bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solution structure, dynamics and tetrahedral assembly of Anti-TRAP, a homo-trimeric triskelion-shaped regulator of tryptophan biosynthesis inBacillus subtilis
Authors: McElroy Craig , Ihms Elihu , Yadav Deepak Kumar , Holmquist Melody , Wadwha Vibhuti , Wysocki Vicki , Gollnick Paul , Foster Mark 
Published: July 2023

AbstractCellular production of tryptophan is metabolically expensive and tightly regulated. The smallBacillus subtiliszinc binding Anti-TRAP protein (AT), which is the product of theyczA/rtpAgene, is upregulated in response to accumulating levels of uncharged tRNATrpthrough a T-box antitermination mechanism. AT binds to the undecameric ring-shaped protein TRAP (trpRNA Binding Attenuation Protein), thereby preventing it from binding to thetrpleader RNA. This reverses the inhibitory effect of TRAP on transcription and translation of thetrpoperon. AT principally adopts two symmetric oligomeric states, a trimer (AT3) featuring a three-helix bundle, or a dodecamer (AT12) comprising a tetrahedral assembly of trimers, whereas only the trimeric form has been shown to bind and inhibit TRAP. We demonstrate the utility of native mass spectrometry (nMS) and small-angle x-ray scattering (SAXS), together with analytical ultracentrifugation (AUC) for monitoring the pH and concentration-dependent equilibrium between the trimeric and dodecameric structural forms of AT. In addition, we report the use of solution nuclear magnetic resonance (NMR) spectroscopy to determine the solution structure of AT3, while heteronuclear15N relaxation measurements on both oligomeric forms of AT provide insights into the dynamic properties of binding-active AT3and binding-inactive AT12, with implications for TRAP inhibition.
Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation
Authors: Mitchell Wayne , Goeminne Ludger J.E. , Tyshkovskiy Alexander , Zhang Sirui , Chen Julie Y. , Paulo Joao A. , Pierce Kerry A. , Choy Angelina H. , Clish Clary B. , Gygi Steven P. , Gladyshev Vadim N. 
Published: July 2023

ABSTRACTPartial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset of many diseases of aging. However, the delivery of transgenes and potential risk of teratoma formation present challenges forin vivoapplications. Recent advances include the use of cocktails of compounds to reprogram somatic cells, but the characteristics and mechanisms of partial cellular reprogramming by chemicals remain unclear. Here, we report a multi-omics characterization of partial chemical reprogramming in fibroblasts from young and aged mice. We measured the effects of partial chemical reprogramming on the epigenome, transcriptome, proteome, phosphoproteome, and metabolome. At the transcriptome, proteome, and phosphoproteome levels, we saw widescale changes induced by this treatment, with the most notable signature being an upregulation of mitochondrial oxidative phosphorylation. Furthermore, at the metabolome level, we observed a reduction in the accumulation of aging-related metabolites. Using both transcriptomic and epigenetic clock-based analyses, we show that partial chemical reprogramming reduces the biological age of mouse fibroblasts. We demonstrate that these changes have functional impacts, as evidenced by changes in cellular respiration and mitochondrial membrane potential. Taken together, these results illuminate the potential for chemical reprogramming reagents to rejuvenate aged biological systems and warrant further investigation into adapting these approaches forin vivoage reversal.
FruitFire: a luciferase based on a fruit fly metabolic enzyme
Authors: Adams Spencer T. , Zephyr Jacqueto , Bohn Markus F. , Schiffer Celia A. , Miller Stephen C. 
Published: July 2023

AbstractFirefly luciferase is homologous to fatty acyl-CoA synthetases from insects that are not bioluminescent. Here, we determined the crystal structure of the fruit fly fatty acyl-CoA synthetase CG6178 to 2.5 Å. Based on this structure, we mutated a steric protrusion in the active site to create the artificial luciferase FruitFire, which prefers the synthetic luciferin CycLuc2 to D-luciferin by >1000-fold. FruitFire enabled in vivo bioluminescence imaging in the brains of mice using the pro-luciferin CycLuc2-amide. The conversion of a fruit fly enzyme into a luciferase capable of in vivo imaging underscores the potential for bioluminescence with a range of adenylating enzymes from nonluminescent organisms, and the possibilities for application-focused design of enzyme-substrate pairs.
Epiboly in zebrafish requires the coordinated activity of NADPH oxidases and dynamin
Authors: Mendez-Cruz Francisco J. , Ramírez-Corona Arlen , Reza-Medina Brenda , Mendieta-Serrano Mario A. , Schnabel Denhi , Lomelí Hilda , Salas-Vidal Enrique 
Published: July 2023

Withdrawal statementThe authors have withdrawn their manuscript owing to significant errors in figures 1, 3, 6, and supplementary figure 3. Also, because some of the results were incorrectly reported. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Co-translational ribosome pairing enables native assembly of misfolding-prone subunits
Authors: Wruck Florian , Schmitt Jaro , Fenzl Kai , Bertolini Matilde , Katranidis Alexandros , Bukau Bernd , Kramer Günter , Tans Sander 
Published: July 2023

AbstractProtein complexes are pivotal to most cellular processes. Emerging evidence indicates that pairs of ribosomes ubiquitously drive the synchronized synthesis and assembly of two protein subunits into homodimeric complexes1-5. These observations suggest protein folding mechanisms of general importance enabled by contacts between nascent chains6,7– which have thus far rather been considered detrimental8,9. However, owing to their dynamic and heterogeneous nature, the folding of interacting nascent chains remains unexplored. Here, we show that co-translational ribosome pairing allows their nascent chains to ‘chaperone each other’, thus enabling the formation of coiled-coil homodimers from subunits that misfold individually. We developed an integrated single-molecule fluorescence and force spectroscopy approach to probe the folding and assembly of two nascent chains extending from nearby ribosomes, using the intermediate filament lamin as a model system. Ribosome proximity in early translation stages was found to be critical: when interactions between nascent chains are inhibited or delayed, they become trapped in stable misfolded states that are no longer assembly competent. Conversely, early interactions allow the two nascent chains to nucleate native-like quaternary structures that grow in size and stability as translation advances. We conjecture that protein folding mechanisms enabled by ribosome cooperation are more broadly relevant to intermediate filaments and other protein classes.
Distinct functional constraints driving conservation of the cofilin N-terminal regulatory tail
Authors: Sexton Joel A. , Potchernikov Tony , Bibeau Jeffrey P. , Casanova-Sepúlveda Gabriela , Cao Wenxiang , Lou Hua Jane , Boggon Titus J. , De La Cruz Enrique M. , Turk Benjamin E. 
Published: July 2023

SummaryCofilin family proteins have essential roles in remodeling the cytoskeleton through filamentous actin depolymerization and severing. The short unstructured N-terminal region of cofilin is critical for actin binding and harbors the major site of inhibitory phosphorylation. Atypically for a disordered sequence, the N-terminal region is highly conserved, but the aspects of cofilin functionality driving this conservation are not clear. Here, we screened a library of 16,000 human cofilin N-terminal sequence variants for their capacity to support growth inS. cerevisiaein the presence or absence of the upstream regulator LIM kinase. Results from the screen and subsequent biochemical analysis of individual variants revealed distinct sequence requirements for actin binding and regulation by LIM kinase. While the presence of a serine, rather than threonine, phosphoacceptor residue was essential for phosphorylation by LIM kinase, the native cofilin N-terminus was otherwise a suboptimal LIM kinase substrate. This circumstance was not due to sequence requirements for actin binding and severing, but rather appeared primarily to maintain the capacity for phosphorylation to inactivate cofilin. Overall, the individual sequence requirements for cofilin function and regulation were remarkably loose when examined separately, but collectively restricted the N-terminus to sequences found in natural cofilins. Our results illustrate how a regulatory phosphorylation site can balance potentially competing sequence requirements for function and regulation.
Chemogenetic profiling of ubiquitin-like modifier pathways identifies NFATC2IP as a mediator of SUMO-dependent genome integrity
Authors: Cho Tiffany , Zhao Yichao , Olivieri Michele , Hoeg Lisa , Setiaputra Dheva , Durocher Daniel 
Published: July 2023

AbstractThe post-translational modification of proteins by ubiquitin and ubiquitin-like polypeptides controls multiple cellular processes including the abundance of a large fraction of the proteome. We applied genome-scale CRISPR/Cas9 screens to elucidate the genetic architecture of the response to inhibition of ubiquitin, NEDD8 and SUMO conjugation pathways as well as inhibition of the p97/VCP segregase. This effort identified 395 genes whose disruption alters the fitness of human cells when faced with perturbations in these pathways. We validated that the TMED2 and TMED10 proteins, which are localized to the secretory pathway, promote resistance to p97/VCP inhibition and also characterized NFATC2IP, an evolutionarily conserved protein harboring SUMO-like domains as a major player in promoting genomic integrity when SUMOylation is inhibited. We propose that NFATC2IP acts in interphase cells to promote the SUMO-dependent E3 ligase activity of the SMC5/SMC6 complex, which is critical for SUMO-dependent genome integrity.
Differential susceptibility of male and female germ cells to glucocorticoid-mediated signaling
Authors: Cincotta Steven A. , Richardson Nainoa , Foecke Mariko H. , Laird Diana J. 
Published: July 2023

AbstractWhile physiologic stress has long been known to impair mammalian reproductive capacity through hormonal dysregulation, mounting evidence now suggests that stress experienced prior to or during gestation may also negatively impact the health of future offspring. Rodent models of gestational physiologic stress can induce neurologic and behavioral changes that persist for up to three generations, suggesting that stress signals can induce lasting epigenetic changes in the germline. Treatment with glucocorticoid stress hormones is sufficient to recapitulate the transgenerational changes seen in physiologic stress models. These hormones are known to bind and activate the glucocorticoid receptor (GR), a ligand-inducible transcription factor, thus implicating GR-mediated signaling as a potential contributor to the transgenerational inheritance of stress-induced phenotypes. Here we demonstrate dynamic spatiotemporal regulation of GR expression in the mouse germline, showing expression in the fetal oocyte as well as the perinatal and adult spermatogonia. Functionally, we find that fetal oocytes are intrinsically buffered against changes in GR signaling, as neither genetic deletion of GR nor GR agonism with dexamethasone altered the transcriptional landscape or the progression of fetal oocytes through meiosis. In contrast, our studies revealed that the male germline is susceptible to glucocorticoid-mediated signaling, specifically by regulating RNA splicing within the spermatogonia, although this does not abrogate fertility. Together, our work suggests a sexually dimorphic function for GR in the germline, and represents an important step towards understanding the mechanisms by which stress can modulate the transmission of genetic information through the germline.
Performance predictions for sustainability governance of firms: implications to select Indian firms
Authors: Rajesh R. 
Published: July 2023

PurposeThe author aims to study and predict the sustainability governance performances of firms using an advanced grey prediction model. The case implication of the prediction model is also studied considering select firms in the Indian context.Design/methodology/approachThe author has proposed an advanced grey prediction model, the first-entry grey prediction model (FGM (1, 1)) for forecasting the sustainability governance performances of firms. The proposed model is tested using the periodic data of sustainability governance performances of 10 Indian firms.FindingsThe author observes that the majority of firms (6 out of 10) show dipping performances for sustainability governance for the future predicted period. This throws insights into the direction of improving good governance practices for Indian firms.Practical implicationsThe idea and motivation for sustainability-focussed governance need a bi-directional focus from the side of managers that act as the agents and from the side of shareholders that act as the principals, as seen from an agency theory perspective for sustainability governance.Social implicationsSustainability governance culture can be inculcated to a firm at the strategic level by having a bi-directional focus from managers and shareholders, so as to enhance the social and environmental sustainability performances.Originality/valueThe governance performance evaluations for firms particularly in developing countries were not dated back more than a decade or two. Hence, the author implements a prediction model that can be best suited, when there are small periodic data sets available for prediction.
The impact of social media marketing on new venture performance
Authors: Venciute Dominyka , Auruskeviciene Vilte , Reardon James 
Published: July 2023

PurposeThe purpose of this paper is to examine the impact of social media marketing on new venture performance utilizing Structure-Conduct-Performance (SCP) theory.Design/methodology/approachA survey approach was employed, and questionnaires were sent out to the representatives of new ventures established in the previous six years at the time of data collection. Measures were adapted from SCP theory and the measurement model examined. A total of 248 responses were analyzed using structural equation modelling (LISREL 11).FindingsThe results indicate that social media marketing capabilities have a positive impact on the marketing performance of new ventures through a mediating effect of social media marketing performance. Thus, social media marketing performance affects new venture performance through marketing performance.Research limitations/implicationsThis research supports the vitality of social media in the lives of new firms and the importance of social media when executing marketing activities. The perceptive measurement of social media marketing capabilities on the firm level can be useful for new ventures to evaluate their competencies related to social media, and thus help firms improve those capabilities over time.Originality/valueThis research contributes to the existing knowledge on linkages between social media marketing capabilities and new venture performance acknowledging the role of a turbulent market environment. Therefore, the recognition of industry structure articulated by a turbulent market environment, social media marketing capabilities and social media support for competitive marketing strategy answers the question of how social media marketing capabilities drive competitive marketing strategy and subsequently influence performance.
The mentoring needs of recently appointed female middle leaders: an Australian case study
Authors: Blake Caroline , Fielding Mark 
Published: July 2023

PurposeThere is a significant volume of literature relating to the mentoring needs of new principals and vice/deputy principals, but little is known about the mentoring needs of recently appointed middle leaders in an educational setting. This study explored the mentoring needs of five female middle leaders at a K–12 case study school of 550 students in Perth, Australia.Design/methodology/approachEach participant had three mentoring sessions, followed by a semi-structured interview using open-ended questions to provide data on the participants' mentoring needs. The research was framed within an interpretive phenomenology paradigm that focussed on the participants' perceived experiences and how they then interpreted these experiences. One of the researchers was active in this research, acting as the mentor (Neubauer et al., 2019; Smith and Osborn, 2021).FindingsThe findings of this study revealed the importance of the mentor being a “critical friend”. In addition, the participants referred to leadership identity, leadership from the middle, managing relationships and gender as other important mentoring needs.Originality/valueThis empirical study contributes original findings on the mentoring needs of a previously neglected group of educational leaders who provide an essential bridge between classroom practitioners and senior leadership in Australian schools. This study is unique because it links these mentoring needs to the practice architectures, factors at the case study school that either constrained or enabled middle leading (Kemmis et al., 2014).
Increasing mobile health application usage among Generation Z members: evidence from the UTAUT model
Authors: Aydin Gokhan 
Published: July 2023

PurposeThe acceptance of mobile health (m-health) applications, especially those of a preventive nature, by individuals, is not well understood. Despite the benefits offered by m-health applications in improving and sustaining health and well-being through various avenues, widespread adoption is yet to be seen. Within this context, this study aims to reveal the enabling factors and barriers that influence the use of m-health applications among Generation Z (Gen-Z).Design/methodology/approachThe Unified Theory of Acceptance and Use of Technology (UTAUT) was extended with e-health literacy, trust and enjoyment constructs. Data from a survey study on 312 Gen-Z members were analysed via structural equation modelling, shedding light on the reasons why new generations adopt m-health apps.FindingsThe findings indicate that social influence and enjoyment are the most significant factors influencing the use of m-health apps. The significant impact of performance and effort expectancy on intentions was also confirmed by the results. Moreover, privacy risk was identified as a barrier to adoption. The results also indicated that the strong influence of trust on privacy risk can be used to offset those privacy concerns.Practical implicationsThe findings highlight that hedonic motivation, which is commonly overlooked in health settings, plays an important role in m-health app use. Thus, promoting mobile app features that provide enjoyment will be influential in attracting the younger generation.Originality/valueThe context of the study differs from the norm and focuses on a regional health tourism hub, Turkey, situated at the crossroads of Europe and Asia. UTAUT model is modified with relevant constructs, namely, enjoyment, e-health literacy and privacy risk, to better fit the m-health context.
A convolutional neural network to identify the change point of a multistage process profile with cascade property
Authors: Atashgar Karim , Boush Mahnaz 
Published: July 2023

PurposeWhen a process experiences an out-of-control condition, identification of the change point is capable of leading practitioners to an effective root cause analysis. The change point addresses the time when a special cause(s) manifests itself into the process. In the statistical process monitoring when the chart signals an out-of-control condition, the change point analysis is an important step for the root cause analysis of the process. This paper attempts to propose a model approaching the artificial neural network to identify the change point of a multistage process with cascade property in the case that the process is modeled properly by a simple linear profile.Design/methodology/approachIn practice, many processes can be modeled by a functional relationship rather than a single random variable or a random vector. This approach of modeling is referred to as the profile in the statistical process control literature. In this paper, two models based on multilayer perceptron (MLP) and convolutional neural network (CNN) approaches are proposed for identifying the change point of the profile of a multistage process.FindingsThe capability of the proposed models are evaluated and compared using several numerical scenarios. The numerical analysis of the proposed neural networks indicates that the two proposed models are capable of identifying the change point in different scenarios effectively. The comparative sensitivity analysis shows that the capability of the proposed convolutional network is superior compared to MLP network.Originality/valueTo the best of the authors' knowledge, this is the first time that: (1) A model is proposed to identify the change point of the profile of a multistage process. (2) A convolutional neural network is modeled for identifying the change point of an out-of-control condition.
Management's internal governance policies on flexible work practices and the mediating lens of work life enrichment – Outcome for employee work engagement and organizational attractiveness
Authors: Khan Asif , Khan Ashfaq , Shah Tazeem Ali , Nisar Khattak Mohammad , Abukhait Rawan 
Published: July 2023

PurposeUsing Pakistan's public sector higher education institutions as the study site, this study aims to empirically substantiate, under the theoretical underpinnings of job enrichment theory (Hackman and Oldham, 1976) and Maslow's (1943) theory of the hierarchy of needs, the impact of flexible work practices (FWPs), on employee work engagement and organizational attractiveness, with the mediating lens of work life enrichment.Design/methodology/approachField data were collected at five higher education institutions located in the Islamabad Capital Territory (ICT) of Pakistan, using the convenience sampling technique and analyzed under the quantitative research paradigm.FindingsThis study substantiates with an empirical evidence that flexible work practices (FWPs) have a significant positive impact on both employee work engagement and organizational attractiveness. Markedly, the study findings reveal that the said impact is significantly stronger than that of sabbaticals. Furthermore, the study reveals that the positive relationship is mediated by work life enrichment, signaling its significance in understanding FWP's such impact on employee work engagement and organizational attractiveness.Practical implicationsThe study findings provide significant implications for academia, practitioners, and policymakers, in evidence-based recommendations for higher education institutions to design and implement FWPs that are effective in enhancing employee work engagement and organizational attractiveness, and, in turn, leading to improved organizational performance.Originality/valueThis research study provides a novel contribution to the existing literature by exploring the combined impact of flexible work practices on employee work engagement and organizational attractiveness in the peculiar context of Pakistan's public sector higher education institutions. Additionally, the study's focus on the mediating role of work life enrichment further adds to its novelty.