bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular determinants of Karyopherin-β2 chaperone and disaggregation activity
Authors: Fare Charlotte M. , Rhine Kevin , Lam Andrew , Myong Sua , Shorter James 
Published: September 2022

AbstractKaryopherin-β2 (Kapβ2) is a nuclear-import receptor that recognizes proline-tyrosine nuclear localization signals (PY-NLSs) of diverse cytoplasmic cargo for transport to the nucleus. Kapβ2 cargo include several disease-linked RNA-binding proteins (RBPs) with prion-like domains (PrLDs), such as FUS, TAF15, EWSR1, hnRNPA1, and hnRNPA2. These RBPs with PrLDs are linked via pathology and genetics to debilitating degenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and multisystem proteinopathy (MSP). Remarkably, Kapβ2 prevents and reverses aberrant phase transitions of these cargo, which is cytoprotective. However, the molecular determinants of Kapβ2 that enable these activities remain poorly understood, particularly from the standpoint of nuclear-import receptor architecture. Kapβ2 is a superhelical protein comprised of 20 HEAT repeats. Here, we design truncated variants of Kapβ2 and assess their ability to antagonize FUS aggregation and toxicity in yeast and FUS condensation at the pure protein level and in human cells. We find that HEAT repeats 8-20 of Kapβ2 recapitulate all salient features of Kapβ2 activity. By contrast, Kapβ2 truncations lacking even a single cargo-binding HEAT repeat display reduced activity. Thus, we define a minimal Kapβ2 construct for delivery in adeno-associated viruses as a potential therapeutic for ALS/FTD, MSP, and related disorders.
Identification of genes required for long term survival of L. pneumophila in water
Authors: Aurass Philipp , Kim Seongok , Pinedo Victor , Cava Felipe , Isberg Ralph R. 
Published: September 2022

AbstractLong-term survival of Legionella pneumophila in aquatic environments is thought to be important for establishing an ecological niche necessary for epidemic outbreaks in humans. Eliminating bacterial colonization in plumbing systems is the primary strategy that depletes this reservoir and prevents disease. To uncover L. pneumophila determinants facilitating survival in water, a Tn-seq strategy was used to identify survival-defective mutants during 50-day starvation in tap water at 42°C. The mutants with most drastic survival defects carried insertions in electron transport chain genes, indicating that membrane energy charge and/or ATP synthesis requires the generation of a proton gradient by the respiratory chain to maintain survival in the presence of water stress. In addition, periplasmically-localized proteins that are known (EnhC) or hypothesized (lpg1697) to stabilize the cell wall against turnover were essential for water survival. To test that the identified mutations disrupted water survival, candidate genes were knocked down by CRISPRi. The vast majority of knockdown strains with verified transcript depletion showed remarkably low viability after 50-day incubations. To demonstrate that maintenance of cell wall integrity was an important survival determinant, a deletion mutation in lpg1697, in a gene encoding a predicted L,D-transpeptidase domain, was analyzed. The loss of this gene resulted in increased osmolar sensitivity and carbenicillin hypersensitivity relative to the WT, as predicted for loss of an L,D-transpeptidase. These results indicate that the L. pneumophila envelope has been evolutionarily selected to allow survival under conditions in which the bacteria are subjected to long-term exposure to starvation and low osmolar conditions.ImportanceWater is the primary vector for transmission of L. pneumophila to humans and the pathogen is adapted to persist in this environment for extended periods of time. Preventing survival of L. pneumophila in water is therefore critical for prevention of Legionnaire’s disease. We analyzed dense transposon mutation pools for strains with severe survival defects during a 50-day water incubation at 42°C. By tracking the associated transposon insertion sites in the genome, we defined a distinct essential gene set for water survival and demonstrate that a predicted peptidoglycan crosslinking enzyme, lpg1697, and components of the electron transport chain are required to ensure survival of the pathogen. Our results indicate that select characteristics of the cell wall and components of the respiratory chain of L. pneumophila are primary evolutionary targets being shaped to promote its survival in water.
Synaptic Competition Enhances the Discrimination of Interfering Memories
Authors: Fung Chi Chung Alan , Fukai Tomoki 
Published: September 2022

AbstractLong-term plasticity is the primary mode of synaptic weight updating. However, other updating modes include modification of synaptic connections across neurons. The synaptic competition found during adult neurogenesis is an example. In this process, adult-born neurons are integrated into the existing neuronal pool by competing with mature neurons for synaptic connections from the entorhinal cortex. Evidence suggests that adult neurogenesis is critical for discriminating similar memories, i.e., memories with considerable interferences. This computational study aims to link synaptic competition with pattern separation. We show that synaptic competition and neuronal maturation are crucial for separating considerably overlapping memory patterns. Furthermore, we demonstrate that a feed-forward neural network trained by a competition-based learning rule can outperform a multi-layer perceptron trained by the backpropagation algorithm, especially when the sample size is small. These results unveil the functional implications and potential applications of synaptic competition in neural computation.
Structural study of UFL1-UFC1 interaction uncovers the importance of UFL1 N-terminal helix for ufmylation
Authors: Banerjee Sayanika , Varga Julia K , Kumar Manoj , Zoltsman Guy , Isupov Michail N , Rosenzweig Rina , Schueler-Furman Ora , Wiener Reuven 
Published: September 2022

AbstractUfmylation, a protein modification by Ubiquitin-like (UBL) protein UFM1, plays a crucial role in several cellular processes including DNA damage response, protein translation and ER homeostasis. To date, little is known how the enzymes responsible for this modification coordinate their action. Here we have studied the details of UFL1 (E3) activity, its binding to UFC1 (E2), and its relation to UBA5 (E1), using a combination of structural modeling with Alphafold2, X-ray crystallography, NMR, andin vitrobiochemical activity assays. Guided by an Alphafold2 model, we generated an active UFL1 fusion construct that includes its cofactor DDRGK1, and solved the first crystal structure of this critical interaction. This fusion construct also unveiled the importance of the N-terminal helix of UFL1 for its binding to UFC1, which was validated by ITC and NMR experiments. Importantly, the binding site suggested by our structural model of the UFL1-UFC1 interaction reveals a conserved interface, and suggests a competition for binding to UFC1 between UFL1 and UBA5, which we reconfirmed by NMR. Altogether, our study reveals a novel, terminal helix-mediated regulatory mechanism which coordinates the cascade of E1-E2-E3 mediated transfer of UFM1 to its substrate, and provides new leads to target this important modification.Significance statementUfmylation is an important post-translational modification, but little is known about the mechanistic details of its machinery, and in particular how the UFM1 E3 ligase (UFL1) binds and functions together with the E2 conjugating enzyme (UFC1). We combined AlphaFold2 modeling, X-ray crystallography, NMR and biochemical experiments to reveal crucial elements that govern UFL1 activity and ufmylation. We discover a crucial role for the UFL1 N-terminal helix in binding to UFC1 and productive ufmylation. This helix competes with the E1 (UBA5) C-terminal helix for binding to UFC1. Altogether, our findings uncover a new, helix-mediated regulatory mechanism in ufmylation.
O-antigen diversification masks identification of highly pathogenic STEC O104:H4-like strains
Authors: Lang Christina , Fruth Angelika , Campbell Ian W. , Jenkins Claire , Smith Peyton , Strockbine Nancy , Weill François-Xavier , Nübel Ulrich , Grad Yonatan H. , Waldor Matthew K. , Flieger Antje 
Published: September 2022

AbstractShiga toxin-producingE. coli(STEC) can give rise to a range of clinical outcomes from diarrhea to the life-threatening systemic condition, hemolytic uremic syndrome (HUS). Although STEC O157:H7 is the serotype most frequently associated with HUS, a major outbreak of HUS occurred in 2011 in Germany, and was caused by a rare serotype, STEC O104:H4. Prior to 2011 and since the outbreak, STEC O104:H4 strains have only rarely been associated with human infections. From 2012 to 2020 intensified STEC surveillance was performed in Germany where subtyping of ∼8,000 clinical isolates by molecular methods including whole genome sequencing was carried out. A rare STEC serotype O181:H4 associated with HUS was identified and, like the STEC O104:H4 outbreak strain, this strain belongs to sequence type (ST) 678. Genomic and virulence comparisons revealed that the two strains are phylogenetically related and differ principally in the gene cluster encoding their respective lipopolysaccharide O-antigens but exhibit similar virulence phenotypes. In addition, five other serotypes belonging to ST678 from human clinical infection, such as OX13:H4, O127:H4, OgN-RKI9:H4, O131:H4, and O69:H4, were identified from diverse locations worldwide.ImportanceOur data suggest the high virulence ensemble of the STEC O104:H4 outbreak strain remains a global threat because genomically similar strains cause disease worldwide, but that horizontal acquisition of O-antigen gene clusters has diversified the O-antigens of strains belonging to ST678. Thus, identification of these highly pathogenic strains is masked by diverse and rare O-antigens, thereby confounding the interpretation of their potential risk.
Dentate gyrus morphogenesis is regulated by β-CATENIN function in hem-derived fimbrial glia
Authors: Parichha Arpan , Datta Debarpita , Suresh Varun , Chatterjee Mallika , Holtzman Michael J. , Tole Shubha 
Published: September 2022

AbstractThe dentate gyrus, a gateway for input to the hippocampal formation, arises from progenitors in the medial telencephalic neuroepithelium adjacent to the cortical hem. Dentate progenitors navigate a complex migratory path guided by two cell populations that arise from the hem, the fimbrial glia, and Cajal-Retzius (CR) cells. Since the hem expresses multiple Wnt genes, we examined whether β-CATENIN, which mediates canonical Wnt signaling and also participates in cell adhesion, is necessary for the development of hem-derived lineages. We report that the fimbrial glial scaffold is disorganized and CR cells are mispositioned upon hem-specific disruption of β-CATENIN. Consequently, the dentate migratory stream is severely affected, and the dentate gyrus fails to form. Using selective Cre drivers, we further determined that β-CATENIN function is required in the fimbrial glial scaffold, but not in the CR cells, for guiding the dentate migration. Our findings highlight a primary requirement for β-CATENIN for the organization of the fimbrial scaffold and a secondary role for this factor in dentate gyrus morphogenesis.
Influencing factors of Chinese consumers' purchase intention towards sustainable luxury
Authors: Yang Huaxia , Cheng Jinlong , Schaefer Allen D. , Kojo Shion 
Published: September 2022

PurposeThe authors examined the influence of perceived value on consumer attitude and purchase intention (PI) and the relationship between attitude and PI towards sustainable luxury products (SLP) in China.Design/methodology/approachAn online survey was conducted with 935 consumers of luxury fashion in mainland China. Structural equation modelling was applied to measure and analyse the relationship between values (i.e. hedonic values, social values, and value for money) and consumer attitude and PI.FindingsConsumers' multidimensional values positively affected their attitude. Social values and value for money had a significant positive effect on PI towards SLP. However, hedonic values had no effect on PI.Research limitations/implicationsThe sample was drawn from first-tier cities in China, and the results cannot be generalised. The authors examined three dimensions of consumption values. Future research should consider additional markets, values, and influencing factors.Practical implicationsLuxury companies should understand Chinese consumers' diverse values and develop sustainable products that meet consumers' principles. These principles increase the perceived value of the products and thereby guide luxury brands to make marketing strategies to increase sales.Originality/valueThis is the first empirical study to use the theory of perceived value scale (PERVAL) to understand consumer behaviour regarding SLP in China.
Analysts’ long-term growth forecasts and the post-earnings-announcement drift
Authors: He Shuoyuan 
Published: September 2022

PurposeThis study examines the relation between the presence of analysts’ long-term growth (LTG) forecasts and the post-earnings-announcement drift (PEAD).Design/methodology/approachUsing a sample of firm-quarters from 1995 to 2013, the author conducts various regression analyses.FindingsThe author finds that the magnitude of PEAD is significantly smaller for firms with LTG forecasts. The relationship holds after controlling for a wide range of explanatory variables for PEAD returns or for the presence of LTG forecasts. The author further investigates three nonexclusive hypotheses to explain this relationship. First, LTG forecasts may convey incremental value-relevant information that facilitates investors’ processing of short-term earnings information. Second, the presence of LTG forecasts may indicate superiority in analysts’ short-term forecast ability and identify firms with more efficient short-term forecasts. Third, the presence of LTG forecasts may be associated with cross-sectional differences in the persistence of earnings surprises. The author finds that none of these fully accounts for the negative relationship between the presence of LTG forecasts and PEAD returns. Instead, the relationship may be a result of the presence of LTG forecasts capturing some unobservable firm characteristics beyond those identified in prior studies.Originality/valueThis study contributes to the PEAD literature by identifying a novel analyst-based predictor of the cross-sectional variation in PEAD returns.
Determinants of smallholder farmers' membership in co-operative societies: evidence from rural Kenya
Authors: Miroro Obadia Okinda , Anyona Douglas Nyambane , Nyamongo Isaac , Bukachi Salome A. , Chemuliti Judith , Waweru Kennedy , Kiganane Lucy 
Published: September 2022

PurposeDespite the potential for co-operatives to improve smallholder farmers' livelihoods, membership in the co-operatives is low. This study examines factors that influence smallholder farmers' decisions to join agricultural co-operatives.Design/methodology/approachThis study involved a survey of 1,274 smallholder chicken farmers. The data were analysed through a two-sample t-test of association, Pearson's Chi-square test and binary probit regression model.FindingsThe results suggest that farming as the main source of income, owning a chicken house, education attainment, attending training or accessing information, vaccination of goats and keeping a larger herd of goats are the key factors which significantly influence co-operative membership. However, gender, age, household size, distance to the nearest agrovet, vaccinating chicken and the number of chickens kept do not influence co-operative membership.Research limitations/implicationsThe survey did not capture data on some variables which have been shown to influence co-operative membership. Nevertheless, the results show key explanatory variables which influence membership in co-operatives.Practical implicationsThese findings have implications for development agencies that seek to use co-operatives for agricultural development and improvement of smallholder farmers' livelihoods. The agencies can use the results to initiate interventions relevant for different types of smallholder farmers through co-operatives.Originality/valueThis study highlights the influence of smallholder farmers' financial investments in farming and the extent of commercialisation on co-operative membership. Due to low membership in co-operatives, recognising the heterogeneity of smallholder farmers is the key in agricultural development interventions through co-operative membership.Peer reviewThe peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-03-2022-0165.
They do what they must: caseworkers at the public employment service in Vienna
Authors: Leibetseder Bettina 
Published: September 2022

PurposeConcerning the decision-making of frontline bureaucrats, research has suggested that caseworkers take into account a broader range of legal, organisational, professional and personal aspects. Their decision-making can offset social rights, when it neglects policy goals, but it can support social rights if the decisions consider clients' perspective.Design/methodology/approachBased on a factorial survey experiment with 197 Viennese caseworkers of the employment service, the caseworkers were asked how likely they would be to refer nine different typical clients to the introductory session for the programme “Women into Technical and Craft Professions”, whereby different dimensions were altered to grasp regulations and clients' perspective.FindingsIn the multilevel analysis, the interest of the clients in a technical-educational programme demonstrates the strongest positive effect, which complies with the programme's political intention. Other pertinent criteria may support clients' interests and the organizational performance goals, but neglect clients' position, when they counteract performance goals. Primarily, caseworkers do what they must and follow mandatory and performance criteria.Research limitations/implicationsOn the caseworker's level, further research should aim to reach larger samples. Furthermore, the impact of performance goals on caseworker's decision making has to regard different professional groups beside personnel and labour market experts.Practical implicationsThe findings suggest that a focus on the micro-level is needed to evaluate the impact of social policies. The practitioner's position is crucial to juggling legal goals and client's need.Social implicationsPerformance goals ought to better reflect social rights on a broader scale.Originality/valueThis article provides new evidence on the level of discretion caseworkers execute.
Conflicts between expatriates and host country nationals during the acculturation process
Authors: Dong Longzhu , Ren Hong , He Tingting 
Published: September 2022

PurposeConflict is one of the important aspects of the expatriate-host country nationals (HCNs) dyad. The purpose of this study is to understand how the level of conflict between assigned expatriates and HCNs emerges and evolves during acculturation over time.Design/methodology/approachBuilding on expatriate literature, diversity literature, and acculturation literature, the authors adopted a longitudinal lens and developed a conceptual model to describe the dynamic process of conflict emergence and evolvement between assigned expatriates and HCNs.FindingsThis study offers a dynamic multi-stage conceptual model with the authors' novel propositions to explain how conflicts between assigned expatriates and HCNs emerge and evolve through the acculturation process.Originality/valueThis study provided a theoretical framework demonstrating when and how conflicts between HCNs and expatriates emerge and evolve during acculturation. In doing so, the authors integrate the conflict and diversity literature with the expatriate literature and offer a theoretical foundation to enrich the authors' understanding of the conflict between expatriates and HCNs.
Adoption of social media-based knowledge-sharing behaviour and authentic leadership development: evidence from the educational sector of Pakistan during COVID-19
Authors: Asghar Muhammad Zaheer , Barbera Elena , Rasool Samma Faiz , Seitamaa-Hakkarainen Pirita , Mohelská Hana 
Published: September 2022

Purpose
This research paper aims to explore the influence of social media–based knowledge-sharing intentions (SMKI) on prospective authentic leadership development (ALD) to deal with the future crisis. In the existing literature, to the best of the authors’ knowledge, there is no significant empirical evidence to test the relationship between SMKI and ALD. Thus, this study contributes to the growing literature regarding the role of SMKIs, ALD, social media–based knowledge-sharing behavior (SMKB) and facilitating conditions (FCs). However, in this study, the authors developed a conceptual framework based on technology adoption and leadership theory. It was used to identify preservice educational leaders’ SMKIs and their effect on ALD to deal with an educational crisis during the COVID-19 pandemic. Furthermore, SMKIs are strengthening ALD, directly and indirectly, using SMKB and FCs.

Design/methodology/approach
In this study, the higher education students are considered preservice leaders who were enrolled in educational leadership and management programs. However, this study’s target population and sample are students enrolled in educational leadership and management programs. Therefore, higher education students are considered preservice educational leaders. Therefore, a multilevel questionnaire survey approach was adopted to collect data from preservice educational leaders (n = 451 at Time 1 and n = 398 at Time 2) enrolled in education departments in the selected universities in Pakistan. A total of 398 survey questionnaires were finalized with a return ratio of 89%. The partial least square structural equation modeling with SmartPLS 3.2.8 was used for the data analysis.

Findings
This research found that SMKIs are positively and significantly connected with ALD. This study also confirms that SMKB significantly and positively mediates the relationship between SMKIs and ALD. Therefore, this study concludes that preservice educational leaders were ready to adopt SMKB.

Practical implications
Social media–based knowledge sharing can be helpful to develop authentic leadership among preservice educational leaders during a crisis. Preservice educational leaders as authentic leaders can prove to be an asset in dealing with the COVID-19 pandemic crisis.

Originality/value
This research integrated the technology adoption model and leadership theory to provide empirical evidence of SMKIs’ direct and indirect influence on ALD through social media–based knowledge-sharing actual use behavior by preservice educational leaders during the COVID-19 pandemic. Moreover, the moderated mediating effect of the FCs was also studied in the relationship between SMKIs and actual user behavior as well as ALD.