bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal Structure of Caryolan-1-ol Synthase, a Sesquiterpene Synthase Catalyzing an Initial Anti-Markovnikov Cyclization Reaction
Authors: Kumar Ramasamy P. , Matos Jason O. , Black Brandon Y. , Ellenburg William H. , Chen Jiahua , Patterson MacKenzie , Gehtman Jacob A. , Theobald Douglas L. , Krauss Isaac J. , Oprian Daniel D. 
Published: May 2024

ABSTRACTIn a continuing effort to understand reaction mechanisms of terpene synthases catalyzing initial anti-Markovnikov cyclization reactions, we solved the X-ray crystal structure of (+)-caryolan-1-ol synthase (CS) fromStreptomyces griseus, with and without an inactive analog of the FPP substrate, 2-fluorofarnesyl diphosphate (2FFPP), bound in the active site of the enzyme. The CS-2FFPP complex was solved to 2.65 Å resolution and showed the ligand in a linear, elongated orientation, incapable of undergoing the initial cyclization event to form a bond between carbons C1 and C11. Intriguingly, the apo CS structure (2.2 Å) also had electron density in the active site, in this case density that was well fit with a curled-up tetraethylene glycol molecule presumably recruited from the crystallization medium. The density was also well fit by a molecule of farnesene suggesting that the structure may mimic an intermediate along the reaction coordinate. The curled-up conformation of tetraethylene glycol was accompanied by dramatic rotamer shifts among active-site residues. Most notably, W56 was observed to undergo a 90° rotation between the 2FFPP complex and apo-enzyme structures, suggesting that it contributes to steric interactions that help curl the tetraethylene glycol molecule in the active site, and by extension perhaps also a derivative of the FPP substrate in the normal course of the cyclization reaction. In support of this proposal, the CS W56L variant lost the ability to cyclize the FPP substrate and produced only the linear terpene products farnesol and α- and β-farnesene.
Loss of Intracellular Fibroblast Growth Factor 14 (iFGF14)Increasesthe Excitability of Mature Hippocampal and Cortical Pyramidal Neurons
Authors: Ransdell Joseph L. , Carrasquillo Yarimar , Bosch Marie K. , Mellor Rebecca L. , Ornitz David M. , Nerbonne Jeanne M. 
Published: May 2024

ABSTRACTMutations inFGF14, which encodes intracellular fibroblast growth factor 14 (iFGF14), have been linked to spinocerebellar ataxia type 27 (SCA27), a multisystem disorder associated with progressive deficits in motor coordination and cognitive function. Mice (Fgf14-/-) lacking iFGF14 display similar phenotypes, and we have previously shown that the deficits in motor coordination reflectreducedexcitability of cerebellar Purkinje neurons, owing to the loss of iFGF14-mediated regulation of the voltage-dependence of inactivation of the fast transient component of the voltage-gated Na+(Nav) current, INaT. Here, we present the results of experiments designed to test the hypothesis that loss of iFGF14 also attenuates the intrinsic excitability of mature hippocampal and cortical pyramidal neurons. Current-clamp recordings from adult mouse hippocampal CA1 pyramidal neurons in acutein vitroslices, however, revealed that repetitive firing rates werehigherinFgf14-/-, than in wild type (WT), cells. In addition, the waveforms of individual action potentials were altered inFgf14-/-hippocampal CA1 pyramidal neurons, and the loss of iFGF14 reduced the time delay between the initiation of axonal and somal action potentials. Voltage-clamp recordings revealed that the loss of iFGF14 altered the voltage-dependence of activation, but not inactivation, of INaTin CA1 pyramidal neurons. Similar effects of the loss of iFGF14 on firing properties were evident in current-clamp recordings from layer 5 visual cortical pyramidal neurons. Additional experiments demonstrated that the loss of iFGF14does notalter the distribution of anti-Nav1.6 or anti-ankyrin G immunofluorescence labeling intensity along the axon initial segments (AIS) of mature hippocampal CA1 or layer 5 visual cortical pyramidal neuronsin situ. Taken together, the results demonstrate that, in contrast with results reported for neonatal (rat) hippocampal pyramidal neurons in dissociated cell culture, the loss of iFGF14 doesnotdisrupt AIS architecture or Nav1.6 localization/distribution along the AIS of mature hippocampal (or cortical) pyramidal neuronsin situ.
Discovery of CRBN-dependent WEE1 Molecular Glue Degraders from a Multicomponent Combinatorial Library
Authors: Razumkov Hlib , Jiang Zixuan , Baek Kheewoong , You Inchul , Geng Qixiang , Donovan Katherine A. , Tang Michelle T. , Metivier Rebecca J. , Mageed Nada , Seo Pooreum , Li Zhengnian , Byun Woong Sub , Hinshaw Stephen M. , Sarott Roman C. , Fischer Eric S. , Gray Nathanael S. 
Published: May 2024

AbstractSmall molecules promoting protein-protein interactions produce a range of therapeutic outcomes. Molecular glue degraders exemplify this concept due to their compact drug-like structures and ability to engage targets without reliance on existing cognate ligands. While Cereblon molecular glue degraders containing glutarimide scaffolds have been approved for treatment of multiple myeloma and acute myeloid leukemia, the design of new therapeutically relevant monovalent degraders remains challenging. We report here an approach to glutarimide-containing molecular glue synthesis using multicomponent reactions as a central modular core-forming step. Screening the resulting library identified HRZ-01 derivatives that target casein kinase 1 alpha (CK1α) and Wee-like protein kinase (WEE1). Further medicinal chemistry efforts led to identification of selective monovalent WEE1 degraders that provide a potential starting point for the eventual development of a selective chemical degrader probe. The structure of the hit WEE1 degrader complex with CRBN-DDB1 and WEE1 provides a model of the protein-protein interface and a rationale for the observed kinase selectivity. Our findings suggest that modular synthetic routes combined with in-depth structural characterization give access to selective molecular glue degraders and expansion of the CRBN-degradable proteome.
Evolutionary conservedcis-transregulation machinery for diterpenoid phytoalexin production in Poaceae
Authors: Liu Youming , Tomiyama Shiho , Motegi Ikuya , Yamamoto Naoki , Zheng Aiping , Mori Masaki , Kawahara Maki , Tsujii Yoshimasa , Miyamoto Koji , Furumi Hiroyasu , Sato Yutaka , Nojiri Hideaki , Okada Kazunori 
Published: May 2024

SummaryMomilactones and phytocassanes are diterpenoid phytoalexins involved in plant chemical defense. These metabolites, along with biosynthetic gene clusters (BGCs), are conserved in wild rice. However, the mechanisms by which phytoalexins are regulated in wild rice are unclear. Thus, we aimed to investigate the regulatory mechanisms for biosynthetic genes within the BGCs of diterpenoid phytoalexins.We conducted a transcriptome analysis of five wild rice species,Oryza rufipogon,Oryza punctata,Oryza officinalis,Oryza brachyantha, andLeersia perrieri, after CuCl2treatment.Among the CuCl2-responsive transcription factors, diterpenoid phytoalexin factor (DPF), which regulates phytoalexin production in cultivated rice (Oryza sativa), was broadly conserved in wild rice and showed phytoalexin-inducing activity when introduced into cultivated rice. Highly conserved genomic regions containing N-boxes (5′-CACGAG-3′), the potential binding motif of DPF, were found. CRISPR/Cas9 genome editing to remove these regions showed that biosynthetic gene expression and phytoalexin production were significantly attenuated after CuCl2treatment in the leaves of the edited plants. Thus, thecis-transfactor combination of DPF and N-boxes is a key determinant of regulation.DPF has evolved as a strongcis-transregulatory system for diterpenoid phytoalexin production, with N-boxes generated within the cluster region during the evolution from wild rice to cultivated rice.
Pay dissatisfaction and withdrawal behaviour of employees in the civil service: does personal income tax regime matter?
Authors: Court Timinepere Ogele , Appiah Alaowei Kingsley 
Published: May 2024

PurposeThe aim of the study is to explore the links between multiple personal income tax regimes, pay dissatisfaction, employee lateness and absenteeism. Accordingly, this paper examines the relationships between income tax policies, pay dissatisfaction and the work withdrawal behaviours of employees in the public service.Design/methodology/approachThe study adopted a quantitative design, and data were collected through a structured questionnaire from a sample of 252 respondents from the Bayelsa State Civil Service in Nigeria. Data were analysed by applying multivariate regression and structural equation modelling through the use of Stata software version 12 and SmartPLS version 4.FindingsThe results demonstrated that there was a positive relationship between personal income tax regimes and pay dissatisfaction; there was a positive relationship between pay dissatisfaction and work withdrawal behaviour of employee tardiness and absenteeism and pay dissatisfaction mediated the relationships between personal income tax regimes and work withdrawal behaviours of public sector employees.Originality/valueThe study appears to be the first to explore the nexus between personal income tax regimes and pay dissatisfaction and withdrawal behaviours of employee tardiness and absenteeism as well as the mediating role of pay dissatisfaction in public service organisations.
Modification of HFACS model for path identification of causal factors of collapse accidents in the construction industry
Authors: Qi Haonan , Zhou Zhipeng , Irizarry Javier , Deng Xiaopeng , Yang Yifan , Li Nan , Zhou Jianliang 
Published: May 2024

PurposeThis study aims to modify the human factors analysis and classification system (HFACS) to make it suitable for collapse accident analysis in construction. Based upon the modified HFACS, distribution patterns of causal factors across multiple levels were discerned among causal factors of various stakeholders at construction sites. It explored the correlations between two causal factors from different levels and further determined causation paths from two perspectives of level and stakeholder.Design/methodology/approachThe main research framework consisted of data collection, coding and analysis. Collapse accident reports were collected with adequate causation information. The modified HFACS was utilized for coding causal factors across all five levels in each case. A hybrid approach with two perspectives of level and stakeholder was proposed for frequency analysis, correlation analysis and path identification between causal factors.FindingsEight causal factors from external organizations at the fifth level were added to the original HFACS. Level-based correlation analyses and path identification provided safety managers with a holistic view of inter-connected causal factors across five levels. Stakeholder-based correlation analyses between causal factors from the fifth level and its non-adjacent levels were implemented based on client, government and third parties. These identified paths were useful for different stakeholders to develop specific safety plans for avoiding construction collapse accidents.Originality/valueThis paper fulfils an identified need to modify and utilize the HFACS model for correlation analysis and path identification of causal factors resulting in collapse accidents, which can provide opportunities for tailoring preventive and protective measures at construction sites.
To internalize or not? Addressing key differences between Turkish migrant and native workers in construction employment
Authors: Yılmaz İsmail Cengiz , Tekin Hamdi 
Published: May 2024

PurposeMigration is on the rise due to globalization and human mobility. This has led to increased impacts that have affected many industries, including the construction industry. A large number of migrants are employed in the construction sector, and employers are challenged to make sure all employees are properly integrated to meet the demands needed for construction projects. This article addresses key differences between migrant and native workers to help hiring departments in the construction industry analyse workers' attitudes based on cultural and motivational factors to have the workforce they need to succeed.Design/methodology/approachThe research used both quantitative and qualitative surveys. A two-part questionnaire, designed through a comprehensive literature review, was carried out to identify key differences between native and migrant workers. The data were obtained and then analysed using different statistical approaches, including factor analysis protocol, factor structure model, reliability analysis, relative importance index and nonparametric test analysis. A semi-structured interview was then conducted to discuss all the findings.FindingsThe study indicated that migrant workers, compared to natives, tend to give more importance to their working environment, particularly accommodation, work safety and relations with teammates. Also, migrants typically take a socialistic approach instead of an individual approach while at work and reveal an extensive range of behaviours based on a sense of belonging. It might be more important for migrants to have a place in society, to have a settled life and to be integrated into an established order than to improve their rights and benefits. On the other hand, the study argued that native workers tend to prioritize their benefits at work, such as regular payments for overtime and insurance premiums. Their behaviours might carry a more neutral and individual attitude as well as specific cultural traces.Research limitations/implicationsThe study is limited to a sample of participants in the Turkish construction sector. Further research based on more cultural models and motivational factors with a larger group of respondents from different countries could offer better results. The results of the study might not apply to a broad context due to many other factors that affect worker behaviours, such as geography, cultural structures and working conditions. Despite these drawbacks, the present paper may help employers and other stakeholders understand the best way to incorporate migrants into the construction industry.Originality/valueThis research is very important for the construction industry in various countries that are currently employing thousands of migrants. Being able to address the key differences between migrants and native workers based on cultural and motivational factors might help with engagement and create a level of harmony in the field for greater productivity.
Therapeutic gardening in English prisons post-pandemic: implications for health and wellbeing
Authors: Farrier Alan , Baybutt Michelle 
Published: May 2024

PurposeGreener on the Outside for Prisons (GOOP) is a therapeutic horticulture programme targeting the high levels of complex health and social care needs in prisons in England. The COVID-19 pandemic and resulting lockdowns led to unprecedented disruption in prisons in England. This paper examines the experiences of prisoners both during and post-lockdowns in four prisons, to understand the effects of participation in GOOP on health and wellbeing after the disruption of restrictions, and identify implications for developing this programme further.Design/methodology/approachThe paper is based on original qualitative data gathered from in-depth narrative-based interviews and focus groups with prisoners and staff in four English prisons. Audio data was transcribed and subject to a thematic analysis, drawing from a realist-informed lens.FindingsThematic analysis revealed five key themes: reimagining the GOOP context; increasing empathy between participants; building sense of coherence; reconnecting with nature and a joined-up connection with provider services. The main arguments centre on horticulture in prisons remaining under-utilised as a means of promoting good health and wellbeing, although there is enthusiasm from staff to provide green spaces for the most vulnerable prisoners and develop a range of mechanisms to connect people in prison with nature.Originality/valueThis paper focuses on new knowledge arising from an unprecedented situation in English prisons, from key stakeholders on the frontline of garden activities. Accounts demonstrate the extent of the health and wellbeing benefits of participation in such activities in this challenging environment, which has implications for practice for prisons more widely.
Empowering children for better health with child-to-child approach: a systematic literature review
Authors: Mittal Palka , Kalra Sheetal , Dadhich Abhishek , Ajmera Puneeta 
Published: May 2024

PurposeChild-to-Child (C-to-C) approach is an evidence-based approach that ensures the child’s participation in bringing about positive changes in healthcare. By systematically investigating the literature, the study aimed to evaluate the effectiveness of the approach and recognize associated themes, methodologies and outcomes.Design/methodology/approachAn extensive search on PubMed, ProQuest, Cochrane and Dimensions AI databases was performed for original research articles on C-to-C intervention, with no time and geographical restrictions. Following PRISMA and PICO, the Joanna Briggs Institute (JBI) critical appraisal tool assessed the studies. A data tabulation technique was used to summarize these studies.FindingsThe approach shows promising results in enhancing children’s understanding of health issues and their participation in community health promotion. This, in turn, encourages the adoption of better healthcare practices and shows improved health outcomes.Research limitations/implicationsFurther research is required to understand the long-term impact of the approach on populations from diverse socioeconomic statuses in different study settings.Practical implicationsThe findings will be helpful for practitioners, educators, policymakers and other stakeholders in creating more successful and effective C-to-C intervention programs to make informed decisions, achieve sustainable behavior change and improve health.Originality/valueThe originality of this review paper is evident in its unique focus on the C-to-C approach, which empowers children not only as recipients of health education but also as active contributors to promoting health. Further, the present research also explores the intricacies of how children learn from each other, offering new insights into effective educational practices.
Beyond the hard and soft skills paradigm: an Australian architecture industry perspective on employability and the university/practice divide
Authors: Smith Sebastian , Dupre Karine , Crough Julie 
Published: May 2024

PurposeThis study explores practitioners’ perspectives on the perceived gap between university and practice beyond the hard and soft skill paradigm. Utilising Tomlinson’s graduate capital model of employability (2017), we explored human, social, cultural, and psychological capitals to enrich the understanding of this issue and employability. It provided a new perspective, useful for implementing curriculum renewal.Design/methodology/approachThis study utilised a two-stage mixed methods design. Using Tomlinson’s (2017) Graduate capital model as a framework, the first stage involved distributing an online survey to qualified architects in hiring positions practising in Australia. This served as the foundation for generating qualitative and quantitative data. The second stage involved a two-hour practitioner workshop where the survey results were discussed and expanded upon.FindingsOur results found that the practitioner’s perspective on the perceived skills gap is more complex than the hard/soft skill paradigm commonly discussed. Practitioners expressed a need for students/graduates to possess identity and cultural capital to contextualise industry norms and expectations. This knowledge lets students know where and how hard/soft skills are used. Our results also suggest practitioners are concerned with the prevailing individualistic approach to the higher education system and traditional architectural teaching methods, instead suggesting a more industry-aligned collaborative disposition.Originality/valueBy expanding the employability discourse beyond hard/soft skills, the results of this research provide an opportunity for architectural curriculum renewal in line with industry expectations.
Research on the new method for visualizing bendability testing of fabrics in multiple directions
Authors: Jiang Xin , Liu Chengxia 
Published: May 2024

PurposeThe current bending test method can only test the bending performance of fabric in one direction at a time. It is not possible to directly observe the bending morphology of fabrics in different directions, and it is necessary to cut samples and repeat the test several times, which takes more time. For this situation, a multidirectional visualization of the fabric bending test method is proposed, using which multiple results can be obtained at one time and the fabric bending can be visualized.Design/methodology/approachAbout 17 fabrics are tested using a self-designed device. The fabrics are cut into special triangles and multiple sets of results in three directions are obtained at once using the device. The experimental specimens are photographed from the above and the transverse elongation length, bending projection area and circumference are extracted after image processing.FindingsThe results show that the correlation coefficients of transverse elongation, bending projected area and circumference are good with the bending length measured by the cantilever method. In which, all three indicators are positively correlated with the bending length. This indicates the good feasibility of the new method.Originality/valueThis method can get the bending index of fabrics in three directions, with five samples in each direction at one time. Meanwhile, it can also visualize the flexural differences between different fabrics and directions of the same fabric. It can provide more efficient testing means for the textile testing field, and the testing efficiency is 15 times of the existing method, which has better theoretical significance and practical values.