bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bio-orthogonal chemistry-based conjugation strategy facilitates investigation of impacts of s2U, s4U, m1A and m6A guide RNA modifications on CRISPR activity
Authors: Hoy Alyssa , Zheng Ya Ying , Sheng Jia , Royzen Maksim 
Published: June 2022

SummaryThe CRISPR-Cas9 system is an important genome editing tool that holds enormous potential towards treatment of human genetic diseases. Clinical success of CRISPR technology is dependent on incorporation of modifications into the single guide RNA (sgRNA). However, chemical synthesis of modified sgRNAs, which are over 100 nucleotides in length, is difficult and low-yielding. We developed a conjugation strategy that utilized bio-orthogonal chemistry to efficiently assemble functional sgRNAs containing nucleobase modifications. The described approach entails the chemical synthesis of two shorter RNA oligonucleotides: a 31-mer containing tetrazine (Tz) group and a 70-mer modified with a trans-cyclooctene (TCO) moiety. The two oligonucleotides were conjugated to form functional sgRNAs. The two-component conjugation methodology was utilized to synthesize a library of sgRNAs containing nucleobase modifications such as m1A, m6A, s2U and s4U. The impacts of these RNA modifications on overall CRISPR activity was investigated in vitro and in Cas9-expressing HEK293T cells.
Sequence-sensitive elastic network captures dynamical features necessary for miR-125a maturation
Authors: Mailhot Olivier , Frappier Vincent , Major François , Najmanovich Rafael 
Published: June 2022

AbstractThe Elastic Network Contact Model (ENCoM) is a coarse-grained normal mode analysis (NMA) model unique in its all-atom sensitivity to the sequence of the studied macromolecule and thus to the effect of mutations. We adapted ENCoM to simulate the dynamics of ribonucleic acid (RNA) molecules, benchmarked its performance against other popular NMA models and used it to study the 3D structural dynamics of human microRNA miR-125a, leveraging high-throughput data on the maturation efficiency of over 26 000 sequence variants. We also introduce a novel way of using dynamical information from NMA to train multivariate linear regression models, with the purpose of highlighting the most salient contributions of dynamics to function. ENCoM has a similar performance profile on RNA than on proteins when compared to the Anisotropic Network Model (ANM), the most widely used coarse-grained NMA model; it has the advantage on predicting large-scale motions while ANM performs better on B-factors prediction. A stringent benchmark from the miR-125a maturation dataset, in which the training set contains no sequence information in common with the testing set, reveals that ENCoM is the only tested model able to capture signal beyond the sequence. This ability translates to better predictive power on a second benchmark in which sequence features are shared between the train and test sets. When training the linear regression model using all available data, the dynamical features identified as necessary for miR-125a maturation point to known patterns but also offer new insights into the biogenesis of microRNAs. Our novel approach combining NMA with multivariate linear regression is generalizable to any macromolecule for which relatively high-throughput mutational data is available.AvailabilityENCoM is open source software part of the NRGTEN package available athttps://github.com/gregorpatof/nrgten_packageContactrafael.najmanovich@umontreal.ca,francois.major@umontreal.ca
Starvation Induces Diverse Autophagic Response in Cardiomyocytes and Noncardiomyocytes
Authors: He Xi-Biao , Huang Haozhi , Wu Yi , Guo Fang 
Published: June 2022

ABSTRACTCardiac autophagy serves as a potential mechanism to be genetically, epigenetically and pharmaceutically manipulated to prevent or alleviate pathological conditions in heart diseases. One of the complexities of this manipulation comes from the cellular heterogeneity of the heart. In this study, we assessed the dynamics of nutrient deprivation-induced autophagy activation in four major cardiac cell types in vitro and in vivo and found a major difference between cardiomyocyte and other three types of noncardiomyocyte. In comparison to the constant increase and maintenance of autophagic activity in noncardiomyocytes, cardiomyocyte undergoes rapid gain and loss of autophagic activity. This difference contributes to at least two aspects of cardiomyocyte pathophysiology: high vulnerability to nutrient deprivation-induced cell death and unresponsiveness to pharmaceutical regulation of autophagy. Our present findings support a cell type-specific targeting of autophagy for therapeutic intervention of cardiac diseases.
Dynamics of mRNA fate during light stress and recovery: from transcription to stability and translation
Authors: Smith Aaron B. , Ganguly Diep R. , Moore Marten , Bowerman Andrew F. , Janapala Yoshika , Shirokikh Nikolay , Pogson Barry J. , Crisp Peter A 
Published: June 2022

AbstractTranscript stability is an important determinant of its abundance and, consequently, translation. However, it is unclear the extent to which it is modulated between environmental conditions. We previously hypothesised that recovery-induced transcript destabilisation facilitated a phenomenon of rapid recovery gene down-regulation (RRGD) inArabidopsis thalianafollowing stress, based on mathematical calculations to account for ongoing transcription. Here, we test this hypothesis, and investigate processes regulating transcript abundance and fate, by quantifying changes in transcription, stability, and translation before, during, and after light stress. We adapt syringe infiltration to apply a transcriptional inhibitor to soil-grown plants in combination with stress. Compared to measurements in juvenile plants and cell culture, we find reduced stability in a range of transcripts. We also observe transcript destabilisation during light stress, followed by stabilisation upon recovery. Alongside fast transcriptional shut-off in recovery, this destabilisation appears to facilitate RRGD. Translation was dynamic over the course of light stress and recovery, with substantial transcript-specific increases in ribosome-association, independent of changes in total transcript abundance, observed after 30 minutes of light stress. Taken together, we provide evidence for the combinatorial regulation of transcription, stability, and translation that occurs to facilitate responses to light stress and recovery.
An Optogenetic Toolkit for Light-Inducible Antibiotic Resistance
Authors: Sheets Michael B. , Dunlop Mary J. 
Published: June 2022

AbstractAntibiotics are a key control mechanism for synthetic biology and microbiology. Resistance genes are used to select desired cells and regulate bacterial populations, however their use to-date has been largely static. Precise spatiotemporal control of antibiotic resistance could enable a wide variety of applications that require dynamic control of susceptibility and survival. Here, we use light-inducible Cre recombinase to activate expression of drug resistance genes in Escherichia coli. We demonstrate light-activated resistance to four antibiotics: carbenicillin, kanamycin, chloramphenicol, and tetracycline. Cells exposed to 465 nm blue light survive in the presence of lethal antibiotic concentrations, while those kept in the dark do not. To optimize resistance induction ranges, we characterize the impact of the promoter, ribosome binding site, and enzyme variant strength using chromosome and plasmid-based constructs. Using time-lapse microscopy, we further show resistance activation dynamics. These optogenetic drug resistance tools pave the way for spatiotemporal control of cell survival.
High-content quantitative high-throughput screening identifies a cell cycle-associated signaling cascade that regulates a multienzyme metabolic assembly for glucose metabolism
Authors: Schmitt Danielle L. , Dranchak Patricia , Parajuli Prakash , Blivis Dvir , Voss Ty , Kohnhorst Casey L. , Kyoung Minjoung , Inglese James , An Songon 
Published: June 2022

AbstractWe have previously demonstrated that human liver-type phosphofructokinase 1 (PFK1) recruits other rate-determining enzymes in glucose metabolism to organize multienzyme metabolic assemblies, the glucosomes, in human cells. However, it has remained largely elusive how glucosomes are reversibly assembled and disassembled to functionally regulate glucose metabolism in human cells. We developed a high-content quantitative high-throughput screening (qHTS) assay to evaluate the impact of small molecule libraries on the formation of PFK1-mediated glucosome assemblies from stably transfected HeLa Tet-On cells. Initial qHTS with a library of pharmacologically active compounds directed following efforts to kinase-inhibitor enriched collections. Consequently, three active compounds that were known to inhibit cyclin-dependent kinase 2, ribosomal protein S6 kinase and Aurora kinase A, respectively, were identified and further validated under high-resolution fluorescence single-cell microscopy. Subsequent knockdown studies using small-hairpin RNAs confirmed an active role of Aurora kinase A on the formation of PFK1 assemblies in HeLa cells. Importantly, all the identified protein kinases here have been investigated as key signaling nodes of one specific cascade that controls cell cycle progression in human cells. Collectively, our qHTS approaches unravel a cell cycle-associated signaling cascade that regulates the formation of PFK1-mediated glucosome assembly in human cells.
Demystifying the role of absorptive capacity in achieving innovation-based performance: model development and empirical validation
Authors: Bindra Sunali , Sharma Deepika , Mishra Hari Govind , Bhardwaj Rohit 
Published: June 2022

PurposeThe purpose of this study is to explicate the relationship between knowledge-based dynamic capacities (KBDC) and innovation-based performance (INPF) in information technology (IT) firms in India by examining the mediating impact of absorptive capacity (ABCP). The paper aims to determine whether and how the ABCP of the firms is recognized as the essential facilitator of INPF.Design/methodology/approachA survey of 511 respondents from Indian IT employees at the upper and middle management levels was undertaken. In this study, the partial least squares (PLS) technique explored the causal links between constructs with the use of the software application SMART-PLS 3.0.FindingsThe outcomes of this study proved the existence of a statistically significant relationship between the ABCP and INPF of information technology firms. Furthermore, ABCP's influence as a mediator between KBDC and INPF is significant. Therefore, findings imply that ABCP mediates the relationship between KBDC and INPF, however, only to some extent.Research limitations/implicationsWith the dynamism of the global market, the research has made significant gains in illustrating the criticality of ABCP for strengthening its KBDC in a much-needed Indian context. Therefore, following the recommendations and findings of this study, practitioners should concentrate on strengthening both ABCP and KBDCs to improve their INPF. To do this, managers must proactively organize their resources, procedures, and structure to promote knowledge absorption and dissemination, fostering innovation.Originality/valueIt is a ground-breaking study that proposes that the ABCP plays a crucial role in enhancing the INPF of the firms. The software industry will likely benefit from this study by understanding ABCP's potential impact on its INPF and designing knowledge management methods accordingly.
Community of practice: the making of knowledge dynamic in intangible cultural heritage
Authors: Lee Louisa Yee Sum 
Published: June 2022

Purpose
This study aims to understand how a community of practice (CoP) facilitates the knowledge spiral of intangible cultural heritage (ICH) in tourist destinations.

Design/methodology/approach
This case study focuses on Cantonese opera, a representative example of the ICH of Hong Kong. Narrative inquiry with eight CoP members was used in this study.

Findings
The CoP members believed that the city has unique and quality tourism knowledge. They used their professional expertise in the domains of creating, collecting and sharing both explicit and tacit knowledge. With the strategic goal of creating a sustainable competitive advantage, CoP act as a kernel in knowledge creation by converting explicit knowledge into tacit knowledge and vice versa.

Originality/value
This study uses the knowledge spiral model to understand knowledge creation, and it contributes to the sparse literature on knowledge management in the field of tourism, especially the role of CoP. It addressed a gap in the literature pertaining to knowledge creation and ICH.
Evaluating the impact of a prison smoking ban on the cardiovascular health of men in a UK prison
Authors: Perrett Stephanie E. , Craddock Christie , Dunseath Gareth , Shankar Giri , Luzio Stephen , Gray Benjamin J. 
Published: June 2022

Purpose
Smoking rates are known to be higher amongst those committed to prison than the general population. Those in prison suffer from high rates of comorbidities that are likely to increase their risk of cardiovascular disease (CVD), making it more difficult to manage. In 2016, a tobacco ban began to be implemented across prisons in England and Wales, UK. This study aims to measure the effect of the tobacco ban on predicted cardiovascular risk for those quitting smoking on admission to prison.

Design/methodology/approach
Using data from a prevalence study of CVD in prisons, the authors have assessed the effect of the tobacco ban on cardiovascular risk, using predicted age to CVD event, ten-year CVD risk and heart age, for those who previously smoked and gave up on admission to prison.

Findings
The results demonstrate measurable health gains across all age groups with the greatest gains found in those aged 50 years and older and who had been heavy smokers. Quitting smoking on admission to prison led to a reduced heart age of between two and seven years for all participants.

Originality/value
The data supports tobacco bans in prisons as a public health measure to reduce risk of CVD. Interventions are needed to encourage maintenance of smoking cessation on release from prison for the full health benefits to be realised.
Which leadership processes encourage sustainable transitions within universities?
Authors: Azizi Leyla 
Published: June 2022

Purpose
The implementation of sustainability-related policies at universities has been marked by a greater sense of urgency in recent years. Despite this emerging trend, it is still unclear which leadership processes, at which levels and which theoretical concepts encourage sustainable transitions within universities.

Design/methodology/approach
This study aims to offer a systematic literature review of the existing literature on sustainability-related leadership processes, levels and theories that encourage the transformation of universities, aimed at providing guidance on this topic; uncovering gaps in the literature; and finding new paths for future research.

Findings
Leadership processes in the context of sustainability-related transitions have been approached in a rather fragmented way in the literature, and the scientific field would benefit from more in-depth and longitudinal studies. In total, this study identifies 95 processes that are related to 17 aspects of universities’ transitions.

Research limitations/implications
The various leadership levels are involved in transition processes at different stages. The theories of distributed and sustainability leadership seem to be the most frequently used theories in the literature.

Practical implications
Structuring and defining leadership processes, levels and theories can lead to a better understanding of the dynamics of the transition process and, in a broader sense, of the process of sustainability integration in higher education. A better knowledge of how such a transition develops could contribute to the enhancement of existing sustainable development strategy and policy.

Originality/value
By focusing on an underresearched topic through a theoretical perspective of leadership theories, this study contributes to literature pertaining to leadership levels and processes involved in sustainability transitions of universities.
Enterprising tendency and entrepreneurial performance of indigenous Dayak women entrepreneurs in Sarawak, Malaysia
Authors: Keling William , Yap Ching Seng , Ho Poh Ling 
Published: June 2022

Purpose
This study aims to examine entrepreneurial performance differences between indigenous Dayak women entrepreneurs of their high versus low enterprising tendency in Sarawak, Malaysia.

Design/methodology/approach
A quantitative approach was used for data collection and analysis. The population of this study was the indigenous women entrepreneurs in Sarawak, Malaysia. Primary data were collected from 129 indigenous women entrepreneurs using convenience sampling. The survey instrument for measuring enterprising tendency and entrepreneurial performance was adopted from the relevant literature. Data were analyzed using independent t-tests in Statistical Packages for Social Science.

Findings
This study found that indigenous women entrepreneurs with higher enterprising tendencies performed better than those with lower enterprising tendencies. A significant difference was found between entrepreneurs with a higher enterprising tendency and those with a lower enterprising tendency in three of the five entrepreneurial attributes: need for achievement, creative tendency and calculated risk-taking. Nevertheless, no significant difference was observed in need for autonomy and internal locus of control between the two groups of indigenous women entrepreneurs.

Originality/value
Very few studies are available in the Malaysian context explicitly concerning women entrepreneurs in general and indigenous Dayak women in specific. Therefore, this study provides novel insights into the relationship between enterprising tendency and entrepreneurial performance among indigenous Dayak women entrepreneurs in Malaysia.
Vaccine network design to maximize immunization coverage
Authors: Goentzel Jarrod , Russell Timothy , Carretti Henrique Ribeiro , Hashimoto Yuto 
Published: June 2022

PurposeThe COVID-19 pandemic has forced countries to consider how to reach vulnerable communities with extended outreach services to improve vaccination uptake. The authors created an optimization model to align with decision-makers' objective to maximize immunization coverage within constrained budgets and deploy resources considering empirical data and endogenous demand.Design/methodology/approachA mixed integer program (MIP) determines the location of outreach sites and the resource deployment across health centers and outreach sites. The authors validated the model and evaluated the approach in consultation with UNICEF using a case study from The Gambia.FindingsResults in The Gambia showed that by opening new outreach sites and optimizing resource allocation and scheduling, the Ministry of Health could increase immunization coverage from 91.0 to 97.1% under the same budget. Case study solutions informed managerial insights to drive gains in vaccine coverage even without the application of sophisticated tools.Originality/valueThe research extended resource constrained LMIC vaccine distribution modeling literature in two ways: first, endogenous calculation of demand as a function of distance to health facility location enabled the effective design of the vaccine network around convenience to the community and second, the model's resource bundle concept more accurately and flexibly represented complex requirements and costs for specific resources, which facilitated buy-in from stakeholders responsible for managing health budgets. The paper also demonstrated how to leverage empirical research and spatial analysis of publicly available demographic and geographic data to effectively represent important contextual factors.
Board dynamics and relational tensions in the English NHS foundation trusts
Authors: Manzoor Humera , Nocker Manuela , Rashid Mehboob ur , Ghani Usman 
Published: June 2022

PurposeThis study explores interactional dynamics and relational tensions within English NHS Foundation Trust board meetings that are influenced by governance structure and the board composition.Design/methodology/approachThis paper draws upon an ethnonarrative approach to enable the understanding of the nuances of boardroom interactions. Data was collected through participant observation of board of directors’ and board of governors’ meetings and narrative interviews from directors and governors of two NHS Foundation Trusts. Data was analyzed through thematic narrative analysis to enable the identification and understanding of the patterns and the hidden tensions in boards.FindingsFindings reveal that board interactions are influenced strongly by the nexus of structural, contextual and human elements of governance. Three main findings are highlighted: a lack of clarity of the governors’ and chairpersons’ roles which create ambiguities within board processes; the large size of the board of governors disrupts meaningful discussions in board meetings; the unacceptability and avoidance of governors’ accountability by the directors creates a struggle for supremacy and legitimacy in boards.Research limitations/implicationsFuture research can explore both the positive and negative outcomes of board behaviors, which are influenced by the perceived built-in tensions in governance structures. In addition, access to other spaces of governance, such as, subcommittee meetings and private board meetings can further enrich our understanding of board dynamics.Originality/valueThis study attempts to uncover the neglected modes of interactions within boards through a combination of two disparate perspectives: board structures/composition and interactions through an ethnonarrative approach.
Stevens–Johnson syndrome and toxic epidermal necrolysis associated with increased risk of developing psychiatric disorders: A retrospective population‐based cohort study in Taiwan
Authors: Chiang Chien‐Ping , Hung Chih‐Tsung , Chen Yi‐Hsien , Chen Chih‐Yu , Soong Chen‐Yeu , Liu Sheng‐Wen , Liu Hsi‐Ling , Ma Jun , Chung Chi‐Hsiang , Tsao Chang‐Huei , Sun Chien‐An , Chien Wu‐Chien , Wang Wei‐Ming 
Published: June 2022

AbstractStevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life‐threatening adverse reactions to drugs and psychological sequelae are also observed to follow the trauma of widespread epidermal necrolysis. To delineate the association between SJS and TEN, and psychiatric disorders, we conducted a retrospective population‐based cohort study by including 212 patients diagnosed with first‐time SJS or TEN in Taiwan between 2000 and 2013 and 669 population controls. Adjusted hazard ratios were calculated after adjusting for sex, age, comorbidity in the form of Charlson comorbidity index, and facility level of care. Overall, SJS or TEN was associated with an increased risk of developing psychiatric disorders including schizophrenia, major depressive disorder, mania, anxiety, and bipolar with an adjusted hazard ratio of 1.392 (95% CI, 1.192–1.625; p < 0.001). Particularly, the adjusted hazard ratios of psychiatric disorders were 1.290 (95% CI, 1.105–1.506; p < 0.001) for SJS and 1.855 (95% CI, 1.587–2.167; p < 0.001) for TEN.