bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting axon regeneration by enhancing the non-coding function of the injury-responsive coding geneGpr151
Authors: Lee Bohm , Lee Jinyoung , Jeon Yewon , Jang Eunsoo , Oh Yeonsoo , Kim Hyemin , Kwon Minjae , Shin Jung Eun , Cho Yongcheol 
Published: February 2021

AbstractGene expression profiling in response to nerve injury has been mainly focused on protein functions of coding genes to understand mechanisms of axon regeneration and to identify targets of potential therapeutics for nerve repair. However, the protein functions of several highly injury-induced genes includingGpr151for regulating the regenerative ability remain unclear. Here we present an alternative approach focused on non-coding functions of the coding genes, which led to the identification of the non-coding function ofGpr151RNA interacting with RNA- binding proteins such as CSDE1.Gpr151promotes axon regeneration by the function of its 5’- untranslated region (5’UTR) and expression of an engineered form of the 5’UTR improves regenerative capacity in vitro and in vivo in both sciatic nerve and optic nerve injury models. Our data suggest that searching injury-induced coding genes potentially functioning by their non- coding regions is required for the RNA-based gene therapy for improving axon regeneration.
Insights into the regulatory mechanisms ofClostridioides difficilebiofilm formation
Authors: Buckley Anthony M. , Ewin Duncan , Moura Ines B. , Wilcox Mark H. , Douce Gillian R. 
Published: February 2021

AbstractMucosal biofilms play an important role in intestinal health; however, the mucosal bacterial community has been implicated in persistent infections.Clostridioides difficileis an important nosocomial pathogen, with an unacceptable high rate of recurrence following antibiotic treatment. AsC. difficileis a known biofilm producer, a property which may contribute to this suboptimal therapeutic response, we have investigated the transcriptional changes and regulatory pathways during the transition from planktonic to biofilm mode of growth. Widespread metabolic reprogramming during biofilm formation was detected, characterised by an increased usage of glycine metabolic pathways to yield key metabolites, which are used for energy production and synthesis of short chain fatty acids. We detected the expression of 107 small non-coding RNAs that appear to, in some part, regulate these pathways; however, 25 of these small RNAs were specifically expressed during biofilm formation, indicating they may play a role in regulating biofilm-specific genes. Similar toBacillus subtilis, biofilm formation is a multi-regulatory process and SinR negatively regulates biofilm formation independently of other known mechanisms. This comprehensive analysis furthers our understanding of biofilm formation inC. difficile, identifies potential targets for anti-virulence factors, and provides evidence of the link between metabolism and virulence traits.
Gene prioritization based on random walks with restarts and absorbing states, to define gene sets regulating drug pharmacodynamics from single-cell analyses
Authors: Sales-de-Queiroz Augusto , Cruz Guilherme Sales Santa , Jean-Marie Alain , Mazauric Dorian , Roux Jérémie , Cazals Frédéric 
Published: February 2021

AbstractPrioritizing genes for their role in drug sensitivity, is an important step in understanding drugs mechanisms of action and discovering new molecular targets for co-treatment. To formalize this problem, we consider two sets of genesXandPrespectively composing the predictive gene signature of sensitivity to a drug and the genes involved in its mechanism of action, as well as a protein interaction network (PPIN) containing the products ofXandPas nodes. We introduceGenetrank, a method to prioritize the genes inXfor their likelihood to regulate the genes inP.Genetrankuses asymmetric random walks with restarts, absorbing states, and a suitable renormalization scheme. Using novel so-called saturation indices, we show that the conjunction of absorbing states and renormalization yields an exploration of the PPIN which is much more progressive than that afforded by random walks with restarts only. Using MINT as underlying network, we applyGenetrankto a predictive gene signature of cancer cells sensitivity to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL), performed in single-cells. Our ranking provides biological insights on drug sensitivity and a gene set considerably enriched in genes regulating TRAIL pharmacodynamics when compared to the most significant differentially expressed genes obtained from a statistical analysis framework alone. We also introducegene expression radars, a visualization tool to assess all pairwise interactions at a glance.Genetrankis made available in the Structural Bioinformatics Library (https://sbl.inria.fr/doc/Genetrank-user-manual.html). It should prove useful for mining gene sets in conjunction with a signaling pathway, whenever other approaches yield relatively large sets of genes.
Notch-Jagged signaling complex defined by an interaction mosaic
Authors: Zeronian Matthieu R. , Klykov Oleg , de Montserrat Júlia Portell i , Konijnenberg Maria J. , Gaur Anamika , Scheltema Richard A. , Janssen Bert J.C. 
Published: February 2021

AbstractThe Notch signaling system links cellular fate to that of its neighbors, driving proliferation, apoptosis, and cell differentiation in metazoans, whereas dysfunction leads to debilitating developmental disorders and cancers. Other than a five-by-five domain complex, it is unclear how the 40 extracellular domains of the Notch1 receptor collectively engage the 19 domains of its canonical ligand Jagged1 to activate Notch1 signaling. Here, using cross-linking mass spectrometry (XL-MS), biophysical and structural techniques on the full extracellular complex and targeted sites,we identify five distinct regions, two on Notch1 and three on Jagged1, that form an interaction network.The Notch1 membrane-proximal regulatory region individually binds to the established Notch1 epidermal growth factor (EGF) 8-13 and Jagged1 C2-EGF3 activation sites, as well as to two additional Jagged1 regions, EGF 8-11 and cysteine-rich domain (CRD). XL-MS and quantitative interaction experiments show that the three Notch1 binding sites on Jagged1 also engage intramolecularly.These interactions, together with Notch1 and Jagged1 ectodomain dimensions and flexibility determined by small-angle X-ray scattering (SAXS), support the formation of backfolded architectures. Combined, the data suggest that critical Notch1 and Jagged1 regions are not distal, but engage directly to control Notch1 signaling, thereby redefining the Notch1-Jagged1 activation mechanism and indicating new routes for therapeutic applications.
The Size of the Stag Determines the Level of Cooperation
Authors: Schnell Eric , Schimmelpfennig Robin , Muthukrishna Michael 
Published: February 2021

ABSTRACTIn the last 12,000 years, human societies have scaled up from small bands to large states of millions and even billions. Many modern societies and even groups of societies cooperate on large-scale projects with relatively low levels of conflict, but the scale and intensity of cooperation varies dramatically between societies. Here we attempt to formalize dynamics that may be driving this rapid increase in cooperation and the differences we see between societies. Our model extends an N-person stag hunt to include population growth dynamics, “stags” with different sized payoffs, and competition for these stags. An increasing number of cooperators is required to access larger stags. The payoff from these stags in turn increases carrying capacity, which increases competition for the stag. As population size increases, new cooperative thresholds are attainable, and as population size shrinks, previously attainable thresholds fall out of reach. Among other predictions, we show that when a new threshold is accessible to a population, the level of cooperation will increase to reach this threshold. However, when the next threshold is out of reach, cooperation decreases as individuals refrain from costly cooperation, preferring a smaller stag. This model offers a framework for understanding the rapid increase in the scale of human cooperation and decline of violence, differences between societies, and challenges to future cooperation.
Harnessing the Power of Antibodies to Fight Bone Metastasis
Authors: Tian Zeru , Wu Ling , Yu Chenfei , Chen Yuda , Xu Zhan , Bado Igor , Loredo Axel , Wang Lushun , Wang Hai , Wu Kuan-lin , Zhang Weijie , Zhang Xiang H. -F. , Xiao Han 
Published: February 2021

AbstractOver the past 20 years, antibody-based therapies have proved to be of great value in cancer treatment. Despite the clinical success of these biopharmaceuticals, reaching targets in the bone micro-environment has proved to be difficult perhaps due to the relatively low vascularization of bone tissue and the presence of physical barriers that impair drug penetration. Here, we have used an innovative bone targeting (BonTarg) technology to generate a first-in-class bone-targeting anti-body. Moreover, we have used two xenograft models to demonstrate the enhanced therapeutic efficacy of this bone-targeting antibody against bone metastases, compared to the efficacy of traditional antibodies. Our strategy involves the use of pClick antibody conjugation technology to chemically couple the bone-targeting moiety bisphosphonate to the human epidermal growth factor receptor 2 (HER2)-specific antibody trastuzumab. Bisphosphonate modification of therapeutic antibodies results in delivery of higher conjugate concentrations to the bone metastatic niche, relative to other tissues. In both HER2-positive and negative xenograft mice models, this strategy provides enhanced inhibition of experimental bone metastases as well as multi-organ secondary metastases that arise from the bone lesions. Specific delivery of therapeutic antibodies to the bone therefore represents a promising strategy for the treatment of bone metastatic cancers and other bone diseases.
Rice NIN-LIKE PROTEIN 3 plays a significant role in nitrogen use efficiency and grain yield under nitrate-sufficient conditions
Authors: Zhang Zi-Sheng , Xia Jin-Qiu , Alfatih Alamin , Song Ying , Huang Yi-Jie , Sun Liang-Qi , Wan Guang-Yu , Wang Shi-Mei , Wang Yu-Ping , Hu Bin-Hua , Zhang Guo-Hua , Qin Peng , Li Shi-Gui , Yu Lin-Hui , Wu Jie , Xiang Cheng-Bin 
Published: February 2021

AbstractNitrogen (N) is an essential macronutrient for crop growth and yield, but excessive application of N fertilizer has caused serious environmental pollution and greatly increased the cost of agricultural production. One of the effective and economical solutions to this dilemma is to improve the N use efficiency (NUE) of crops. Although some components involved in regulating NUE have been identified, the underlying molecular mechanism remains largely elusive in rice. Here we report that the OsNLP3 (NIN-like protein 3) is an important regulator in NUE and grain yield under nitrate-sufficient conditions. Both NUE and grain yield were significantly improved by enhanced OsNLP3 expression in the field, but reduced in osnlp3 mutants. The expression of OsNLP3 responds to both nitrate and ammonium, while OsNLP3 nuclear retention is only induced by nitrate, not by ammonium. OsNLP3 regulates the expression of a set of genes involved in N transport and assimilation by directly binding to the nitrate-responsive cis-element in the promoters of these genes. Our study demonstrates that OsNLP3 is significant for the regulation of NUE and grain yield, particularly in nitrate-rich conditions, thus providing a candidate for improving NUE and grain yield in rice.
Kinetochores respond to subtle changes in the stability of microtubule attachments
Authors: Warren Jessica D. , Valles Sarah Y. , Compton Duane A. 
Published: February 2021

AbstractProper attachment of spindle microtubules to kinetochores is necessary to satisfy the spindle assembly checkpoint and ensure faithful chromosome segregation. Microtubules detach from kinetochores to correct improperly oriented attachments, and overall kinetochore-microtubule (k-MT) attachment stability is determined in response to regulatory enzymes and the activities of kinetochore-associated microtubule stabilizing and destabilizing proteins. However, it is unknown whether regulatory enzyme activity or kinetochore-associated protein localization respond to subtle changes in k-MT attachment stability. To test for this feedback response, we monitored Aurora B kinase activity and the localization of select kinetochore proteins in metaphase cells following treatments that subtly stabilize or destabilize k-MT attachments using low dose Taxol or UMK57 (an MCAK agonist), respectively. Increasing k-MT stability induced changes in the abundance of some kinetochore proteins. In contrast, reducing k-MT stability induced both increases in Aurora B kinase signaling and changes in the abundance of some kinetochore proteins. Thus, kinetochores dynamically respond to changes in the stability of their attached microtubules. This feedback control contributes to tuning k-MT attachment stability required for efficient error correction to facilitate faithful chromosome segregation.Summary StatementLive cell imaging demonstrates that kinetochore signaling responds to feedback from attached microtubules to tune their stability to ensure faithful chromosome segregation during cell division.
Identification of Maternal-Effect Genes in Zebrafish using Maternal Crispants
Authors: Moravec Cara E. , Voit Gabriella C. , Otterlee Jarred , Pelegri Francisco 
Published: February 2021

AbstractIn animals, early development is dependent on a pool of maternal factors, both RNA and proteins, which are required for basic cellular process and cell differentiation until zygotic genome activation. The role of a majority of these maternally expressed factors in adult fertility and early development is not fully understood. By exploiting the biallelic editing ability of CRISPR-Cas9 and the benefits of the zebrafish model, we identify and characterize maternal-effect genes in a single generation, using a maternal crispant technique. We validated the ability to generate biallelic mutations in the germline by creating maternal crispants that phenocopied previously characterized maternal-effect genes:motley/birc5b,tmi/prc1l, andaura/mid1ip1. Additionally, by targeting maternally expressed genes of unknown function in zebrafish, we identified two new maternal-effect zebrafish genes,kpna7andfhcd3. The genetic identity of these maternal crispants was confirmed by sequencing haploid progeny from F0 females, which allowed the sequence analysis of newly induced lesions in the maternal germ line. Analysis of the induced lesions shows minimal genetic variation within a clutch, with an average of two edited alleles per clutch. These findings are consistent with biallelic editing events occurring in germ cells or their precursors of early CRISPR-Cas9-injected embryos, leading to maternal-effect phenotypes in the offspring. Our studies show that maternal crispants allow for the effective identification and primary characterization of maternal-effect genes in a single generation, facilitating the reverse genetics analysis of maternal factors that drive embryonic development.
Managers' subtle resistance to neoliberal reforms through and by means of management accounting
Authors: Allain Elodie , Lemaire Célia , Lux Gulliver 
Published: February 2021

PurposeWithin societies in the 21st century, individuals who are embedded in a controlled context that impedes their political actions deal with the tensions they are experiencing through attempts at resistance. Several studies that examine individual infrapolitics in organizations explain how the subtle mix of compliance and resistance are constructed at the level of individual identity in a complex mechanism that both questions the system and strengthens it. However, the interplay between managers' identities and management accounting tools in this process is a topic that deserves more investigation. The aim of this article is to understand how the subtle resistance of individuals constructs neoliberal reforms through management accounting (MA).Design/methodology/approachThe authors conducted a case study on three health and social organizations two years after major reforms were implemented in the health and social services sector in Québec, a province of Canada. These reforms were part of a new public management dynamic and involved the implementation of accounting tools, here referred to as New Public Management Accounting (NPMA) tools.FindingsThe authors’ findings show how managers participate in reforms, at the same time as attempt to stem the dehumanization they generate. Managers engage in subtly resisting, for themselves and for their field professional teams, the dehumanization and identity destruction that arises from the reforms. NPMA tools are central to this process, since managers question the reforms through NPMA tools and use them to resist creatively. However, their subtle resistance can lead to the strengthening of the neoliberal dynamic of the reform.Originality/valueThe authors contribute to both the literature of infrapolitics and MA by showing the role of NPMA tools in the construction of subtle resistance. Their article enriches the MA literature by characterizing the subtle forms of resistance and showing how managers engage in creative resistance by using the managerial potential flexibility of NPMA tools. The article also outlines how NPMA tools play a role in the dialectic process of resistance, since they aid managers in resisting reform-induced dehumanization but also support managers in reinventing and reinforcing what they are trying to fight. The authors’ study also illustrates the dialectic dynamic of resistance through NPMA in all its dimensions: discursive, material and symbolic. Finally, the authors contribute to management accounting literature by showing that NPMA tools are not only the objects of neoliberalization but also the support of backstage resistance to neoliberalization.
Risks of performing arts at theater venues
Authors: Cheng Chia-Yi , Chen Shang-Ying 
Published: February 2021

PurposeThis study aims to investigate hazards in theater venues on the performance day by combining operational risk theory with a service blueprint method.Design/methodology/approachInterviews and Delphi method are applied to find the hazards, then a survey and ANOVA are followed. The study explores a profile of hazards using data from theater venues in Taiwan and examines whether employee characteristics (i.e. professional tasks, experience and working location) affect risk perception.FindingsThe study suggests a new framework represented by a 5 (types of loss events) × 6 (service systems) matrix to check operational risks. The analyses indicate two types of hazards: risk perception about performance and operations by performers and crew (RPPOPC) and audience behaviors and safety (RPABS). RPPOPC is related to the core show, but not all employees possess high RPPOPC. Seniors have relatively low RPPOPC, and frontend house employees possess insufficient RPABS. Further, front house employees, seniors and those working in municipal cities show relatively high RPPOPC in high-loss situations.Practical implicationsManagers can use the analytic framework to effectively identify operational risks in the core show operations and audience service offerings. They can promote risk perception considering employee differences and loss severity. However, the framework does not discuss the cause-and-effect relationship. Incorporating a large amount of loss experience into a risk information system would help clarify this complex relationship.Originality/valueThis study contributes to hazard mitigation in the performing arts sector, both in the peripheral services for customers and in the core show services.
Work during COVID-19: assessing the influence of job demands and resources on practical and psychological outcomes for employees
Authors: Jamal Mohd Tariq , Anwar Imran , Khan Nawab Ali , Saleem Imran 
Published: February 2021

PurposeA sudden shift of work from the office to home amid global lockdown demands exploration of factors that facilitate or obstruct remote working and their impact on practical and psychological outcomes for the employee when individual mandatorily telecommutes full-time with no prior experience of the same. Based on job demands and resources model (JD-R), the present study explores the role of certain job demands and resources on negative and positive outcomes through mediating role of strain and well-being, respectively.Design/methodology/approachA data sample of 371 IT sector employees was collected and confirmatory factor analysis model was run to assess the model fit indices, convergent and divergent validities of the data. While proposed hypotheses of the study were tested using structural equations modeling (SEM) technique.FindingsIt was found that workload pressure, task interdependence, professional isolation and family interference in work lead to exhaustion and further stress, whereas the presence of autonomy and schedule flexibility and sufficient technology resources improve employee work-life balance and further better productivity and performance and job satisfaction. Improved well-being was also found to reduce stress for full-time telecommuters.Practical implicationsThis study provides implications that will help in doing away with exhaustion and stress for employees and ensure business continuity in emergencies like COVID-19 pandemic.Originality/valueThere are no past instances of mandatory full-time telecommuting arrangement by organizations, and researchers never had the opportunity to study it. This research, based on the JD-R model provides for the first time empirical insights into the experiences of mandatory full-time telecommuting during COVID-19 induced lockdown.