bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac4C modification
Authors: Wang Xiaochen , Li Kang , Cheng Maosheng , Xu Hao , Chen Jie , Peng Xin , Ling Rongsong , Chen Jianwen , Wan Yuehan , Ke Lixin , Zhang Caihua , Zhang Qitong , Zou Yutong , Chen Fangfang , Chen Zhi , Chen Shuang , Li Jingting , Peng Liang , Chen Qianming , Wang Cheng , Liu Qi , Chen Demeng 
Published: February 2023

AbstractNAT10 is dysregulated and plays an essential role in various types of cancers. However, the exact machenism of how NAT10 regulates cancer progression remains debatable. In this report, we show that NAT10 affects tumorigeneis mainly based on its acetylation function on tRNA. In addition, we found NAT10 regulate the ac4C of tRNA in cancer via interaction with RNPS1, which in turn protect NAT10 from degradation by E3 ubiquitin ligase ZSWIM6. We developed TRMC-seq method to compreshensively profile tRNA ac4C sites and uncovered the presence of ac4C in a broader range of tRNA isoacceptors than previous studies. Multi-omics analysis identified AP-1 signaling pathway as a major downstream mediator of NAT10. Mechanistically, we found NAT10 is responsible for the translation efficiency genes which contain higher ac4C-tRNA codon. Importantly, our genetic mouse model validated our in vitro findings of NAT10 in cancer. Our study highlights a role of NAT10 in mediating tRNA ac4C to regulate the translation and tumorigenesis of cancer.
Changes in social behaviour with alterations of MAPK3 and KCTD13/CUL3 pathways in two new outbred rat models for the 16p11.2 syndromes with autism spectrum disorders
Authors: Lorenzo Sandra Martin , Muniz Moreno Maria Del Mar , Atas Helin , Pellen Marion , Nalesso Valérie , Raffelsberger Wolfgang , Prevost Geraldine , Lindner Loic , Birling Marie-Christine , Menoret Séverine , Tesson Laurent , Negroni Luc , Concordet Jean-Paul , Anegon Ignacio , Herault Yann 
Published: February 2023

ABSTRACTCopy number variations (CNVs) of the human 16p11.2 locus are associated with several developmental/neurocognitive syndromes. Particularly, deletion and duplication of this genetic interval are found in patients with autism spectrum disorders, intellectual disability and other psychiatric traits. The high gene density associated with the region and the strong phenotypic variability of incomplete penetrance, make the study of the 16p11.2 syndromes extremely complex. To systematically study the effect of 16p11.2 CNVs and identify candidate genes and molecular mechanisms involved in the pathophysiology, mouse models were generated previously and showed learning and memory, and to some extent social deficits. To go further in understanding the social deficits caused by 16p11.2 syndromes, we engineered deletion and duplication of the homologous region to the human 16p11.2 genetic interval in two rat outbred strains, Sprague Dawley (SD) and Long Evans (LE). The 16p11.2 rat models displayed convergent defects in social behaviour and only a few cognitive defects. Interestingly major pathways affecting MAPK3 and CUL3 were found altered in the rat 16p11.2 models with additional changes in males compared to females. Altogether, the consequences of the 16p11.2 genetic region dosage on social behaviour are now found in three different species: humans, mice and rats. In addition, the rat models pointed to sexual dimorphism, with lower severity of phenotypes in rat females compared to male mutants. This phenomenon is also observed in humans. We are convinced that the two rat models will be key to further investigating social behaviour and understanding the brain mechanisms and specific brain regions that are key to controlling social behaviour.
Ormdl3 regulation of specific ceramides is dispensable for β-cell function and glucose homeostasis under obesogenic conditions
Authors: Hurley Liam D , Lee Hugo , Wade Gina , Simcox Judith , Engin Feyza 
Published: February 2023

AbstractChronic elevation of sphingolipids contributes to β-cell failure. ORMDL3 has been identified as a key regulator of sphingolipid homeostasis, however, its function in pancreatic β-cell pathophysiology remains unclear. Here, we generated a mouse model lackingOrmdl3within pancreatic β-cells (Ormdl3β-/-). We show that loss of β-cellOrmdl3does not alter glucose tolerance, insulin sensitivity, insulin secretion, islet morphology, or cellular ceramide levels on standard chow diet. When challenged with a high fat diet, whileOrmdl3β-/-mice did not exhibit any alteration in metabolic parameters or islet architecture, lipidomics analysis revealed significantly higher levels of very long chain ceramides in their islets. Taken together, our results reveal that loss ofOrmdl3alone is not sufficient to impinge upon β-cell function or whole-body glucose and insulin homeostasis, but loss ofOrmdl3does alter specific sphingolipid levels.
Crystal structures reveal the framework ofcis-acyltransferase modular polyketide synthases
Authors: Keatinge-Clay Adrian T. , Miyazawa Takeshi , Zhang Jie , Ray Katherine A. , Lutgens Joshua D. , Bista Ramesh , Lin Sally N. 
Published: February 2023

ABSTRACTAlthough the domains ofcis-acyltransferase (cis-AT) modular polyketide synthases (PKS’s) have been understood at atomic resolution for over a decade, the domain-domain interactions responsible for the architectures and activities of these giant molecular assembly lines remain largely uncharacterized. The multimeric structure of the α6β6fungal fatty acid synthase (FAS) provides 6 equivalent reaction chambers for its acyl carrier protein (ACP) domains to shuttle carbon building blocks and the growing acyl chain between surrounding, oriented enzymatic domains. The presumed homodimeric oligomerization ofcis-AT assembly lines is insufficient to provide similar reaction chambers; however, the crystal structure of a ketosynthase (KS)+AT didomain presented here and three already reported show an interaction between the AT domains appropriate for lateral multimerization. This interaction was used to construct a framework for the pikromycin PKS from its KS, AT, and docking domains that contains highly-ordered reaction chambers. Its AT domains also mediate vertical interactions, both with upstream KS domains and downstream docking domains.
Chemoproteomic Profiling Reveals that Anti-Cancer Natural Product Dankastatin B Covalently Targets Mitochondrial VDAC3
Authors: Belcher Bridget P. , Machicao Paulo A. , Tong Binqi , Ho Emily , Friedli Julia , So Brian , Bui Helen , Isobe Yosuke , Maimone Thomas J. , Nomura Daniel K. 
Published: February 2023

AbstractChlorinated gymnastatin and dankastatin alkaloids derived from the fungal strainGymnascella dankaliensishave been reported to possess significant anti-cancer activity but their mode of action is unknown. These members possess electrophilic functional groups that may undergo covalent bond formation with specific proteins to exert their biological activity. To better understand the mechanism of action of this class of natural products, we mapped the proteome-wide cysteine-reactivity of the most potent of these alkaloids, dankastatin B, using activitybased protein profiling chemoproteomic approaches. We identified a primary target of dankastatin B in breast cancer cells as cysteine C65 of the voltage-dependent anion selective channel on the outer mitochondrial membrane VDAC3. We demonstrated direct and covalent interaction of dankastatin B with VDAC3. VDAC3 knockdown conferred hyper-sensitivity to dankastatin B-mediated anti-proliferative effects in breast cancer cells indicating that VDAC3 was at least partially involved in the anti-cancer effects of this natural product. Our study reveals a potential mode of action of dankastatin B through covalent targeting of VDAC3 and highlight the utility of chemoproteomic approaches in gaining mechanistic understanding of electrophilic natural products.
Deep learning-based codon optimization with large-scale synonymous variant datasets enables generalized tunable protein expression
Authors: Constant David A. , Gutierrez Jahir M. , Sastry Anand V. , Viazzo Rebecca , Smith Nicholas R. , Hossain Jubair , Spencer David A. , Carter Hayley , Ventura Abigail B. , Louie Michael T. M. , Kohnert Christa , Consbruck Rebecca , Bennett Joshua , Crawford Kenneth A. , Sutton John M. , Morrison Anneliese , Steiger Andrea K. , Jackson Kerianne A. , Stanton Jennifer T. , Abdulhaqq Shaheed , Hannum Gregory , Meier Joshua , Weinstock Matthew , Gander Miles 
Published: February 2023

AbstractIncreasing recombinant protein expression is of broad interest in industrial biotechnology, synthetic biology, and basic research. Codon optimization is an important step in heterologous gene expression that can have dramatic effects on protein expression level. Several codon optimization strategies have been developed to enhance expression, but these are largely based on bulk usage of highly frequent codons in the host genome, and can produce unreliable results. Here, we develop deep contextual language models that learn the codon usage rules from natural protein coding sequences across members of theEnterobacteralesorder. We then fine-tune these models with over 150,000 functional expression measurements of synonymous coding sequences from three proteins to predict expression inE. coli. We find that our models recapitulate natural context-specific patterns of codon usage and can accurately predict expression levels across synonymous sequences. Finally, we show that expression predictions can generalize across proteins unseen during training, allowing forin silicodesign of gene sequences for optimal expression. Our approach provides a novel and reliable method for tuning gene expression with many potential applications in biotechnology and biomanufacturing.
Molecular architecture and platelet-activating properties of small immune complexes assembled on intact heparin and their possible involvement in heparin-induced thrombocytopenia
Authors: Yang Yang , Du Yi , Ivanov Daniil , Niu Chendi , Clare Rumi , Smith James W. , Nazy Ishac , Kaltashov Igor A. 
Published: February 2023

AbstractHeparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin leading to a reduction in circulating platelets with an increased risk of thrombosis. It is precipitated by polymerized immune complexes consisting of pathogenic antibodies that recognize a small chemokine platelet factor 4 (PF4) bound to heparin, which trigger platelet activation and a hypercoagulable state. Characterization of these immune complexes is extremely challenging due to the enormous structural heterogeneity of such macromolecular assemblies and their constituents (especially heparin). We use native mass spectrometry to characterize small immune complexes formed by PF4, heparin and monoclonal HIT-specific antibodies. Up to three PF4 tetramers can be assembled on a heparin chain, consistent with the results of molecular modeling studies showing facile polyanion wrapping along the polycationic belt on the PF4 surface. Although these assemblies can accommodate a maximum of only two antibodies, the resulting immune complexes are capable of platelet activation despite their modest size. Taken together, these studies provide further insight into molecular mechanisms of HIT and other immune disorders where anti-PF4 antibodies play a central role.
Effect of geomagnetic activity on investors and managers: evidence from the pricing and timing of disclosure of earnings news
Authors: Asthana Sharad , Kalelkar Rachana 
Published: February 2023

PurposeThis paper's purpose was to examine the impact of geomagnetic activity (GMA) on the timing and valuation of earnings information disclosed by firms every quarter.Design/methodology/approachThe authors start the analyses with a sample of 112,669 client firms from 1989 to 2018. To analyze the impact of GMA on the earnings response coefficient (ERC), the authors use the three-day cumulative abnormal returns and cumulative abnormal returns for the extended post-earnings announcement window [2, 75] as the dependent variables. The authors interact unexpected earnings (UE) with the C9 Index, an index commonly used to measure GMA and study how GMA affects the pricing of new public information. To examine the effect of GMA on the timing of disclosure of earnings news, the authors regress a variant of the GMA index on the propensity to disclose bad earnings news.FindingsThe authors find significantly lower earnings response coefficients during periods of high GMA. This effect is permanent and stock prices do not correctly incorporate the implications of earnings information over time. The authors also show that managerial behavior is affected by GMA as well and the managers are more (less) likely to release bad (good) news during periods of higher activity. Finally, the authors also find that in situations where stakeholders are likely to rely on modern technology that depends minimally on humans, the adverse impact of GMA on the pricing of earnings information is mitigated.Originality/valueThe literature on the effect of GMA on the capital market is very limited and focuses primarily on stock returns, while the behavioral finance literature focuses on circumstances like weather, temperature and sporting outcome to study how the investors' mood affects their capital market behavior. The authors add to both the literature by investigating how GMA influences investors' and managers' behaviors in the capital market.
A supply chain perspective of prefabricated housebuilding diffusion in New Zealand
Authors: Masood Rehan , Roy Krishanu , González Vicente A. , Lim James B.P. , Nasir Abdur Rehman 
Published: February 2023

PurposeGlobally, prefabrication in housebuilding has evolved as an innovative approach to attain sustainability and affordability. However, the SC, including non-producers and producers, of prefabricated housebuilding projects is still not perceptually aligned, hindering innovation diffusion. This paper investigates the contemporary industry perspective on PHB for conceptualisation, market share and growth, innovation diffusion and the producer's role in the context of New Zealand.Design/methodology/approachAn exploratory qualitative research design was chosen to learn the perceptual stance of the industry. A semi-structured survey was conducted, followed by interviews with selected supply chain participants, who were producers and non-producers and had relevant experience in the PHB industry.FindingsThis study reports the common terminologies used by supply chain members, with justification and explanation. Further, the perceived market share and growth of the PHB industry are obtained and compared with subsequent studies to determine the capability and capacity. The perception of the diffusion of PHB by type is reported to portray the overall trend of the industry. In the last, the role of producers as the suppliers of PHB projects is investigated to establish the stakeholder positional criticality.Practical implicationsThis study can help researchers and practitioners gain insight into the PHB industry from a multi-dimensional perspective. This study is a potential first step to formalise the policy, programme, strategies and action plan for the uptake of the PHB in the New Zealand.Originality/valuePHB diffusion in the supply chain perspective, considering multi-dimensional aspects, has not been considered in previous studies as government agencies produce most of the literature. This academic research establishes the theoretical linkage towards PHB diffusion and reports the current status.
Trends in financing of basic education in Ghana – a political economy analysis
Authors: Adamba Clement 
Published: February 2023

PurposeUsing a political economy framework, this paper examines the financing trend, by investigating three systematic spikes occurring between 2004 and 2016. The study aims to provide a useful review of the interaction of politics, financial decisions and educational outcomes. Additionally it provides a useful guide, especially to academics, to identify political and economic conceptualizations that will predict expenditure decision-making of political actors and to be able to provide policy advice on the future effect of such decisions on availability and accessibility of public goods.Design/methodology/approachThe paper adopts a secondary data analysis approach, drawing upon secondary data sources such as from the Ministry of Education, budget statements from the Ministry of Finance, as well as relevant policy documents. Additional information for the study was also extracted from the manifestos of the two leading political parties in Ghana – the New Patriotic Party and the National Democratic Congress and their viewpoints on financing of education in Ghana.FindingsUsing two epochal years when financing of education peaked (2008 and 2012), which coincided with election years, the trend lends itself to being interpreted as opportunistic spending. It appears to give credence to a conclusion that the increases in spending are more politically directed and nonneutral.Originality/valueThis paper fulfills an identified need to study the trend of basic education financing in Ghana, which will help policy actors make better-informed decisions with the introduction of the novel “adaptive opportunism” framework analysis tool.
Designing circular supply chains in start-up companies: evidence from Italian fashion and construction start-ups
Authors: Ciccullo Federica , Pero Margherita , Patrucco Andrea S. 
Published: February 2023

PurposeThe theory of complex adaptive systems (CASs) represents an interesting perspective to study the characteristics of circular supply chains (CSCs). In this regard, the current literature lacks evidence regarding coordination and integration mechanisms, characteristics of the environment and emerging system properties of CSCs. This paper aims to fill this gap and focuses on how and why companies design (i.e. configure and coordinate) their CSCs and what value these design choices help to create across different industries.Design/methodology/approachThe authors use a multiple case study approach and analyze data collected from a sample of five sustainable start-ups operating in the fashion and construction industries in Italy to better understand how these companies design (i.e. configure and coordinate) their CSCs.FindingsResults reveal that in the two industries under investigation, the design of CSCs built around open and closed–loop logic is triggered by the intention to solve a negative sustainability impact. The sustainability impact determines whether the value is restored within the same supply chain, in another, or inside or outside the same industry. Interestingly, start-ups appear to coordinate other CSC actors with three leading roles: (1) orchestrator, (2) integrated orchestrator and (3) circular manufacturer. The coordination role of the start-ups differs in each supply chain configuration based on the level of vertical integration of manufacturing activities.Originality/valueFrom a theoretical perspective, the authors' results expand previous supply chain management (SCM) literature by presenting an empirical analysis of the configuration and coordination of CSCs, and discussing the drivers for creating such circularity from a CAS perspective. From a managerial perspective, the authors offer a practical experience to entrepreneurs on how to transform circular and sustainable business model aspirations into CSC practices.
An analysis of barriers for successful implementation of municipal solid waste management in Beijing: an integrated DEMATEL-MMDE-ISM approach
Authors: Wang Chao , Sun Yongkang , Lim Ming K. , Ghadimi Pezhman , Azadnia Amir Hossein 
Published: February 2023

PurposeWith rapid industrialization and urbanization, municipal solid waste (MSW) management has become a serious challenge worldwide, especially in developing countries. The Beijing Municipality is a representative example of many local governments in China that are facing MSW management issues. Although there have been studies in the area of MSW management in the literature, less attention has been devoted to developing a structured framework that identifies and interprets the barriers to MSW management in megacities, especially in Beijing. Therefore, this study focuses on identifying a comprehensive list of barriers affecting the successful implementation of MSW management in Beijing.Design/methodology/approachThrough an extensive review of related literature, 12 barriers are identified and classified into five categories: government, waste, knowledge dissemination, MSW management process and market. Using an integrated approach including the decision-making trial and evaluation laboratory (DEMATEL), maximum mean de-entropy algorithm (MMDE) and interpretive structural modeling (ISM), a conceptual structural model of MSW implementation barriers is constructed to provide insights for industrial decision-makers and policymakers.FindingsThe results show that a lack of economic support from the government, imperfect MSW-related laws and regulations, the low education of residents and the lack of publicity of waste recycling knowledge are the main barriers to MSW management in Beijing. Combined with expert opinions, the paper provides suggestions and guidance to municipal authorities and industry practitioners to guide the successful implementation of MSW management.Practical implicationsThe findings of this study can provide a reference for MSW management in other metropolises in China and other developing countries.Originality/valueThis study proposes a hybrid DEMATEL-MMDE-ISM approach to resolve the subjectivity issues of the traditional ISM approach and it analyzes the barriers that hinder MSW management practices in Beijing.
Prognosis of entrepreneurial traits among agricultural undergraduate students in India using machine learning
Authors: Jarial Sapna , Verma Jayant 
Published: February 2023

PurposeThis study aimed to understand the agri-entrepreneurial traits of undergraduate university students using machine learning (ML) algorithms.Design/methodology/approachThis study used a conceptual framework of individual-level determinants of entrepreneurship and ML. The Google Survey instrument was prepared on a 5-point scale and administered to 656 students in different sections of the same class during regular virtual classrooms in 2021. The datasets were analyzed and compared using ML.FindingsEntrepreneurial traits existed among students before attending undergraduate entrepreneurship courses. Establishing strong partnerships (0.359), learning (0.347) and people-organizing ability (0.341) were promising correlated entrepreneurial traits. Female students exhibited fewer entrepreneurial traits than male students. The random forest model exhibited 60% accuracy in trait prediction against gradient boosting (58.4%), linear regression (56.8%), ridge (56.7%) and lasso regression (56.0%). Thus, the ML model appeared to be unsuitable to predict entrepreneurial traits. Quality data are important for accurate trait predictions.Research limitations/implicationsFurther studies can validate K-nearest neighbors (KNN) and support vector machine (SVM) models against random forest to support the statement that the ML model cannot be used for entrepreneurial trait prediction.Originality/valueThis research is unique because ML models, such as random forest, gradient boosting and lasso regression, are used for entrepreneurial trait prediction by agricultural domain students.