via PLA2G2A/DCN axis.
Extracellular α‐synuclein impairs sphingosine 1‐phosphate receptor type 3 (S1PR3)‐regulated lysosomal delivery of cathepsin D in HeLa cells
Authors: Nishida Susumu , Matovelo Shubi Ambwene , Kajimoto Taketoshi , Nakamura Shun‐ichi , Okada Taro 
Published: January 2024

Abstractα‐Synuclein (α‐Syn)‐positive intracellular fibrillar protein deposits, known as Lewy bodies, are thought to be involved in the pathogenesis of Parkinson's disease (PD). Although recent lines of evidence suggested that extracellular α‐Syn secreted from pathogenic neurons contributes to the propagation of PD pathology, the precise mechanism of action remains unclear. We have reported that extracellular α‐Syn caused sphingosine 1‐phosphate (S1P) receptor type 1 (S1PR1) uncoupled from Gi and inhibited downstream G‐protein signaling in SH‐SY5Y cells, although its patho/physiological role remains to be clarified. Here we show that extracellular α‐Syn caused S1P receptor type 3 (S1PR3) uncoupled from G protein in HeLa cells. Further studies indicated that α‐Syn treatment reduced cathepsin D activity while enhancing the secretion of immature pro‐cathepsin D into cell culture medium, suggesting that lysosomal delivery of cathepsin D was disturbed. Actually, extracellular α‐Syn attenuated the retrograde trafficking of insulin‐like growth factor‐II/mannose 6‐phosphate (IGF‐II/M6P) receptor, which is under the regulation of S1PR3. These findings shed light on the understanding of dissemination of the PD pathology, that is, the mechanism underlying how extracellular α‐Syn secreted from pathogenic cells causes lysosomal dysfunction of the neighboring healthy cells, leading to propagation of the disease.
Safety and dose‐finding trial of tadalafil administered for fetus in labor: A phase I clinical study
Authors: Tamaishi Yuya , Tanaka Hiroaki , Hirai Toshinori , Hiramatsu Shun‐ichi , Takakura Sho , Magawa Shoichi , Tanaka Kayo , Kondo Eiji , Iwamoto Takuya , Ikeda Tomoaki 
Published: January 2024

AbstractAimThis study aimed to investigate the safety and efficacy of tadalafil in protecting the fetus from hypoxic stress caused by repeated labor pains during delivery and preventing fetal hypoxic–ischemic encephalopathy.MethodsThe study used a three‐case cohort approach. Three patients were administered 10 mg tadalafil and monitored for serious adverse events. In the absence of serious tadalafil‐associated adverse events as assessed by the Safety Evaluation Committee, three new patients were added to the study and treated with 20 mg/dose. The blood levels of tadalafil were recorded before and after 2, 4, 8, and 12 h of administration and 2 h after delivery.ResultsA total of seven patients were enrolled, and after excluding one patient who delivered before 37 weeks, tadalafil was administered to six patients. Maternal adverse events were considered acceptable from the maternal perspective, with grade 1 headache, anorexia, and myalgia and no obstetrical complications after delivery at both doses. No serious neonatal adverse events were associated with tadalafil. Tadalafil blood levels remained stable at both doses. In addition, the level of soluble fms‐like tyrosine kinase‐1 did not alter, while that of the placental growth factor differed significantly before and after tadalafil administration.ConclusionsThe study confirmed the safety of tadalafil administration during delivery for both mothers and newborns. The stable tadalafil blood levels confirmed the efficacy of the tested administration regime at 12 h interval. These findings would assist in conducting phase II trials to further verify the optimal dose and safety of tadalafil.
Identification of new yeast strains, Candida zeylanoidesY12‐3 and Hyphopichia pseudoburtoniiY12‐1, from the intestinal tract of rainbow trout, Oncorhynchus mykiss, with potential probiotic characteristics
Authors: Çayli Bektaş Özge , Didinen Behire Işıl , Onuk Ertan Emek , Yilmaz Sevdan , Abdel‐Latif Hany M. R. 
Published: January 2024

AbstractIn this study, 2 yeasts, Candida zeylanoides isolate Y12‐3 (MN073455.1) and Hyphopichia pseudoburtonii isolate Y12‐1 (MN073489.1), were isolated from rainbow trout hindguts. Their identity was confirmed by amplification of internal transcribed spacer (ITS) gene regions. Their in vitro probiotic properties showed that they were hydrophobic and did not inhibit bacterial growth. However, they displayed positive co‐aggregation with several bacterial pathogens. It was interesting that Y12‐1 and Y12‐3 isolates survived and grew well in bile salt concentrations ranging from 0.6% to 1.5% and at low pH conditions. After a 35‐day feeding trial, the results of dietary incorporation of the yeast isolates showed that serum myeloperoxidase activity was unchanged in the treated and control groups. Meanwhile, serum lysozyme activity in yeast groups was decreased significantly compared to the control. However, fish fed with Y12‐1 had higher total protein, albumin, and globulin than other groups. Total cholesterol levels were decreased significantly in yeast groups compared to the control. Interestingly, the Y12‐1 and Y12‐3 groups showed higher survival (69.05% and 80.95%) after the challenge with Lactococcus garvieae compared to the control (45.24%). In brief, the aforementioned findings showed that Y12‐1 and Y12‐3 strains could be potential probiotic candidates for use in rainbow trout farming.
How well do workplace‐based assessments support summative entrustment decisions? A multi‐institutional generalisability study
Authors: Ryan Michael S. , Gielissen Katherine A. , Shin Dongho , Perera Robert A. , Gusic Maryellen , Ferenchick Gary , Ownby Allison , Cutrer William B. , Obeso Vivian , Santen Sally A. 
Published: January 2024

AbstractBackgroundAssessment of the Core Entrustable Professional Activities for Entering Residency requires direct observation through workplace‐based assessments (WBAs). Single‐institution studies have demonstrated mixed findings regarding the reliability of WBAs developed to measure student progression towards entrustment. Factors such as faculty development, rater engagement and scale selection have been suggested to improve reliability. The purpose of this investigation was to conduct a multi‐institutional generalisability study to determine the influence of specific factors on reliability of WBAs.MethodsThe authors analysed WBA data obtained for clerkship‐level students across seven institutions from 2018 to 2020. Institutions implemented a variety of strategies including selection of designated assessors, altered scales and different EPAs. Data were aggregated by these factors. Generalisability theory was then used to examine the internal structure validity evidence of the data. An unbalanced cross‐classified random‐effects model was used to decompose variance components. A phi coefficient of >0.7 was used as threshold for acceptable reliability.ResultsData from 53 565 WBAs were analysed, and a total of 77 generalisability studies were performed. Most data came from EPAs 1 (n = 17 118, 32%) 2 (n = 10 237, 19.1%), and 6 (n = 6000, 18.5%). Low variance attributed to the learner (<10%) was found for most (59/77, 76%) analyses, resulting in a relatively large number of observations required for reasonable reliability (range = 3 to >560, median = 60). Factors such as DA, scale or EPA were not consistently associated with improved reliability.ConclusionThe results from this study describe relatively low reliability in the WBAs obtained across seven sites. Generalisability for these instruments may be less dependent on factors such as faculty development, rater engagement or scale selection. When used for formative feedback, data from these instruments may be useful. However, such instruments do not consistently provide reasonable reliability to justify their use in high‐stakes summative entrustment decisions.
Peritoneal dialysis‐associated peritonitis: A case first for Aquamicrobium
Authors: Mehta Ashin , Yung Timothy , Davis Whitt , Choi Jennifer , Singh Sanjay 
Published: January 2024

AbstractAquamicrobium is an aerobic gram‐negative rod which until recently had only been isolated from wastewater and contaminated soil. In 2021, two cases of Aquamicrobium infection in humans were reported. Both were cases of endophthalmitis following cataract surgery. In this manuscript, we describe the presentation and treatment of a 56‐year‐old immunocompetent male who has peritoneal dialysis‐associated peritonitis caused by Aquamicrobium lusatiense. To our knowledge, this is the third reported case of Aquamicrobium infection in humans and the first example of this agent causing peritonitis.