bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr virus BRRF1 induces butyrophilin 2A1 in nasopharyngeal carcinoma cells via the IL-22/JAK3-STAT3 pathway
Authors: Liu Yue , Ye Zuodong , Chen Luo , Cheung Allen Ka Loon 
Published: August 2023

AbstractEpstein-Barr virus is highly associated with nasopharyngeal carcinoma (NPC) with genes expressed for tumor transformation or maintenance of viral latency, but there are certain genes that can modulate immune molecules. Butyrophilin 2A1 (BTN2A1) is an important activating protein for presenting phosphoantigen presentation for recognition by Vγ9Vδ2 T cells to achieve anti-tumor activities. We have previously shown that Vγ9Vδ2 T cells achieve efficacy against NPC when BTN2A1 and BTN3A1 are upregulated by stimulating EBV gene expression, particularly LMP1. Whilst BTN3A1 can be induced by LMP1 mediated IFN-γ/JNK/NLRC5 pathway, the viral gene that can regulate BTN2A1 remains elusive. Here, we showed that BTN2A1 expression is directly mediated by EBV BRRF1, which can trigger BTN2A1 promoter and downstream JAK3-STAT3 pathway in NPC43 cells as enlightened by RNA-seq data and verified by inhibitor experiments. Further, BRRF1 downregulated IL-22 binding protein (IL-22RA2) to complement the EBNA1-targeting probe (P4) induced IL-22 expression. These functions act in concordance to enhance the expression of BTN2A1, which likely lead to increased tumor cell killing by Vγ9Vδ2 T cells. Overall, this study elucidated a new mechanism of stimulating BTN2A1 expression in nasopharyngeal carcinoma cells by the EBV gene BRRF1.Summary statementThis study demonstrated a new function Epstein-Barr Virus BRRF1 to induce BTN2A1 in nasopharyngeal carcinoma via the IL-22/JAK3-STAT3 pathway, which potentiates Vγ9Vδ2 T cells against NPC.
Refining the pool of RNA-binding domains advances the classification and prediction of RNA-binding proteins
Authors: Wassmer Elsa , Koppàny Gergely , Hermes Malte , Diederichs Sven , Caudron-Herger Maïwen 
Published: August 2023

ABSTRACTKey PointsComprehensive analysis of RNA-related protein domains and families enriched in RNA-binding proteins (RBPs)Pan-species prediction of new RBPs, and prediction and validation of new RNA-binding domainsOnline resource with complete dataset including high-confidence human RBPs according to a new scoring systemFrom transcription to decay, RNA-binding proteins (RBPs) influence RNA metabolism. Using the RBP2GO database that combines proteome-wide RBP screens from 13 species, we investigated the RNA-binding features of 176896 proteins. By compiling published lists of RNA-binding domains (RBDs) and RNA-related protein family (Rfam) IDs with lists from the InterPro database, we analyzed the distribution of the RBDs and Rfam IDs in RBPs and non-RBPs to select RBDs and Rfam IDs that were enriched in RBPs. We also explored proteins for their content in intrinsically disordered regions (IDRs) and low complexity regions (LCRs). We found a strong positive correlation between IDRs and RBDs and a co-occurrence of specific LCRs. Our bioinformatic analysis indicated that RBDs/Rfam IDs were strong indicators of the RNA-binding potential of proteins and helped predicting new RBP candidates, especially in less investigated species. By further analyzing RBPs without RBD, we predicted new RBDs that were validated by RNA-bound peptides. Finally, we created the RBP2GO composite score by combining the RBP2GO score with new quality factors linked to RBDs and Rfam IDs. Based on the RBP2GO composite score, we compiled a list of 2018 high-confidence human RBPs. The knowledge collected here was integrated into the RBP2GO database athttps://RBP2GO-2-Beta.dkfz.de.GRAPHICAL ABSTRACT
Altering the substitution and crosslinking of glucuronoarabinoxylans affects cell wall porosity and assembly inBrachypodium distachyon
Authors: Tryfona Theodora , Pankratova Yanina , Petrik Deborah , Rebaque Moran Diego , Wightman Raymond , Echevarria Poza Alberto , Yu Xiaolan , Deralia Parveen Kumar , Vilaplana Francisco , Anderson Charles T. , Hong Mei , Dupree Paul 
Published: August 2023

SummaryThe Poaceae family of plants provides cereal crops that are critical for human and animal nutrition and also they are an important source of biomass. Interacting plant cell wall components give rise to recalcitrance to digestion, thus understanding the wall molecular architecture is important to improve biomass properties. Xylan is the main hemicellulose in grass cell walls. Recently, we reported structural variation in grass xylans, suggesting functional specialisation and distinct interactions with cellulose and lignin. Here, we investigated the functions of these xylans by perturbing the biosynthesis of specific xylan types.We generated CRISPR/Cas9 knockout mutants inBrachypodium distachyon XAX1andGUX2genes involved in xylan biosynthesis. Using carbohydrate gel electrophoresis we identified biochemical changes in different xylan types. Saccharification, cryo-SEM, subcritical water extraction and ssNMR were used to study wall architecture.BdXAX1A andBdGUX2 enzymes modify different types of grass xylan.Brachypodiummutant walls are more porous, suggesting the xylan substitutions directed by bothBdXAX1A andGUX2 enzymes influence xylan-xylan and/or xylan-lignin interactions.Since xylan substitutions influence wall architecture and digestibility, our findings open new avenues to improve cereals for food and to use grass biomass for feed and the production of bioenergy and biomaterials.
Structural Basis for Hyperpolarization-dependent Opening of the Human HCN1 Channel
Authors: Burtscher Verena , Mount Jonathan , Cowgill John , Chang Yongchang , Bickel Kathleen , Yuan Peng , Chanda Baron 
Published: August 2023

ABSTRACTHyperpolarization and cyclic-nucleotide (HCN) activated ion channels play a critical role in generating self-propagating action potentials in pacemaking and rhythmic electrical circuits in the human body. Unlike most voltage-gated ion channels, the HCN channels activate upon membrane hyperpolarization, but the structural mechanisms underlying this gating behavior remain unclear. Here, we present cryo-electron microscopy structures of human HCN1 in Closed, Intermediate, and Open states. Our structures reveal that the inward motion of two gating charges past the charge transfer center (CTC) and concomitant tilting of the S5 helix drives the opening of the central pore. In the intermediate state structure, a single gating charge is positioned below the CTC and the pore appears closed, whereas in the open state structure, both charges move past CTC and the pore is fully open. Remarkably, the downward motion of the voltage sensor is accompanied by progressive unwinding of the inner end of S4 and S5 helices disrupting the tight gating interface that stabilizes the Closed state structure. This “melting” transition at the intracellular gating interface leads to a concerted iris-like displacement of S5 and S6 helices, resulting in pore opening. These findings reveal key structural features that are likely to underlie reversed voltage-dependence of HCN channels.
The interplay between lumen pressure and cell proliferation determines organoid morphology in a multicellular phase field model
Authors: Tanida Sakurako , Fuji Kana , Lu Linjie , Guyomar Tristan , Lee Byung Ho , Honigmann Alf , Grapin-Botton Anne , Riveline Daniel , Hiraiwa Tetsuya , Nonomura Makiko , Sano Masaki 
Published: August 2023

AbstractOrganoids are ideal systems to predict the phenotypes of organs. However, there is currently a lack of understanding regarding the generalized rules that enable use of simple cellular principles to make morphological predictions of entire organoids. Therefore, we employed a phase field model with the following basic components: the minimum conditions for the timing and volume of cell division, lumen nucleation rules, and lumenal pressure. Through our model, we could compute and generate a myriad of organoid phenotypes observed till date. We propose morphological indices necessary to characterize the shapes and construct phase diagrams and show their dependencies on proliferation time and lumen pressure. Additionally, we introduced the lumen-index parameter, which helped in examining the criteria to maintain organoids as spherical structures comprising a single layer of cells and enclosing an intact lumen. Finally, we predict a star-like organoid phenotype that did not undergo differentiation, suggesting that the volume constraint during cell division may determine the final phenotype. In summary, our approach provides researchers with guidelines to test the mechanisms of self-organization and predict the shape of organoid.Author summaryIn nature, a wide variety of organ morphologies are observed. Owing to the complexity of the process underlying the acquisition of organs’ morphology, it is challenging to investigate the mechanisms that lead to such variations. A promising approach to study these variations is the use of “computational organoid” study, which is the computational-based study of self-organizing shapes in multicellular assemblies and fluid-filled cavities called lumens that develop from a few proliferating cells. This study explores general mechanisms that dictate how various mechanical factors affect the growing self-organized multicellular assembly. We relied on computer simulations of the mathematical model called multicellular phase-field model with lumens and explored the mechanical factor effects, such as the lumen pressure while considering the time and volume conditions required for cell division. These simulations generated and categorized a wide range of organoid phenotypes based on the varying lumen pressure and cell division conditions. These phenotypes were characterized into seven distinct classes, based on the morphological index sets, including a cellular monolayer/multilayer surrounding single or multiple lumens and branch formation. These phenotypes were obtained without the assumption of differentiation. Our study elucidates the mechanisms underlying the organoid and organ formation with different shapes, thereby highlighting the significance of mechanical forces in shaping these complex biological structures.
Mouse model of atypical DAT deficiency syndrome uncovers dopamine dysfunction associated with parkinsonism and psychiatric disease
Authors: Herborg Freja , Konrad Lisa K. , Pugh Ciara , Delignat-Lavaud Benoît , Ratner Cecilia Friis , Awadallah Nora , Pino Jose A. , Berlin Frida , Rickhag Mathias , Holst Birgitte , Woldbye David , Torres Gonzalo , Trudeau Louis-Eric , Gether Ulrik 
Published: August 2023

ABSTRACTThe dopamine transporter (DAT) plays a crucial role in regulating the brain’s dopamine (DA) homeostasis. Atypical DAT deficiency syndrome (DTSD) is a disease characterized by early-onset parkinsonism and comorbid psychiatric symptoms, but the pathobiological processes that link DAT dysfunction to both parkinsonism and psychiatric symptoms are unknown. Here, we present a genetic mouse model of atypical DTDS that expresses two coding DAT variants, DAT-I312F and DAT-D421N, derived from a patient diagnosed with ADHD and parkinsonism. Phenotypic characterization of the mutant mice revealed impaired DAT function and major homeostatic changes including increased ambient extracellular DA levels, decreased evoked DA release, and reduced expression of both tyrosine hydroxylase (TH) and of DA D1/D2 receptors. This was accompanied by diminished striatal dopaminergic axonal density and a psychomotor phenotype characterized by hyperactivity, enhanced exploratory activity, and pronounced clasping. Importantly, both amphetamine and anticholinergic treatment ameliorated aberrant hyperlocomotion in the mice. Summarized, by replicating core aspects of the patient’s phenotype, the mouse model not only provides insights into the mechanisms underlying atypical DTDS but also underlines the broad relevance of DA deficits for understanding the co-morbidity between neuropsychiatric diseases and parkinsonism.ONE SENTENCE SUMMARYIn a new mouse disease model, we explore the behavioral consequences and dopaminergic dysfunction that arise from patient-derived mutations in the dopamine transporter associated with parkinsonism and co-morbid neuropsychiatric disease
Small molecule inhibitors of transcriptional Cyclin Dependent Kinases impose HIV-1 latency, presenting “block and lock” treatment strategies
Authors: Horvath Riley M. , Brumme Zabrina L. , Sadowski Ivan 
Published: August 2023

AbstractAntiretroviral therapy is not a cure for HIV-1 as viral rebound ensues immediately following discontinuation. The block and lock therapeutic strategy seeks to enforce proviral latency and durably suppress viremic reemergence in the absence of antiretroviral therapy. Transcriptional Cyclin Dependent Kinase activity regulates LTR transcription, however, the effect and therapeutic potential of inhibiting these kinases for enforcing HIV-1 latency remains unrecognized. Using newly developed small molecule inhibitors that are highly selective for either CDK7 (YKL-5-124), CDK9 (LDC000067), or CDK8/19 (Senexin A), we found that targeting any one of these kinases prevented HIV-1 expression at concentrations that showed no toxicity. Furthermore, although CDK7 inhibition induced cell cycle arrest, inhibition of CDK9 and/or CDK8/19 did not. Of particular interest, proviral latency as induced by CDK8/19 inhibition was maintained following drug removal while CDK9 inhibitor induced latency rebounded within 24 hrs of discontinuation. Our results indicate that the Mediator complex kinases, CDK8/CDK19, are attractive block and lock targets while sole disruption of P-TEFb is unlikely to be efficacious.
TAX1BP1 recruits ATG9 vesicles through SCAMP3 binding
Authors: Hama Yutaro , Kurikawa Yoshitaka , Matsui Takahide , Mizushima Noboru , Yamamoto Hayashi 
Published: August 2023

AbstractMacroautophagy is a cellular process that delivers cytoplasmic material to lysosomes for degradation via autophagosomes. It often involves the selective degradation of ubiquitinated proteins. During selective macroautophagy, five ubiquitin-binding adaptors, p62, NBR1, OPTN, NDP52, and TAX1BP1, form biomolecular condensates with ubiquitinated proteins and recruit ATG9 vesicles, which serve as the initial membrane source required for autophagosome formation. However, the molecular details underlying the cargo/adaptor-dependent recruitment of ATG9 vesicles remain unclear. Here, we show that ATG9 vesicles are recruited by three cargo adaptors: TAX1BP1, NBR1, and OPTN. We also find that ATG9A itself is not the determinant for recruitment by these cargo adaptors, and that TAX1BP1-dependent ATG9 vesicle recruitment is mediated by SCAMP3, a transmembrane protein on the ATG9 vesicles, through binding to the coiled-coil 1 domain of TAX1BP1. These findings provide mechanistic insights into the cargo/adaptor-dependent assembly of ATG9 vesicles in mammals.
Foothold selection during locomotion in uneven terrain: Results from the integration of eye tracking, motion capture, and photogrammetry
Authors: Muller Karl S , Panfili Dan , Shields Stephanie , Matthis Jonathan S , Bonnen Kathryn , Hayhoe Mary M 
Published: August 2023

AbstractRelatively little is known about the way vision is used to guide locomotion in the natural world. What visual features are used to choose paths in natural complex terrain? To answer this question, we measured eye and body movements while participants walked in natural outdoor environments. We incorporated measurements of the 3D terrain structure into our analyses and reconstructed the terrain along the walker’s path, applying photogrammetry techniques to the eyetracker’s scene camera videos. Combining these reconstructions with the walker’s body movements, we demonstrate that walkers take terrain structure into account when selecting paths through an environment. We find that they change direction to avoid taking steeper steps that involve large height changes, instead of choosing more circuitous, relatively flat paths. Our data suggest walkers plan the location of individual footholds and plan ahead to select flatter paths. These results provide evidence that locomotor behavior in natural environments is controlled by decision mechanisms that account for multiple factors, including sensory and motor information, costs, and path planning.
Stressors and job burnout of Chinese expatriate construction professionals
Authors: Abdalla Alaeldin , Li Xiaodong , Yang Fan 
Published: August 2023

PurposeBesides ensuring traditional project objectives, expatriate construction professionals (EXCPs) working on international projects face challenges adapting to unfamiliar environments with varying construction standards, work practices and cultural values. This puts them at a high risk of job burnout. Thus, this study aims to investigate the antecedents and outcomes of EXCPs' job burnout in the international construction industry.Design/methodology/approachBased on the Job demands-resource model (JD-R), a theoretical framework was developed. Industry-specific stressors and expatriate management practices were identified using a literature review and interviews. The authors then used a questionnaire survey to collect data from Chinese EXCPs. Exploratory factor analysis, confirmatory factor analysis and structural equation modeling were then utilized to test hypotheses.FindingsThe findings indicate that early-career EXCPs experience the most severe levels of job burnout. The paths analysis proved the direct and indirect mitigating effects of expatriate management practices on job burnout, and EXCP's job burnout was associated with poor job performance and decreased intention to stay in the international assignment.Originality/valueWhile prior research has explored job burnout among construction professionals working on domestic projects, little attention has been given to EXCPs and their unique challenges. This study aims to fill this critical gap in the literature by offering a unique perspective on the antecedents and outcomes of job burnout among EXCPs in international contexts and presents a significant contribution to understanding and addressing occupational health issues faced by EXCPs.
Emotion regulation research in hospitality and tourism
Authors: Hsu Cathy H.C. , Chen Nan , Zhang Shiqin 
Published: August 2023

Purpose
This paper aims to develop a comprehensive model on intra- and interpersonal emotion regulation (ER) in hospitality and tourism (H&T) service encounters.

Design/methodology/approach
A critical review and reflection of ER research from multiple disciplines was conducted. Methodologies appropriate for investigating ER were also reviewed.

Findings
A comprehensive framework was proposed to outline key influential factors, processes and consequences of intra- and interpersonal ER in service encounters in the H&T industry. Methodologies integrating advanced tools were suggested to measure complex and dynamic emotion generation and regulation processes in social interactions from a multimodal perspective.

Research limitations/implications
The researchers developed a comprehensive conceptual model on both intra- and interpersonal ER based on a critical review of the most recent psychological research on ER. Various theoretical and methodological considerations are discussed, offering H&T scholars a solid starting point to explore dynamic emotion generation and regulation processes in complex social settings. Moreover, the model provides future directions for the expansion of ER theories, which have been mostly developed and tested based on laboratory research.

Originality/value
The proposed model addresses two critical issues identified in emotion research in the H&T field: the lack of a dynamic perspective and the neglect of the social nature of emotions. Moreover, the model provides a roadmap for future research.
A role that takes its toll? The moderating role of leadership in role stress and exposure to workplace bullying
Authors: Stapinski Piotr , Bjørkelo Brita , D'Cruz Premilla , Mikkelsen Eva G. , Gamian-Wilk Malgorzata 
Published: August 2023

Purpose
The purpose of the article is to provide further evidence for the work environment hypothesis. According to the work environment hypothesis and as documented by empirical evidence, organizational factors play a crucial role in the development of workplace bullying. However, to better understand and prevent bullying at work and establish sustainable, responsible and ethical workplaces, it is crucial to understand which organizational factors are particularly important in the development of bullying and how these factors, independently and combined, act as precursors to bullying over time. One prominent theory that explains how organizational and individual factors interact is the affective events theory (AET).

Design/methodology/approach
In a two-wave, time-lagged study (N = 364), the authors apply AET to test and explain the interplay of organizational factors in the development of bullying at work.

Findings
The results revealed that supportive and fair leadership moderates the relationship between role stress and exposure to workplace bullying.

Practical implications
Knowledge of the buffering role of supportive and fair leadership practices is important when implementing organizational interventions aimed at preventing bullying at work.

Originality/value
Although previous studies have shown the general protecting effects of supportive leadership on exposure to bullying, the current study indicates that high level of supportive and fair leadership practices decreases the level of exposure to bullying, even when role ambiguity and role conflict are relatively high.
Media richness of instructor messages: how to improve student beliefs and perceptions in online course settings
Authors: Green Karen Yvonne , Huang Meng , Walker Keith S. , Wallace Steven A. , Zhao Xinlei 
Published: August 2023

PurposeThe increasing number of online courses in higher education has provided students with convenience and flexibility. However, some adverse effects also come with online learning, including negatively affecting student beliefs in themselves and their perceptions of the instructor. Both are important factors for academic success. Grounded in media richness theory, this study aims to examine the impact of medium choices by investigating instructor messages on student beliefs and perceptions in an online course.Design/methodology/approachThis study employs a survey methodology using validated items to assess university student perceptions following faculty interactions (video versus customized email).FindingsThe authors find that videos and personalized emails, using mass distribution Excel features, help increase student beliefs, including social belongingness and self-efficacy, and improve students' perceptions of the instructor and learning environment.Originality/valueThis study contributes to the literature by establishing that the richness of media of faculty messages can impact student beliefs, which in turn, may help with student success and retention. The activities used in this study are low-effort for the instructor and may have lasting effects on the students. In addition, this study fills a gap in the literature by examining multiple forms of the richness of media and their impact on multiple aspects of students' beliefs and perceptions of the instructor.