bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lost in the WASH. The functional human WASH complex 1 gene is on chromosome 20
Authors: Cerdán-Vélez Daniel , Tress Michael L. 
Published: June 2023

AbstractThe WASH1 gene produces a protein that forms part of the developmentally important WASH complex. The WASH complex activates the Arp2/3 complex to initiate branched actin networks at the surface of endosomes. As a curiosity, the human reference gene set includes nine WASH1 genes. How many of these are pseudogenes and how many arebona fidecoding genes is not clear.Eight of the nine WASH1 genes reside in rearrangement and duplication-prone subtelomeric regions. Many of these subtelomeric regions had gaps in the GRCh38 human genome assembly, but the recently published T2T-CHM13 assembly from the Telomere to Telomere (T2T) Consortium has filled in the gaps. As a result, the T2T Consortium has added four new WASH1 paralogues in previously unannotated subtelomeric regions.Here we show that one of these four novel WASH1 genes,LOC124908094, is the gene most likely to produce the functional WASH1 protein. We also demonstrate that the other twelve WASH1 genes derived from a singleWASH8Ppseudogene on chromosome 12. These 12 genes include WASHC1, the gene currently annotated as the functional WASH1 gene.We proposeLOC124908094should be annotated as a coding gene and all functional information relating to theWASHC1gene on chromosome 9 should be transferred toLOC124908094. The remaining WASH1 genes, includingWASHC1, should be annotated as pseudogenes. This work confirms that the T2T assembly has added at least one functionally relevant coding gene to the human reference set. It remains to be seen whether other important coding genes are missing from the GRCh38 reference assembly.
Retrieval of developmental social memories requires activation of the adult-born granule cell-CA2 circuit in mice
Authors: Laham Blake J. , Gore Isha R. , Brown Casey J. , Gould Elizabeth 
Published: June 2023

AbstractAdult-born granule cells (abGCs) project to the CA2 region of the hippocampus, but it remains unknown how this circuit affects behavioral function. Here we show that abGC input to the CA2 of adult mice is involved in the retrieval of remote developmental memories of the mother. Ablation of abGCs impaired the ability to discriminate between a caregiving mother and a novel mother, while this ability returned after new neurons were regenerated. Chemogenetic inhibition of projections from abGCs to the CA2 also temporarily prevented the retrieval of remote mother memories. These findings were observed when abGCs were 4-6 weeks old, but not when they were 10-12 weeks old. We also found that abGCs are necessary for differential CA2 network activity, including theta-gamma coupling and sharp wave-ripples, in response to novel versus familiar social stimuli. Taken together, these findings suggest that abGCs are necessary for neuronal oscillations associated with discriminating between social stimuli, thus enabling retrieval of remote developmental memories of the mother by their adult offspring.
Genetic and transcriptomic analysis of hyphal constriction based on a novel assay method in the rice blast fungus
Authors: Cho Eunbyeol , Lee Song Hee , Jeong Minsoo , De Mandal Surajit , Park Sook-Young , Nam Seung Won , Byeun Do Gyeung , Choi Jung Kyu , Lee Yong-Hwan , Shin Jae-Ho , Jeon Junhyun 
Published: June 2023

AbstractAn ability of fungi to undergo hyphal constriction is important for fungal ecology and diseases. In the rice blast fungus,Magnaporthe oryzae, hyphal constriction is required to traverse host cell junctions through pit fields. However, little is known about genetic underpinnings of hyphal constriction, except the requirement of a mitogen-activated protein kinase, Pmk1. Here we demonstrate that a simplein vitroassay based on nitrocellulose membrane allows investigation of the genetic basis for hyphal constriction. Using the assay, we found that the constriction limit ofM. oryzaehypha lies between 0.22 and 0.3 μm, and that a histone modification might be involved in hyphal constriction. RNA-seq experiments combining our assay and Δpmk1showed that hyphal constriction relies on transcriptional changes of genes implicated primarily in membrane and cell wall-related cellular processes in Pmk1-dependent and/or Pmk1-independent manner. Furthermore, our assays with diverse fungal species suggest correlation between hyphal constriction and fungal lifestyles. Our study reveals that hyphal constriction can be induced without host-derived cues and provides molecular and evolutionary insights into a fundamental process to infection of host plant.
A survey of CIN measures across mechanistic models
Authors: Lynch Andrew R. , Bradford Shermineh , Zhou Amber S. , Oxendine Kim , Henderson Les , Horner Vanessa L. , Weaver Beth A. , Burkard Mark E. 
Published: June 2023

AbstractChromosomal instability (CIN) is the persistent reshuffling of cancer karyotypes via chromosome mis-segregation during cell division. In cancer, CIN exists at varying levels that have differential effects on tumor progression. However, mis-segregation rates remain challenging to assess in human cancer despite an array of available measures. We evaluated measures of CIN by comparing quantitative methods using specific, inducible phenotypic CIN models of chromosome bridges, pseudobipolar spindles, multipolar spindles, and polar chromosomes. For each, we measured CIN fixed and timelapse fluorescence microscopy, chromosome spreads, 6-centromere FISH, bulk transcriptomics, and single cell DNA sequencing (scDNAseq). As expected, microscopy of tumor cells in live and fixed samples correlated well (R=0.77; p<0.01) and sensitively detect CIN. Cytogenetics approaches include chromosome spreads and 6-centromere FISH, which also correlate well (R=0.77; p<0.01) but had limited sensitivity for lower rates of CIN. Bulk genomic DNA signatures and bulk transcriptomic scores, CIN70 and HET70, did not detect CIN. By contrast, single-cell DNA sequencing (scDNAseq) detects CIN with high sensitivity, and correlates very well with imaging methods (R=0.83; p<0.01). In summary, single-cell methods such as imaging, cytogenetics, and scDNAseq can measure CIN, with the latter being the most comprehensive method accessible to clinical samples. To facilitate comparison of CIN rates between phenotypes and methods, we propose a standardized unit of CIN: Mis-segregations per Diploid Division (MDD). This systematic analysis of common CIN measures highlights the superiority of single-cell methods and provides guidance for measuring CIN in the clinical setting.SignificanceCancer relies on genomic changes to drive evolution. One type of change, Chromosomal INstability (CIN), promotes plasticity and heterogeneity of chromosome sets via ongoing errors in mitosis. The rate of these errors informs patient prognosis, drug response, and risk of metastasis. However, measuring CIN in patient tissues is challenging, hindering the emergence of CIN rate as a prognostic and predictive clinical biomarker. To advance clinical measures of CIN, we quantitatively tested the relative performance of several CIN measures in tandem using four well-defined, inducible CIN models. This survey revealed poor sensitivity in several common CIN assays and highlights the primacy of single-cell approaches. Further, we propose a standard, normalized unit of CIN, permitting comparison across methods and studies.
Ground-state pluripotent stem cells are characterized by Rac1-dependent Cadherin-enriched F-actin protrusions
Authors: Liu Shiying , Meng Yue , Kanchanawong Pakorn 
Published: June 2023

AbstractPluripotent Stem Cells (PSCs) exhibit extraordinary differentiation potentials that can be propagatedin vitroand thus are commonly utilized in regenerative medicine. While different types of PSCs exist which correspond to different stages of pluripotency during embryogenesis, important aspects of their biology in terms of their cellular architecture and mechanobiology have been less well understood, thereby limiting their tissue engineering application potentials. Since the actin cytoskeleton is a primary determinant of cell mechanical properties, here we sought to investigate how the actin cytoskeleton may be differentially regulated in different states of pluripotency. Comparing ground-state naïve mESCs and the corresponding converted prime epiblast stem cells (EpiSCs), we observed the actin cytoskeleton is drastically reorganized during the naïve to prime pluripotency transition. Strikingly, we reported a distinctive actin organization that appears to be unique to the ground state mESCs, whereby the isotropic cortical networks are decorated with prominent actin-enriched structures which contain cadherin-based cell-cell junctional components, despite not locating at cell-cell junctions. We termed these structures “cadheropodia” and showed they arise from the cis-association of E-cadherin extracellular domain. Our measurements revealed that cadheropodia is under low mechanical tension and exhibits minimal calcium dependence, consistent with its putative dependence on cis-interaction. Further, we identified Rac1 as a negative regulator of cadheropodia whereby active Rac1 induces its fragmentation and dissociation of β-catenin. Taken together, we described a novel actin-based structures in the ground-state mESCs, which may have potential roles in ground-state pluripotency and serve as useful structural markers to distinguish heterogeneous population of pluripotent stem cells.
Comprehensive Characterization and Global Transcriptome Analyses of Human Fetal Liver Terminal Erythropoiesis
Authors: Han Yongshuai , Wang Shihui , Wang Yaomei , Huang Yumin , Gao Chengjie , Guo Xinhua , Chen Lixiang , Zhao Huizhi , An Xiuli 
Published: June 2023

AbstractThe fetal liver (FL) is the key erythropoietic organ during fetal development, but knowledge on human FL erythropoiesis is very limited. In this study, we sorted primary erythroblasts from FL cells and performed RNA sequencing analyses. We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis. Notably, expression of genes enriched in proteolysis and autophagy was upregulated in orthochromatic erythroblasts (OrthoE), suggesting involvement of these pathways in enucleation. We also performed RNA sequencing ofin vitrocultured erythroblasts derived from FL CD34+cells. Comparison of transcriptomes between the primary and cultured erythroblasts revealed significant differences, indicating impacts of the culture system on gene expression. Notably, lipid metabolism gene expression was increased in cultured erythroblasts. We further immortalized erythroid cell lines from FL and cord blood (CB) CD34+cells (FL-iEry and CB-iEry, respectively). FL-iEry and CB-iEry are immortalized at the proerythroblast stage and can be induced to differentiate into OrthoE, but their enucleation ability is very low. Comparison of transcriptomes between OrthoE with and without enucleation capability revealed downregulation of pathways involved in chromatin organization and mitophagy in OrthoE without enucleation capacity, indicating that defects in chromatin organization and mitophagy contribute to the inability of OrthoE to enucleate. Additionally, the expression levels ofHBE1,HBZ, andHBG2were upregulated in FL-iEry compared with CB-iEry, and this was accompanied by downregulation ofBCL11Aand upregulation ofLIN28BandIGF2BP1. Our study provides new insights into human FL erythropoiesis and rich resources for future studies.
Predicting cued and oddball visual search performance from neural representational similarity
Authors: Yeh Lu-Chun , Thorat Sushrut , Peelen Marius V. 
Published: June 2023

AbstractCapacity limitations in visual tasks can be observed when the number of task-related objects increases. An influential idea is that such capacity limitations are determined by competition at the neural level: two objects that are encoded by shared neural populations interfere more in behavior (e.g., visual search) than two objects encoded by separate neural populations. However, the neural representational similarity of objects varies across brain regions and across time, raising the question of where and when competition determines task performance. Furthermore, it is unclear whether the association between neural representational similarity and task performance is common or unique across tasks. Here, we used neural representational similarity derived from fMRI, MEG, and deep neural networks (DNN) to predict performance on two visual search tasks involving the same objects and requiring the same responses but differing in instructions: cued visual search and oddball visual search. Separate groups of human participants (both sexes) viewed the individual objects in neuroimaging experiments to establish the neural representational similarity between those objects. Results showed that performance on both search tasks could be predicted by neural representational similarity throughout the visual system (fMRI), from 80 msec after onset (MEG), and in all DNN layers. Stepwise regression analysis, however, revealed task-specific associations, with unique variability in oddball search performance predicted by early/posterior neural similarity, and unique variability in cued search task performance predicted by late/anterior neural similarity. These results reveal that capacity limitations in superficially similar visual search tasks may reflect competition at different stages of visual processing.Significance StatementVisual search for target objects is slowed down by the presence of distractors, but not all distractors are equally distracting – the more similar a distractor is to the target, the more it slows down search. Here, we used fMRI, MEG, and a deep neural network to reveal where, when, and how neural similarity between targets and distractors predicts visual search performance across two search tasks: oddball visual search (locating the different-looking object) and cued visual search (locating the cued object). Results also revealed brain regions, time points, and feature levels that predicted task-unique performance. These results provide a neural basis for similarity theories of visual search and show that this neural basis differs across visual search tasks.
CFSA: Comparative Flux Sampling Analysis as a Guide for Strain Design
Authors: van Rosmalen R.P. , Moreno-Paz S. , Duman-Özdamar Z.E. , Suarez-Diez M. 
Published: June 2023

AbstractGenome-scale metabolic models of microbial metabolism have extensively been used to guide the design of microbial cell factories, still, many of the available strain design algorithms often fail to produce a reduced list of targets for improved performance that can be implemented and validated in a step-wise manner. We present Comparative Flux Sampling Analysis (CFSA), a strain design method based on the extensive comparison of complete metabolic spaces corresponding to maximal or near-maximal growth and production phenotypes. The comparison is complemented by statistical analysis to identify reactions with altered flux that are suggested as targets for genetic interventions including up-regulations, down-regulations and gene deletions. We applied CFSA to the production of lipids byCutaneotrichosporon oleaginosusand naringenin bySaccharomyces cerevisiaeidentifying engineering targets in agreement with previous studies as well as new interventions. CFSA is an easy-to-use, robust method that suggests potential metabolic engineering targets for growth-uncoupled production that can be applied to the design of microbial cell factories.
The role of Kölliker-Fuse nucleus in breathing variability
Authors: John S. , Barnett W. , Abdala A. , Zoccal D. , Rubin J. , Molkov Y. 
Published: June 2023

AbstractThe Kölliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apneas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupneic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing.Key pointsThe Kölliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modeling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analyzing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide plausible hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.
Entrustable professional activities: a model for job activity competency framework with microcredentials
Authors: Ma Terence , Ten Cate Olle 
Published: June 2023

PurposeJob competency frameworks are based on the listing skills required for a job. The assumption is that if a candidate is presumed to have the skills, then the candidate should be able to do the job. Thus, employers hope to identify prospective employees having the required skills. However, this may differ from knowing whether the employee is ready to be trusted to do the job activities with minimal or no supervision. The authors pose the question how employers might know about the capability of prospective employees to perform the job activities for which the employees are being hired.Design/methodology/approachIn health professions education, a job activity-based framework has been developed called “entrustable professional activities” (EPAs, activities to be entrusted). This paper reviews the job activity framework and EPAs used in medical education, considering how this might support preparation for work in other sectors of the labor market.FindingsThe authors describe the EPA framework, some implementation issues and how EPAs lead to a type of microcredential being awarded to individuals as the individuals demonstrate that the individuals can be entrusted with specific job activities.Originality/valueThe focus of this paper is to demonstrate that a medical education model could potentially be adopted by other industries to provide employers with information regarding the ability of a prospective employee in performing the job activities required. Such an approach would address employer's concerns about the job readiness of potential employees.
Quality and satisfaction in female fitness centers and the moderating roles of age and income: empirical evidence from Saudi Arabia
Authors: AbouRokbah Safinaz , Salam Mohammad Asif 
Published: June 2023

PurposeFitness centers have become quotidian fundamentals. Consequently, center managers face escalating competitiveness to sustain their businesses. Saudi Arabia's Vision 2030 emphasizes quality of life and the gravitation toward healthy lifestyles. The service quality of fitness centers is an essential factor influencing customer satisfaction. Owing to the dearth of research on this topic, especially on female-only fitness centers, this study aims to investigate the factors affecting the service quality of female fitness centers in Saudi Arabia regarding satisfaction. Additionally, this study examines the moderating roles of age and income on the relationship between service quality and satisfaction.Design/methodology/approachThe Service Quality Assessment Scale (SQAS) was adopted with five of the original dimensions (staff, workout facilities, physical facilities, exercise program and locker room) and two newly added dimensions (parking and social environment). This study also investigates the moderating roles of age and income on the relationship between service quality and customer satisfaction.FindingsAll SQAS dimensions positively affected the quality of fitness centers. Furthermore, the service quality of fitness centers increased women's satisfaction, and age and income moderated the relationship between service quality and customer satisfaction.Originality/valueFitness centers are highly competitive, and this study offers insights for managers of such facilities to improve customer satisfaction.
Evolution and assessment of corporate social performance through the lens of top category journals: a theoretical structural analysis
Authors: Singh Nidhi , Kumar Surender 
Published: June 2023

PurposeThe purpose of this study is to conduct a systematic review of the literature of the studies that have examined several theoretical perspectives on corporate social performance (CSP) and identify possible future research questions based on various theoretical viewpoints.Design/methodology/approachThe study used systematic literature review analysis on a sample of 667 studies published in top A* and A category journals listed in the Australian Business Dean Council list. The present study derived articles between 1975 and 2023 from the SCOPUS database by using relevant keywords to identify research activities in CSP.FindingsThe findings suggest that many studies on CSP have been undertaken globally. But there is a lack of studies on various theoretical perspectives, including peer uncertainty evaluation, buyer–supplier sustainability links, the role of primary stakeholders (especially consumers, employees, suppliers and secondary stakeholders), the use of technology, firm-related heterogeneities, and the role of demographic and socio-economic factors. Future research areas are recommended.Research limitations/implicationsThe study investigates existing research gaps to identify possible future research questions and frameworks that can be explored to advance the research on CSP.Practical implicationsThe research also provides implications for firms in terms of understanding diverse theoretical perspectives to develop strategies to improve a firm’s social performance.Originality/value The findings are derived from a systematic review of the literature in top-category studies that examined existing theories and frameworks in the CSP domain. This highlights the importance of other understudied complementary theories, such as complexity theory, spillover theory, critical mass theory, slack theory and so on, and related variables that can improve a firm’s social performance. Evaluation of existing theoretical perspectives is not included in other review studies.