bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative dissection of gene regulatory elements at base resolution
Authors: Chen Zeyu , Javed Nauman , Moore Molly , Wu Jingyi , Vinyard Michael , Pinello Luca , Najm Fadi J. , Bernstein Bradley E. 
Published: October 2022

SummaryAlthough vast numbers of putative gene regulatory elements have been cataloged, the sequence motifs and individual bases that underlie their functions remain largely unknown. Here we combine epigenetic perturbations, base editing, and deep learning models to dissect regulatory sequences within the exemplar immune locus encoding CD69. Focusing on a differentially accessible and acetylated upstream enhancer, we find that the complementary strategies converge on a ∼170 base interval as critical for CD69 induction in stimulated Jurkat T cells. We pinpoint individual cytosine to thymine base edits that markedly reduce element accessibility and acetylation, with corresponding reduction of CD69 expression. The most potent base edits may be explained by their effect on binding competition between the transcriptional activator GATA3 and the repressor BHLHE40. Systematic analysis of GATA and bHLH/Ebox motifs suggests that interplay between these factors plays a general role in rapid T cell transcriptional responses. Our study provides a framework for parsing gene regulatory elements in their endogenous chromatin contexts and identifying operative artificial variants.HighlightsBase editing screens and deep learning pinpoint sequences and single bases affecting immune gene expressionAn artificial C-to-T variant in a regulatory element suppresses CD69 expression by altering the balance of transcription factor bindingCompetition between GATA3 and BHLHE40 regulates inducible immune genes and T cell states
Rabbit Development as a Model for Single Cell Comparative Genomics
Authors: Ton Mai-Linh N. , Keitley Daniel , Theeuwes Bart , Guibentif Carolina , Ahnfelt-Rønne Jonas , Andreassen Thomas Kjærgaard , Calero-Nieto Fernando J. , Imaz-Rosshandler Ivan , Pijuan-Sala Blanca , Nichols Jennifer , Benito-Gutiérrez Èlia , Marioni John C. , Göttgens Berthold 
Published: October 2022

ABSTRACTBiomedical research relies heavily on the use of model organisms to gain insight into human health and development. Traditionally, the mouse has been the favored vertebrate model, due to its experimental and genetic tractability. Non-rodent embryological studies however highlight that many aspects of early mouse development, including the egg-cylinder topology of the embryo and its method of implantation, diverge from other mammals, thus complicating inferences about human development. In this study, we constructed a morphological and molecular atlas of rabbit development, which like the human embryo, develops as a flat-bilaminar disc. We report transcriptional and chromatin accessibility profiles of almost 180,000 single cells and high-resolution histology sections from embryos spanning gastrulation, implantation, amniogenesis, and early organogenesis. Using a novel computational pipeline, we compare the transcriptional landscape of rabbit and mouse at the scale of the entire organism, revealing that extra-embryonic tissues, as well as gut and PGC cell types, are highly divergent between species. Focusing on these extra-embryonic tissues, which are highly accessible in the rabbit, we characterize the gene regulatory programs underlying trophoblast differentiation and identify novel signaling interactions involving the yolk sac mesothelium during hematopoiesis. Finally, we demonstrate how the combination of both rabbit and mouse atlases can be leveraged to extract new biological insights from sparse macaque and human data. The datasets and analysis pipelines reported here set a framework for a broader cross-species approach to decipher early mammalian development, and are readily adaptable to deploy single cell comparative genomics more broadly across biomedical research.
Is the Stalk of the SARS-CoV-2 Spike Protein Druggable?
Authors: Pipitò Ludovico , Reynolds Christopher A. , Deganutti Giuseppe 
Published: October 2022

AbstractThe SARS-CoV-2 virus spike protein (SP) is the vector of the virus infectivity. The high propensity to mutate in key regions responsible for the recognition of the human angiotensinconverting enzyme 2 (hACE2) or the antibodies produced by the immune system following infection or vaccination makes subunit 1 of the SP a difficult to target and, to date, efforts have not delivered any ACE2 binding inhibitor yet. The inherent flexibility of the stalk region, within subunit S2, is key to SARS-CoV-2 high infectivity because it facilitates the receptor binding domain encounter with ACE2. Thus, it could be a valuable therapeutic target. By employing a fragment-based strategy, we computationally studied the druggability of the conserved part of the SP stalk by means of an integrated approach that combines molecular docking with high-throughput molecular dynamics simulations. Our results suggest that the druggability of the stalk is challenging and provide the structural basis for such difficulty.
Design and Immunogenicity of SARS-CoV-2 DNA vaccine encoding RBD-PVXCP fusion protein
Authors: Dormeshkin Dmitri , Katsin Mikalai , Stegantseva Maria , Golenchenko Sergey , Shapira Michail , Dubovik Simon , Lutskovich Dzmitry , Kavaleuski Anton , Meleshko Alexander 
Published: October 2022

AbstractThe potential of immune evasive mutations accumulation of the SARS-CoV-2 virus has led to its rapid spread causing over 600 million confirmed cases and more than 6.5 million confirmed deaths. Huge demand for the rapid development and deployment of low-cost and effective vaccines against emerging variants renews interest in DNA vaccine technology. Here we report a rapid generation and immunological evaluation of novel DNA vaccine candidates against Wuhan-Hu-1 and Omicron variants, based on the RBD protein fused with the Potato virus X coat protein (PVXCP). Delivery of DNA vaccines using electroporation in a two-doses regimen induced high antibody titers and profound cellular response in mice. Antibody titers induced against Omicron variant of the vaccine were sufficient for the effective protection against both the Omicron and Wuhan-Hu-1 virus infections. PVXCP protein in the vaccine construct shifted immune response to the favorable Th1-like type and provided oligomerization of RBD-PVXCP protein. A naked DNA delivery by the needle-free injection device allowed us to achieve antibody titers comparable with the mRNA-LNP delivery in rabbits. This data identifies the RBD-PVXCP DNA vaccine platform as a promising solution for robust and effective SARS-CoV-2 protection, supporting further translational study.
Differential nuclear import determines lncRNA inheritance following mitosis
Authors: Blower Michael D. , Wang Wei , Sharp Judith 
Published: October 2022

AbstractMitosis results in a dramatic reorganization of chromatin structure in order to promote chromatin compaction and segregation to daughter cells. Consequently, mitotic entry is accompanied by transcriptional silencing and removal of most chromatin-bound RNAs from chromosomes. As cells exit mitosis, chromatin rapidly decondenses and transcription restarts as waves of differential gene expression. However, little is known about the fate of chromatin-bound RNAs following cell division. Here we explored whether nuclear RNA from the previous cell cycle is present in G1 cells following mitosis. We found that half of all nuclear RNAs are inherited in a transcriptionindependent manner following mitosis. Interestingly, the snRNA U2 is efficiently inherited by G1 cells while lncRNAs NEAT1 and MALAT1 show no inheritance following mitosis. We found that the nuclear protein SAF-A, which is hypothesized to tether RNA to DNA, did not play a prominent role in nuclear RNA inheritance, indicating the mechanism for RNA inheritance may not involve RNA chaperones that have chromatin binding activity. Instead, we observe that the timing of RNA inheritance indicates a select group of nuclear RNAs are reimported into the nucleus after the nuclear envelope has reassembled. Taken together, our work demonstrates that there is a fraction of nuclear RNA from the previous cell cycle that is reimported following mitosis and suggest that mitosis may serve as a time to reset the interaction of lncRNAs with chromatin.
Board composition, ownership structure and financial distress: insights from UK FTSE 350
Authors: Gerged Ali Meftah , Yao Shaojie , Albitar Khaldoon 
Published: October 2022

PurposeThis study aims to investigate the possible implications of compliance with corporate governance (CG) provisions, including board composition and ownership structures, on the firm’s likelihood of falling into financial distress.Design/methodology/approachThe study applies a random-effects logistic regression model as a baseline analysis using a sample of 110 FTSE 350 manufacturing companies from 2014 to 2019. This technique is supported by conducting a two-stage Heckman regression model to overcome the potential existence of endogeneity problems.FindingsThe empirical evidence suggests that board composition and ownership structure are heterogeneously associated with financial distress probabilities in that they might have either reduced or increased the financial distress of the sampled firms. Specifically, board independence, board gender diversity, audit committee independence and institutional ownership negatively influence the likelihood of financial distress. In contrast, and consistent with the expectations, ownership concentration is positively attributed to financial distress, while the board size, audit committee size and managerial ownership have insignificant impacts on financial distress.Originality/valueThe study extends the existing body of knowledge by examining the collective effect of board characteristics and ownership structures on firms’ financial distress likelihood among a sample of manufacturing firms within the FTSE 350 index post the 2008 global financial crisis and following the recent CG reforms in the UK during the study period from 2014 to 2019.
Digital technology usage as a driver of servitization paths in manufacturing industries
Authors: Harrmann Lisa Katharina , Eggert Andreas , Böhm Eva 
Published: October 2022

Purpose
This study aims to conceptually propose and empirically validate a path perspective on the servitization process of manufacturing firms. It identifies a customer and an outcome path to servitization, sheds light on the pivotal role of digital technology usage for both value-creating paths and explores their financial and relational performance outcomes.

Design/methodology/approach
The authors use a mixed-method approach, combining a qualitative study with a cross-sectional survey in the USA, the UK and Germany.

Findings
Manufacturing firms choose between two generic paths to servitization, a customer and an outcome path. Digital technology usage is equally important for both value-creating paths. Progress on the outcome path has a positive effect on firms’ financial performance, whereas the customer path has an indirect effect only, fully mediated by firms’ relational performance. Customer tenure and customer’s open-mindedness are contingency variables in the digital technology usage – servitization path – firm performance framework.

Research limitations/implications
A path perspective is useful to conceptualize the servitization processes in manufacturing industries. Future research should investigate the sequential choice of servitization paths and explore its drivers and performance outcomes.

Practical implications
To create and claim superior value for their customers, managers can choose between two servitization paths, leading to differential performance outcomes. While digital technology usage is key to progress on both paths, it is particularly effective for newly acquired customers on the customer path. Suppliers should target their value-creating service offerings at open-minded customer firms to reap their full performance potential.

Originality/value
Propose and empirically validate a path-perspective on servitization. Understand the pivotal importance of digital technology usage for both servitization paths.
Managers’ attitudes toward employees with depression and organizational citizenship behaviors in the hospitality industry: assessing the mediating role of personality
Authors: Kalargyrou Valentini , Sundar Vidya , Jahani Shiva 
Published: October 2022

Purpose
This study aims to examine the individual and contextual predictors of managerial attitudes toward employees with chronic depression (EwCD) in the hospitality and tourism field, the relationship between managerial attitudes toward EwCD and levels of organizational citizenship behavior, and the mediating role of personality in this relationship.

Design/methodology/approach
Empirical data were collected through an online survey of 305 managers working in the hospitality and tourism industry in the USA. SmartPLS 3 software was used to conduct a partial least squares-structural equation modeling analysis.

Findings
Organizational and individual characteristics of managers, such as pressure to be productive in the workplace, previous experience with depression, levels of anxiety and personality characteristics, are strong predictors of attitudes toward employees with depression. Personality mediates the effect of managers’ attitudes toward organizational citizenship behavior.

Practical implications
The study provided support that managers who have experienced depression are more understanding of the needs of EwCD and, consequently, can reduce related stigma in the workplace. Likewise, open and agreeable managers who do not feel the constant pressure to showcase high performance and who score low on anxiety and high on organizational citizenship behavior can create a safe working environment free from prejudice and discrimination toward EwCD.

Originality/value
Examining depression in the hospitality and tourism industry becomes even more critical as mental health issues are increasing in the workplace. This research contributes to the hospitality and tourism literature, which seldom investigates managerial perspectives of mental illness and sheds light on the desirable managerial personality traits necessary for creating an inclusive workplace.
Service quality and store design in retail competitiveness
Authors: Faria Sílvia , Carvalho João M.S. , Vale Vera Teixeira 
Published: October 2022

PurposeThis paper aims to analyse the importance of service quality and store design as critical variables to promote differentiation and make consumers feel satisfied and committed to a retail brand. Retailers usually undervalue the store design as an element of the strategic mix. However, it may be one of the critical elements to increase retailers’ competitive advantages.Design/methodology/approachThis exploratory study was based on 349 valid responses to a questionnaire online through a snowball sampling approach analysed with structural equation modelling.FindingsThe results confirmed that customers’ service quality positively impacts their satisfaction and commitment to the retail brands. However, store design moderates the relationship between customer satisfaction and commitment. The consumers with a higher appreciation for store design presented a lower impact of satisfaction on their commitment to the retail brand. This result shows that a significant part of their satisfaction includes store design appreciation.Research limitations/implicationsThis exploratory study was restricted to the Portuguese market, and the sample resulted from a convenience snowball approach.Practical implicationsThe retailers should consider store design as an essential variable in their marketing plans to have satisfied and committed customers and be more competitive.Originality/valueResearch on consumers’ behaviour in the retail sector, including the assessment of store design, presents a great potential within the framework of consumer–brand relationship theory, but it is still under-researched. The new model presented highlights the role of store design as a moderator variable.
A vicarious learning perspective on the relationship between home-peer performance and export intensity among SMEs
Authors: Baum Matthias , Sui Sui , Malhotra Shavin 
Published: October 2022

PurposeHome-peer firms (i.e. firms from the same industry and country) noticeably influence the internationalization behavior of small-to-medium-sized enterprises (SMEs). Drawing from vicarious learning literature, the authors theorize how home-peer firms' success in export markets affects SMEs' export intensity into those markets.Design/methodology/approachThe authors test the hypotheses on a sample of 32,108 Canadian SME exporters. A Tobit model was used to examine the effect of home-peer performance and its interactions with firm age, export experience, and geographic and institutional distance on export entry intensity.FindingsThe authors find that SMEs are more likely to enter export markets with higher intensity if home-peer firms perform well in those markets. This home-peer influence is stronger when the SME lacks export experience, when the home-peer information is more recent, and when environmental uncertainty is high.Originality/valueThe study is among the first to show empirically that the performance of home-peers positively influences the export intensity of SMEs in international markets, suggesting that SMEs use this measure to inform their internationalization strategies.
Evaluating the effect of knowledge risks on sustainability: the mediating role of organizational performance
Authors: El Khatib Rabih Adib , Ali AlaaEldine Abbass 
Published: October 2022

PurposeThe purpose of this paper is to examine the links between knowledge risks, organizational performance and knowledge-intensive firms (KIFs)' sustainability.Design/methodology/approachA questionnaire was administered with a sample of 427 respondents from Lebanon. The gathered data were analyzed using SEM approach.FindingsThe empirical evidence confirms the potential role of knowledge risks in reducing the sustainability of firms. Furthermore, organizational performance was revealed to partially mediate the relationship between knowledge risks and sustainability.Practical implicationsThe study's findings inspire managers of KIFs to use effective knowledge management practices to mitigate potential knowledge risks.Originality/valueKnowledge risks and knowledge risk management are still unexplored in the literature. This paper is a pioneering study that advances the knowledge management field by emphasizing the significance of knowledge risks and their influence on the performance and sustainability of KIFs in Lebanon, a country with a culture distinct from that of Western contexts.
Is financial distress risk important for manufacturing SMEs to rebalance the short-term debt ratio?
Authors: Sardo Filipe , Serrasqueiro Zélia , Vieira Elisabete , Armada Manuel Rocha 
Published: October 2022

PurposeThis study seeks to analyse if the adjustment towards the target short-term debt ratio of small and medium-sized firms (SMEs) is related to financial distress risk.Design/methodology/approachData obtained for a sample of Portuguese manufacturing SMEs from 2010 to 2017 were analysed using the system-generalised method of moments (GMM-sys). Using the modifiedZ-Altman score, the authors classify SMEs according to their exposure to financial distress risk.FindingsManufacturing SMEs exposed to a high risk of financial distress rebalance their short-term debt ratio quicker. However, regardless of the financial distress risk level, SMEs distant from the target short-term debt ratio adjust more slowly, suggesting that transaction costs are greater than financial distress costs.Practical implicationsPolicymakers should promote the access to external sources of finance with low transaction costs for SMEs, exposed to low levels of financial distress risk, to rebalance their short-term debt ratios quicker. Distressed SMEs far from their target short-term debt ratios, but with capacity to rebalance, need government programmes to access finance with low transaction costs to rebalance their short-term debt ratios.Originality/valueThis paper contributes to deepening our understanding of how SMEs, facing financial risk, rebalance their short-term debt ratios. SMEs, facing high financial distress risk, adjust towards their target short-term debt ratios more rapidly. However, SMEs, distant from the target short-term debt ratio face higher transaction costs than financial distress costs. These firms adjust towards their target short-term debt ratios more slowly, which may aggravate the refinancing risk and, ultimately, announce bankruptcy.
Translation competence and the translation job market in Saudi Arabia: investigating recruitment practices and job-market readiness
Authors: Salamah Dania 
Published: October 2022

PurposeThe current study set out to examine the recruitment practices and job-market readiness of translators in Saudi Arabia in light of the Process in the Acquisition of Translation Competence and Evaluation (PACTE) model of translation competence (TC). The main purpose of the study was to determine the extent to which the outcomes of translator training programs are aligned with job-market requirements.Design/methodology/approachA case study was conducted adopting a mixed-methods research design to collect qualitative and quantitative data using interviews and a questionnaire. Data were also collected from the analysis of 28 translation job advertisements. The questionnaire targeted employers, while the interviews were conducted with employers and professional translators.FindingsThe findings indicate that there is a gap between the outcomes of translator training programs and the needs of the job market with a particular emphasis on the importance of developing trainee translators' job-market skills as well as their awareness of the professional practice of translation.Research limitations/implicationsThe findings of the current study are limited to the sample from which data were collected.Practical implicationsThe study has significant implications for translators and translator training in Saudi Arabia. Although the Literature, Publishing and Translation Commission and the Saudi Translators' Association were established in 2020, additional measures are needed to support the translation profession in Saudi Arabia. Such support may take the form of specialised accreditation for translator training programs as well as licensing requirements for practitioners. Implementing these measures will play a significant role in establishing benchmarks for translator training programs and promoting the integration of job-market requirements into translator training.Originality/valueAlthough TC has been examined in the Saudi context before, examining it in light of the PACTE framework sheds new light on the job-market readiness of translation program graduates and enriches the literature on the training of translators in Saudi Arabia.