bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crotamiton derivative JM03 extends lifespan and improves oxidative and hypertonic stress resistance in Caenorhabditis elegans via inhibiting OSM-9
Authors: Bao Keting , Feng Jiali , Liu Wenwen , Mao Zhifan , Bao Lingyuan , Sun Tianyue , Song Zhouzhi , Hu Zelan , Li Jian 
Published: September 2021

AbstractWhile screening our in-house 1,072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic and anti-aging effects, and could further lead to promising application prospects.
OGT controls mammalian cell viability by regulating the proteasome/mTOR/mitochondrial axis
Authors: Li Xiang , Yue Xiaojing , Sepulveda Hugo , Burt Rajan A. , Scott David A. , Carr Steven A. , Myers Samuel A. , Rao Anjana 
Published: September 2021

AbstractO-GlcNAc transferase (OGT) catalyzes the modification of serine and threonine residues on nuclear and cytosolic proteins with O-linked N-acetylglucosamine (GlcNAc). OGT is essential for mammalian cell viability, but the underlying mechanisms are still enigmatic. We employed a genome-wide CRISPR-Cas9 viability screen in mouse embryonic stem cells (mESCs) with inducible Ogt gene deletion and showed that the block in cell viability induced by OGT deficiency stems from mitochondrial dysfunction secondary to mTOR hyperactivation. In normal cells, OGT maintains low mTOR activity and mitochondrial fitness through suppression of proteasome activity; in the absence of OGT, increased proteasome activity results in increased steady-state amino acid levels, which in turn promote mTOR lysosomal translocation and activation, and increased oxidative phosphorylation. mTOR activation in OGT-deficient mESCs was confirmed by an independent phosphoproteomic screen. Our study highlights a novel series of events whereby OGT regulates the proteasome/ mTOR/ mitochondrial axis in a manner that maintains homeostasis of intracellular amino acid levels, mitochondrial fitness and cell viability. A similar mechanism operates in CD8+ T cells, indicating its generality across mammalian cell types. Manipulating OGT activity may have therapeutic potential in diseases in which this signaling pathway is impaired.
Empowering rare variant burden-based gene-trait association studies via optimized computational predictor choice
Authors: Kuang Da , Li Roujia , Wu Yingzhou , Weile Jochen , Hegele Robert A. , Roth Frederick P. 
Published: September 2021

AbstractBackgroundCausal gene/trait relationships can be identified via observation of an excess (or reduced) burden of rare variation in a given gene within humans who have that trait. Although computational predictors can improve the power of such ‘burden’ tests, it is unclear which are optimal for this task.MethodUsing 140 gene-trait combinations with a reported rare-variant burden association, we evaluated the ability of 20 computational predictors to predict human traits. We used the best-performing predictors to increase the power of genome-wide rare variant burden scans based on ∼450K UK Biobank participants.ResultsTwo predictors—VARITY and REVEL—outperformed all others in predicting human traits in the UK Biobank from missense variation. Genome-scale burden scans using the two best-performing predictors identified 1,038 gene-trait associations (FDR < 5%), including 567 (55%) that had not been previously reported. We explore 54 cardiovascular gene-trait associations (including 15 not reported in other burden scans) in greater depth.ConclusionsRigorous selection of computational missense variant effect predictors can improve the power of rare-variant burden scans for human gene-trait associations, yielding many new associations with potential value in informing mechanistic understanding and therapeutic development. The strategy we describe here is generalizable to future computational variant effect predictors, traits and organisms.
Neuromuscular connectomes across development reveal synaptic ordering rules
Authors: Meirovitch Yaron , Kang Kai , Draft Ryan W. , Pavarino Elisa C. , Henao Echeverri Maria Fernanda , Yang Fuming , Turney Stephen G. , Berger Daniel R. , Peleg Adi , Montero-Crespo Marta , Schalek Richard L. , Lu Ju , Livet Jean , Tapia Juan-Carlos , Lichtman Jeff. W. 
Published: September 2021

AbstractIn mammals, the connections between motor neurons and muscle fibers profoundly reorganize in the early postnatal period. To better understand this synaptic rewiring we traced out all the connectivity in muscles at successive ages in the mouse using serial section scanning electron microscopy in a muscle at birth and Brainbow-based and XFP-based fluorescent reconstructions in neonatal and older muscles respectively. Our data indicate that axons prune about 85% of their branches in the first two weeks of postnatal life, and that while much of this pruning leaves neuromuscular junctions with only one remaining axon (a ∼8-fold reduction), it also causes a ∼6-fold reduction in the number of muscle fibers that possess more than one neuromuscular junction. Unexpectedly, the simplification of the wiring diagram was not haphazard but rather was constrained by the tendency for neurons to maintain co-innervation the longest with other neurons based on their proximity in an abstract rank order. This synaptic ordering preference was even significant at birth when connectivity was the most overlapping but became more striking as development proceeded and was even obvious in the few adult muscle fibers that retained more than one axon at different neuromuscular junctions. Analysis of properties of muscle fibers sharing axons at developing ages and changes in the physical distance between neuromuscular junctions that were maintained in young versus older muscles suggests that the rank order of motor neurons is based on their relative similarity in activity patterns. This same ranking governs both the close-proximity synaptic competitions within neuromuscular junctions and the long-distance competitions that remove or maintain synapses millimeters apart meaning that all neuromuscular rewiring is based on the same global activity ordering rule. We think it is likely that this ranking is related to the ultimate recruitment order of motor axon activity as first described by (Henneman, 1957). Thus the emerging structure of neuromuscular circuitry is a product of its function: initial nearly all-to-all connectivity gives rise to a well-organized system of axons, allowing for the orderly recruitment of neurons during a smoothly graded behavior.
Core cysteine residues in the PAN domain are critical for HGF/c-MET signaling
Authors: Pal Debjani , De Kuntal , Shanks Carly M. , Feng Kai , Yates Timothy B. , Morrell-Falvey Jennifer , Davidson Russell B. , Parks Jerry M. , Muchero Wellington 
Published: September 2021

AbstractThe Plasminogen-Apple-Nematode (PAN) domain, with a core of four to six cysteine residues, is found in > 28,000 proteins across 959 genera but its role in protein function is not fully understood. The PAN domain was initially characterized to be present in numerous proteins including hepatocyte growth factor (HGF). Dysregulation of HGF-mediated signaling results in numerous deadly cancers. All biological impacts of HGF in cell proliferation are triggered by binding of HGF to its cell surface receptor, cellular mesenchymal-epidermal transition (c-MET). Here, we show that four PAN domain cysteine residues are essential for HGF/c-MET signaling. Mutating these residues resulted in retardation of perinuclear localization, cellular internalization of HGF and its receptor, c-MET, and c-MET ubiquitination. Our observations indicate that the PAN domain of HGF is required for the c-MET binding and subsequent c-MET autophosphorylation and phosphorylation of its downstream targets, protein kinase B (AKT), extracellular signal-regulated kinase (ERK), and signal transducer and activator of transcription 3 (STAT3). Furthermore, transcriptional activation of HGF/c-MET signaling-related genes including matrix metalloproteinase-9 (MMP9), ETS translocation variant 1, 4, and 5 (ETV1, ETV4, ETV5), and early growth response 1 (EGR1) was impaired and cell proliferation was attenuated. These results suggest that core cysteine residues in the PAN domain are critical for HGF/c-MET interaction, c-MET mediated signal transduction, and cell survival. Thus, targeting the PAN domain of HGF may represent a mechanism for selectively regulating the binding and activation of the c-MET pathway.SignificanceHGF/c-MET signaling induces multifunctional cellular responses. Dysregulation of HGF/c-MET signaling cascade can lead to tumorigenesis by transforming normal cells to tumor cells. This work defines the importance of core cysteine residues in the PAN domain of HGF in downstream activation of HGF/c-MET signaling. To understand the role of cysteines in the PAN domain, PAN mutants of HGF were used to stimulate c-MET signaling in cells and the impact was delineated by determining phosphorylation and transcription of downstream targets. Mutations in core cysteines in the HGF-PAN domain completely blocked downstream phosphorylation and perinuclear accumulation of c-MET. These results suggest an indispensable role for the cysteine-rich PAN domain in HGF/c-MET interaction and could set the stage for future therapies that selectively disrupt the MET signaling cascade with limited off-target effects in tumors overexpressing HGF/c-MET.
Nutritional and quality characteristics of wheat bread fortified with different levels of soaked–dehulled moth bean (Vigna aconitifolia) seeds powder
Authors: Ali Rehab F.M. , Althwab Sami A. , Alfheeaid Hani A. , El-Anany Ayman Mohammed , Alhomaid Raghad M. , Alharbi Hend F. 
Published: September 2021

PurposeSoaked–dehulled moth bean seed (SDMBS) powder was incorporated into wheat flour and the paper aims to investigate its effects on the nutritional and quality properties of composite bread.Design/methodology/approachDifferent ratios of SDMBS powder (0%–12.5%) were mixed into wheat flour to prepare composite bread. Proximate composition, mineral content and functional properties of SDMBS powder and wheat flour were studied. The composite bread samples were assayed for proximate composition, mineral nutrients, amino acid composition, physical characteristics as well as sensorial properties.FindingsProtein and ash contents of SDMBS powder were found to be 2.15 and 5.69 fold higher than wheat flour. Water absorption capacity (WAC), oil absorption capacity (OAC), (FC) and emulsion activity (EA) values of SDMBS powder were also 1.63, 1.78, 4.43 and 1.58 times higher than wheat flour, respectively. The inclusion of different levels of SDMBS powder into wheat flour significantly (p = 0.05) increased the functional properties of composite flours. Bread samples fortified with SDMBS powder exhibited higher values of essential amino acids than the recommendations of World Health Organization/Food and Agriculture Organization/United Nations University (2007). The bread samples containing 10% and 12.5% of SDMBS powder provided 39.23% and 41.15% of the recommended lysine level, respectively. The addition of a higher proportion of SDMBS powder into wheat flour gradually increased the protein and ash contents of the bread samples. Control sample without SDMBS powder (0%) and samples fortified containing 2.5% and 5% of SDMBS powder received the highest scores of overall acceptance, whereas the bread sample with the highest SDMBS powder (12.5%) content received the lowest scores.Research limitations/implicationsThe main findings of the current investigation indicated that the addition of 2.5–5% of SDMBS powder into wheat flour enhanced the nutritional and quality characteristics of wheat bread.Originality/valueSDMBS powder could be incorporated into refined wheat bread to achieve functional bread with significantly higher protein content.
Mission statement effectiveness: investigating managers' sensemaking role
Authors: Toh Seong-Yuen , Tehseen Shehnaz , Mahmoud Ali B. , Cheok Jason , Grigoriou Nicholas , Opute John 
Published: September 2021

PurposeThis study highlights the instrumental role of the mission statement as a tool used by managers to shape value congruence to achieve enhanced employee performance levels.Design/methodology/approachA variance-based structural equation modelling was used to analyse the data obtained from a sample of 123 managers working in private organisations in Malaysia.FindingsThe management sensemaking approach is useful in mission statement research. Managers' involvement in clarifying the mission statement to various firm stakeholders, especially employees, is the strongest predictor of value congruency between employees and the firm, leading to improved levels of employee behavioural performance. Managers can influence value congruency through two processes: (1) guiding and shaping employees' values and (2) adapting the mission statement's contents.Research limitations/implicationsFuture studies can consider the impact of managerial role modelling on employees' value alignment with the firm in longitudinal studies. Other aspects of alignment offer further research opportunities, for example, HR policy alignment and alignment of marketing and operation strategies with the mission statement.Practical implicationsManagers should move beyond treating the mission statement as a management tool. Instead, it is a firm philosophy that reflects managers' words and deeds and exemplifies their philosophical ideals.Originality/valueDespite three decades of research into the relationship between the mission statement and performance, the results have been mixed. Therefore, this study adopts a sensemaking approach to research the mission-performance relationship underpinned by the resource-based view (RBV) theory.
Decoding leadership to leverage employee engagement in virtual teams
Authors: Mutha Prapti , Srivastava Manjari 
Published: September 2021

Purpose
Virtual teams are characterized by short social exchanges and a lack of para-verbal and non-verbal communication. This poses several challenges to virtual leaders. This study aims to decode the role of leadership and understand its impact on engaging geographically dispersed teams. This research offers a comprehensive view of idealized influence and inspirational motivation – the two sub-factors of transformational leadership which defines the charisma of a leader in leveraging engagement of virtual employees. It also studies the impact of effective leadership communication and trust between team members in engaging employees working in virtual teams.

Design/methodology/approach
This research is a mixed method study. Phase I of qualitative study (10 FGD) facilitated phase II of quantitative study. A questionnaire was developed to reflect themes that emerged from qualitative phase. The focus of the qualitative study was to understand the role of leaders viewed by virtual employees in the context of engagement. A cross-sectional data of 300 respondents from eight different industries was gathered using a survey questionnaire. Purposive non-probability sampling technique was used. Data were analyzed using partial least squares structural equation modelling, SmartPLS 3 software.

Findings
Results showed that leaders play a significant role in engaging virtual employees. The transformational leadership behaviour with a purview of idealized influence and inspirational motivation positively engages employees in virtual teams. The findings emphasize that trust between team members impacts engagement, and trust mediates the relationship between leadership communication effectiveness and engagement of virtual employees.

Practical implications
Positive leadership behaviour such as transformational leadership helps create an environment of trust and engagement that is experienced by a team working distantly. Leader plays a critical role to foster an engaging environment that boosts the potential of every employee. Organizations invest a lot of money, time and resources in leadership and communication training. This study could help organizations in training their managers/leaders for adapting their leadership style that suits the virtual work environment. Organizations can also pay attention to the required skill sets of people while hiring and/or promoting leaders who have to lead virtual employees.

Originality/value
The exponential increase in virtual working has necessitated decoding essential leadership skills to engage the virtual workforce. Working virtually is psychologically a different experience and hence requires a separate study. The lack of proximity and face-to-face conversations in virtual teams increases the complexity of leading and thus alters the engagement equation. This paper explores the impact of leaders in enhancing employee engagement and that is presented in a condensed manner.
Sport federations' organizational innovativeness: an empirical comparison of characteristics and attitudes
Authors: Corthouts Joris , Zeimers Géraldine , Helsen Kobe , Demeulemeester Camille , Könecke Thomas , Zintz Thierry , Scheerder Jeroen 
Published: September 2021

PurposeBeing innovative is important for non-profit sport organizations in order to meet the ever-changing and increasing societal needs. Understanding why and to what extent organizational innovativeness differs between non-profit sport organizations is, therefore, important to assess and increase their chances of survival. The purpose of this study is to compare the structural characteristics and attitudes of innovation attributes between three groups of sport federations (SFs).Design/methodology/approachAn online self-assessment survey was sent to all recognized regional Belgian SFs (N = 156). Simultaneously, an observational desk research (i.e. media analysis) was carried out. Results from both data collection methods were combined to develop a composite organizational innovativeness-index, based on which the federations were then clustered in three distinct adopter groups.FindingsComparative statistics show that structural background characteristics generally are poor indicators for adopter categorization. In contrast, the attitudes about compatibility (i.e. the consistency of innovations with existing values) and complexity (i.e. the extent to which innovations are difficult to apprehend) seem the most important distinctive determinants for the different groups of SFs.Originality/valueThe study's contribution is twofold. First, it offers a methodological contribution with the development of an index, which enables the categorization of non-profit sport organizations according to their organizational innovativeness; thus, it provides a critical counter-argument to the importance of organizational structural background characteristics from previous studies. Second, the study's results may support non-profit sport organizations in improving their innovativeness, for instance by improving the perception of compatibility with innovation or by guiding policymakers in creating a more supportive environment for these organizations to do so.
Workplace preparedness for an ageing workforce: a case study
Authors: Egdell Valerie , Maclean Gavin , Raeside Robert , Chen Tao 
Published: September 2021

PurposeFor many nations, their workforces are ageing. The purpose of this paper is to explore the concerns and attitudes of employers to employing older workers and what information they require.Design/methodology/approachA questionnaire survey of workplaces was undertaken in the Fife region of Scotland, which in economic and demographic terms is representative of wider Scotland and other nations in Northern Europe. Descriptive analysis was undertaken to give insight into concerns and actions taken regarding ageing workforces.FindingsMost workplaces perceive more advantages to employing older workers than challenges. Many have adapted training and work practices, but many have not. The majority surveyed believe that existing policies and strategies are sufficient. This points to the need for national and local government and employer associations to become more active to persuade workplaces to better manage future workplaces.Research limitations/implicationsGeneralisability is problematic and the small sample restricted the scope of statistical analysis.Practical implicationsThe authors were unable to judge the severity of how an ageing workforce impacts on workplace performance, as employers found it difficult to conceptualise and identify the impact of ageing from market and economic pressures.Social implicationsResulting from population ageing the workforce of many societies are becoming older, this will impact on workplace relations and the social identity of those over the age of 50 years.Originality/valueLittle research has been undertaken to assess workplaces awareness of, and how to adapt to, an ageing workforce, and research is required to inform and guide management strategy of employers.
What motivates employees to use social media at work? A perspective of self-determination theory
Authors: Wei Shaobo , Chen Xiayu , Liu Chunli 
Published: September 2021

PurposeThe authors develop a conceptual model to examine how three basic psychological needs (i.e. needs for competence, autonomy and relatedness) affect employee social media use (i.e. work- and social-related use). The authors propose that the need for autonomy positively moderates the relationship between need for competence and work-related use, whereas it negatively moderates that between need for relatedness and social-related use.Design/methodology/approachTo test the proposed model, 332 internal and 271 external social media users in the workplace were recruited.FindingsThe results indicate that needs for competence and autonomy and needs for relatedness and autonomy positively affect the work- and social-related use, respectively, of internal and external social media. Need for autonomy positively moderates the relationship between need for competence and work-related use of internal social media, and it negatively moderates that between need for relatedness and the social-related use of internal social media. Need for autonomy has no moderating effect on the relationship between need for competence and work-related use, whereas it negatively moderates the relationship between need for relatedness and the social-related use of external social media.Originality/valueFirst, the authors’ findings offer significant empirical support for the different social media uses, namely work and social related. Second, this study highlights the importance of psychological needs of employees in determining the form of social media use. Third, this study empirically demonstrates the differences in psychological needs and social media use between two different social media contexts.