bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autolysosomal exocytosis of lipids protect neurons from ferroptosis
Authors: Ralhan Isha , Chang Jinlan , Moulton Matthew J. , Goodman Lindsey D. , Lee Nathanael Y.J. , Plummer Greg , Pasolli H. Amalia , Matthies Doreen , Bellen Hugo J. , Ioannou Maria S. 
Published: November 2022

ABSTRACTDuring oxidative stress neurons release lipids that are internalized by glia. Defects in this coordinated process play an important role in several neurodegenerative diseases. Yet, the mechanisms of lipid release and its consequences on neuronal health are unclear. Here, we demonstrate that lipid-protein particle release by autolysosome exocytosis protects neurons from ferroptosis, a form of cell death driven by lipid peroxidation. We show that during oxidative stress, peroxidated lipids and iron are released from neurons by autolysosomal exocytosis which requires the exocytic machinery; VAMP7 and syntaxin 4. We observe membrane-bound lipid-protein particles by TEM and demonstrate that these particles are released from neurons using cryoEM. Failure to release these lipid-protein particles causes lipid hydroperoxide and iron accumulation and sensitizes neurons to ferroptosis. Our results reveal how neurons protect themselves from peroxidated lipids. Given the number of brain pathologies that involve ferroptosis, defects in this pathway likely play a key role in the pathophysiology of neurodegenerative disease.SUMMARYRelease of lipid-protein particles by autolysosomal exocytosis protects neurons from ferroptosis.
Micropropagated walnut dependency on phosphate fertilization and arbuscular mycorrhiza for growth, nutrition and quality differ between rootstocks both after acclimatization andpost-acclimatization
Authors: Mortier Emma , Jacquiod Samuel , Jouve Laurent , Martin-Laurent Fabrice , Recorbet Ghislaine , Lamotte Olivier 
Published: November 2022

AbstractThe English walnut (Juglans regiaL.) is the main species cultivated for the production of edible nuts.In vitromicropropagation of walnut explants, necessary for mass propagation of high-quality walnut rootstocks, needs anex vitroacclimatization phase followed by apost-acclimatization growth in greenhouse when plantlets become photoautotrophic. However, poor survival and slow growth rates are common difficulties encountered in nurseries when establishing micropropagated walnut saplings. As many other fruit and nut bearing trees, walnut exhibits a high dependency on symbiotic soil-borne arbuscular mycorrhizal fungi for better soil nutrient acquisition and development due to a coarse root architecture that notably limits soil inorganic phosphate (Pi) uptake. In the context of rootstock production, we investigated the establishment of seven walnut rootstocks of economic interest (RG2, RG6, R17, RX1, VLACH, VX211, and WIP3) inoculated or not withRhizophagus irregularisunder two contrasting Pi fertilization regimes. We demonstrated that inoculation withR. irregularisdecreases micropropagated walnut rootstock dependency on Pi fertilization both at the acclimatization andpost-acclimatization stages, together with improving quality, sapling biomass production and nutrition of walnut rootstocks. We also showed that these benefits are rootstock-dependent, indicating that walnut mycorrhizal dependency for Pi nutrition varies between cultivars.
Ecological network analysis reveals cancer-dependent chaperone-client interaction structure and robustness in the mitochondria
Authors: Galai Geut , Rotblat Barak , Pilosof Shai 
Published: November 2022

AbstractCancer cells alter the expression levels of metabolic enzymes to fuel proliferation. The mitochondrion is a central hub of metabolic reprogramming, where multiple chaperons service hundreds of clients, forming complex chaperone-client interaction networks (CCINs). Studying (i) how network structure varies across cancer types and (ii) the influence of structure on networks’ robustness to chaperon targeting is key to developing cancer-specific drug therapy. We investigate these yet unaddressed questions using theory and methodology from network ecology. We show that CCINs are non-randomly structured across cancer types. Moreover, we identify groups of chaperones that interact with similar clients, providing specialization on clients but also redundancy in the case of chaperone removal on the other. Simulations of network robustness show that this modular structure strongly affects cancer-specific response to chaperon removal. Our results open the door for new hypotheses regarding the ecology and evolution of CCINs and can inform caner-specific drug development strategies.
Developing a temperature-inducible transcriptional rheostat inNeurospora crassa
Authors: Tabilo-Agurto Cyndi , Del Rio-Pinilla Verónica , Eltit-Villarroel Valeria , Goity Alejandra , Muñoz-Guzmán Felipe , Larrondo Luis F. 
Published: November 2022

AbstractHeat shock protein (hsp) encoding genes, part of the highly conserved Heat Shock Response (HSR), are known to be induced by thermal stress in several organisms. InNeurospora crassa, threehspgenes,hsp30, hsp70, andhsp80, have been characterized; however, the role of definedcis-elements in their response to discrete changes in temperature remains largely unexplored. To fill this gap, while also aiming to obtain a reliable fungal heat-shock inducible system, we analyzed different sections of eachhsppromoter, by assessing the expression of real-time transcriptional reporters. Whereas all three promoters, and their resected versions, were acutely induced by high temperatures, onlyhsp30displayed a broad range of expression and high tunability amply exciding other inducible promoter systems existing in Neurospora, such as Quinic acid- or light-inducible ones. As proof of concept, we employed one of these promoters to control the expression ofclr-2, which encodes for the master regulator of Neurospora cellulolytic capabilities. The resulting strain fails to grow on cellulose at 25°C, whereas it robustly grows if heat shock pulses are delivered daily. Additionally, we designed twohsp30synthetic promoters and characterized these, as well as the native promoters, to a gradient of high temperatures, yielding a wide range of responses to thermal stimuli. Thus, Neurosporahsp30-based promoters represent a new set of modular elements that can be used as a transcriptional rheostat to adjust the expression of a gene of interest or for the implementation of regulated circuitries for synthetic biology and biotechnological strategies.ImportanceTimely and dynamic response to strong temperature rises is paramount for organismal biology. At the same time, inducible promoters are a powerful tool for fungal biotechnological and synthetic biology endeavors. In this work, we analyzed the activity of severalN. crassaheat shock protein (hsp) promoters upon a wide range of temperatures, observing thathsp30exhibits remarkable sensitivity and dynamic range of expression as we chartered the response of this promoter to subtle increases in temperature, while also building synthetic promoters based onhsp30 cis-elements. As proof of concept, we analyzed the ability ofhsp30to provide tight control of a central process such as cellulose degradation. While this study provides an unprecedented description of the regulation of theN. crassa hspgenes it also contributes with a noteworthy addition to the molecular toolset of transcriptional controllers in filamentous fungi.
Rapid Adaptation of Cellular Metabolic Rate to the MicroRNA Complements of Mammals and its Relevance to the Evolution of Endothermy
Authors: Fromm Bastian , Sorger Thomas 
Published: November 2022

SUMMARYThe metabolic efficiency of mammalian cells depends on attenuation of intrinsic translation noise by microRNAs. We devised a metric of cellular metabolic rate (cMR),rMR/Mexpoptimally fit to the number of microRNA families (miRNA.Fam), that is robust to variation in mass and sensitive to body temperature, consistent with the Heat Dissipation Limit Theory of Speakman and Król (2010)1. UsingmiRNA.Famas predictor, an Ornstein-Uhlenbeck process of stabilizing selection, with an adaptive shift at the divergence of Boreoeutheria, accounted for 95% of the variation incMRacross mammals. Branchwise rates of evolution ofcMR,miRNA.Famand body temperature concurrently increased 6- to 7-fold at the divergence of Boreoeutheria, independent of mass. CellularMRvariation across placental mammals was also predicted by the sum of model conserved microRNA-target interactions, revealing an unexpected degree of integration of the microRNA-target apparatus into the energy economy of the mammalian cell.
Why Does Synergistic Activation of WASP, but Not N-WASP, by Cdc42 and PIP2Require Cdc42 Prenylation?
Authors: Dey Souvik , Zhou Huan-Xiang 
Published: November 2022

AbstractHuman WASP and N-WASP are homologous proteins that require the binding of multiple regulators, including the acidic lipid PIP2and the small GTPase Cdc42, to relieve autoinhibition before they can stimulate the initiation of actin polymerization. Autoinhibition involves intramolecular binding of the C-terminal acidic and central motifs to an upstream basic region and GTPase binding domain. Little is known about how a single intrinsically disordered protein, WASP or N-WASP, binds multiple regulators to achieve full activation. Here we used molecular dynamics simulations to characterize the binding of WASP and N-WASP with PIP2and Cdc42. In the absence of Cdc42, both WASP and N-WASP strongly associate with PIP2-containing membranes, through their basic region and also possibly through a tail portion of the N-terminal WH1 domain. The basic region also participates in Cdc42 binding, especially for WASP; consequently Cdc42 binding significantly compromises the ability of the basic region in WASP, but not N-WASP, to bind PIP2. PIP2binding to the WASP basic region is restored only when Cdc42 is prenylated at the C-terminus and tethered to the membrane. This distinction in the activation of WASP and N-WASP may contribute to their different functional roles.
Identification of novel proteins regulating lipid droplet biogenesis by reverse genetics
Authors: Mamun Md. Abdulla Al , Reza M. Abu , Islam Md Sayeedul 
Published: November 2022

AbstractLipid droplets (LDs) are storage organelles for neutral lipids. Our knowledge about fungal LD biogenesis is limited to budding yeast. Moreover, the regulation of LD in multinucleated filamentous fungi with considerable metabolic activity is unknown. Here, 19 LD-associated proteins were identified inAspergillus oryzaeusing colocalization screening of a previously established Enhanced green fluorescent protein (EGFP) fusion proteins library. Following a functional screening, 12 candidates have been identified as lipid droplet regulating (LDR) proteins, the loss of which resulted in aberrant LD biogenesis. Four LDR proteins localize to LD via the putative amphipathic helices (AHs), as demonstrated with bioinformatics, targeted mutagenesis, and imaging. Further analysis revealed that LdrA with Opi1 domain is essential for cytoplasmic and nuclear LD biogenesis via this novel AH. Phylogenetic analysis demonstrated the pattern of their evolution, which was predominantly based-on gene duplication. Our study provides substantial molecular and evolutionary insights into LD biogenesis and creates a breakthrough in using reverse genetics for identifying LD-regulating proteins.
Measuring cell-to-cell expression variability in single-cell RNA-sequencing data: a comparative analysis and applications to B cell ageing
Authors: Zheng Huiwen , Vijg Jan , Fard Atefeh Taherian , Mar Jessica Cara 
Published: November 2022

AbstractBackgroundSingle-cell RNA-sequencing (scRNA-seq) technologies enable the capture of gene expression heterogeneity and consequently cell-to-cell variability at the cell type level. Although different methods have been proposed to quantify cell-to-cell variability, it is unclear what the optimal statistical approach is, especially in light of challenging data structures that are unique to scRNA-seq data like zero inflation.ResultsIn this study, we conducted a systematic evaluation of cell-to-cell gene expression variability using 14 different variability metrics that are commonly applied to transcriptomic data. Performance was evaluated with respect to data-specific features like sparsity and sequencing platform, biological properties like gene length, and the ability to recapitulate true levels of variability based on simulation and known biological gene sets like ribosomal genes and stably expressed genes. scran had the strongest all-round performance, and this metric was then applied to investigate the changes in cell-to-cell variability that occur during ageing. Studying ageing showcases the value of cell-to-cell variability as it is a genetically-regulated program that is influenced by stochastic processes.scRNA-seq datasets from hematopoietic stem cells (HSCs) and B lymphocytes and other cell types from this differentiation lineage were used with scran to identify the genes with consistent patterns of variable and stable expression profiles during differentiation. Furthermore, to understand the regulatory relationship for genes that were differentially-variable in their expression between young and old mice, we constructed networks using transcription factors and their known targets for HSC and B lymphocyte cells. Comparisons of these networks identified a shared TFSfpi1that although was seen to increase in gene expression variability in old mice versus young in both cell types, the corresponding targets were distinct and their gene expression variability had different directions between cell types.ConclusionsThrough these analyses, we highlight the importance of capturing cell-to-cell gene expression variability in a complex biological process like differentiation and ageing, and emphasise the value and specificity of interpreting these findings at the level of individual cell types.
A novel TGF-β-responsive enhancer regulates SRC expression and epithelial–mesenchymal transition-associated cell migration
Authors: Noshita Soshi , Kubo Yuki , Kajiwara Kentaro , Okuzaki Daisuke , Nada Shigeyuki , Okada Masato 
Published: November 2022

AbstractThe non-receptor tyrosine kinase SRC is overexpressed and/or hyperactivated in various human cancers, and facilitates cancer progression by promoting invasion and metastasis. However, the mechanisms underlying SRC upregulation are poorly understood. In this study, we demonstrated that transforming growth factor-β (TGF-β) induces SRC expression at the transcriptional level by activating a novel intragenic SRC enhancer. In the human breast epithelial cell line MCF10A, TGF-β1 stimulation upregulated theSRC1Apromoter, resulting in increased SRC mRNA and protein levels. Chromatin immunoprecipitation (ChIP)-sequencing analysis revealed that SMAD complex is recruited to three enhancer regions ~15 kb upstream and downstream of theSRCpromoter, and one of them is capable of activating theSRCpromoter in response to TGF-β. In addition, JUN, which is a member of the activator protein (AP)-1 family, also localizes to the enhancer and regulates TGF-β-induced SRC expression. Furthermore, the total amount of active SRC also increased, coinciding with the TGF-β-induced SRC expression. In TGF-β-induced epithelial–mesenchymal transition (EMT), TGF-β-induced SRC upregulation plays a crucial role in EMT-associated cell migration by activating the SRC/focal adhesion kinase (FAK) circuit. Overall, these results suggest that TGF-β-induced SRC upregulation promotes cancer cell invasion and metastasis in a subset of human malignancies.
Exploring the role of learner characteristics in learners' learning environment preferences
Authors: Chaw Lee Yen , Tang Chun Meng 
Published: November 2022

PurposeThis study intends to examine whether the reasons learners like or dislike a learning environment can help explain the differences in the characteristics of the learner and whether learner characteristics can influence a learner's preference for a learning environment.Design/methodology/approachThis study adopted an exploratory sequential mixed methods research design. The study first conducted focus groups with university students to uncover their learner characteristics by examining the reasons they liked or disliked a learning environment. This was followed by a questionnaire survey to explore how these learner characteristics influenced learner inclination for a learning environment. The survey data were analysed using exploratory and confirmatory factor analysis (partial least squares structural equation modelling).FindingsThe findings showed that two types of learner characteristics, i.e. online learner characteristics and classroom learner characteristics, significantly affected learner inclination for a learning environment. Analyses also indicated that learner demographics had no major moderating effect between learner characteristics and learner inclination for a learning environment.Practical implicationsThe findings can be useful for education institutions, learning designers and academics to design engaging learning activities to better support different learning needs.Originality/valueThis study makes a novel attempt to distinguish learner characteristics based on the reasons learners like or dislike a learning environment and establishes that individual learners' characteristics play a role in influencing their preference for a specific learning environment.
Trade protection and firm innovation in China
Authors: Huang Tao 
Published: November 2022

PurposeThe author investigates the effect of trade protection on domestic firm innovation in China and explores the channel through which trade protection affects corporate innovation.Design/methodology/approachUsing a sample of Chinese A-share manufacturing companies from 2003 to 2019, the author starts with a univariate analysis by examining the innovation output after trade protection for all samples. The author uses the natural logarithm of one plus the number of trade protection cases received by the industry to which the firm belongs in a particular year to proxy for trade protection.FindingsThe author finds that trade protection significantly encourages firms’ patent application, particularly substantive patents, which is stronger in non-state-owned enterprises. Moreover, the mitigation of financial constraint is plausible channel that allows trade protection to promote innovation.Practical implicationsFor practitioners, they should seize the dividends of national policies. In the process of implementing trade protection, they should concentrate on improving their innovation level and enhancing their core competitiveness. When they are not subject to trade protection, they can also make profits and develop in the long run.Social implicationsFor policy makers, in the early stage of industry development, trade protection can be used to ease the companies’ financing constraints and improve the companies’ profits, which will help them concentrate their efforts, promote innovation and further develop. However, in the mid-term development of the industry, policy makers should reduce trade protection. Through the entry of foreign capital, companies face increased competition, which can enhance the companies’ motivation for long-term development.Originality/valueOverall, this paper sheds light on the real effects of trade protection and the determinants of innovation. First, the paper sheds light on the impact of international trade on firms’ innovation. Second, this study also contributes to the emerging literature on the effect of trade policy uncertainty on financial constraint. Third, the paper adds to the stream of literature on the drivers of innovation.
The role of openness and cultural intelligence in students' intention to study abroad
Authors: Butkovic Ana , Brkovic Irma , Buretic Ines 
Published: November 2022

PurposeHigher education performance is boosted through cross-border cooperation and increased transnational mobility of students. In addition, exchange students have better employability skills after staying abroad compared to the students' peers. A number of studies have investigated factors that determine whether a student studies abroad. In this study, the authors focused on the role of personality trait openness to experience and cultural intelligence (CI) in explaining Croatian students' experience with and/or intention to travel abroad for studying purposes.Design/methodology/approachThe authors analyzed results from 482 students (M = 22.61, standard deviation (SD) = 2.24, 66% female), of whom 35% reported that they studied abroad or intended to study abroad. They filled in The Cultural Intelligence Scale and openness facets items from the International Personality Item Pool (IPIP-300) questionnaire.FindingsThe authors conducted a hierarchical binary logistic regression analysis and found that students who were younger, had higher adventurousness and higher motivational CI were more likely to study abroad. Results of the mediation analysis showed that the association between openness to experience facet adventurousness and intention to study abroad was partially mediated by the motivational aspect of CI.Originality/valueThis study contributes to the better understanding of complex interrelations between personality traits and CI in the context of higher education internationalization processes. This study offers unique insight into the mediating role CI has in the association between personality and mobility behavior.
Unfolding design and technology for superior sales growth under moderating effect of technological environment
Authors: Parkhi Shilpa , Karande Kiran , Barge Prashant , Belal H.M. , Foropon Cyril R.H. 
Published: November 2022

PurposeFirms use design capability across the globe to compete and increase sales, e.g. Apple. However, the payoff from design know-how has been overlooked thus far. Academic research lags in this space despite the intersection of sales, technology and design in practice. This paper provides researchers and managers with implications of the interplay between design capability and technological market conditions to enhance a firm's sales.Design/methodology/approachFirms' capability design, and sales impact have been studied in this paper across different technological market conditions. Primary technological conditions of the industry under which firms operate are captured, which are technological intensity (TI), technological competitive intensity (TCI) and technological maturity (TM). Their interplay has been studied using panel data analysis, examining fixed and random effects.FindingsDesign is an important, interesting and non-imitable capacity that yields positive firm execution results. It provides an urgent differentiator and improves deal development. This study found that all four hypotheses are generally supported. The main finding is that, provided underlying technology is good, design significantly improves sales, but design alone cannot substitute for poor technology.Practical implicationsThe results of this study link the three technological environment conditions, namely, TI, TCI and TM with sales growth. The authors find that design can and does add to superior performance, provided technological excellence exists prior. But, in the absence of good technology, design alone will hinder performance.Originality/valueThis paper examines the effect of firm design capability on sales growth. The paper finds a positive moderating effect of TCI and TM but a negative moderating effect of TI. The researchers believe these aspects of the design have not been studied before.