bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Function of Transcription Factor TTF1 in UV Mediated DNA Damage Repair in Mammalian Cells
Authors: Tiwari Kumud , Bose Snehendu , Mishra Neelu , Singh Samarendra Kumar 
Published: May 2023

AbstractVarious DNA repair machineries have evolved in the cell to maintain the integrity of the genome for proper functioning of the same. Repair of ultraviolet (UV) irradiation mediated DNA damage occurs by nucleotide excision repair pathway through transcription coupled repair (TCR), a process in which the damage is repaired on transcriptionally active genic regions. This process requires various protein complexes including heterodimer DNA Damage Binding 1 (DDB1) protein. Defects in TCR have been found in patients with mutations in the Cockayne syndrome (CS) group A and group B genes and in the Xeroderma pigmentosum (XP) group G gene. Transcription factors (TFs) play a very important role in regulation of TCR system, especially those TFs which binds to DNA at specific loci. Several TFs have been shown to modulate the repair of photolesions either by inducing or inhibiting the TCR. However, the mechanism behind their action is not very clear. Mammalian TTF1 is an essential multifunctional transcription factor involved in transcription initiation, termination, DNA fork blockage, chromatin remodelling etc., and has been shown to interact with CSB protein. Hence, to discover its role in TCR and to identify its interaction partners, we purified this protein and did a pull-down assay with HEK293T cell lysate followed by LC-MS and discovered DDB1 as one of its major interactors. This established our confidence that TTF1 protein might be playing a critical role in TCR. Further, we discovered that, upon UV mediated DNA damage in HEK293T cells the expression of TTF1 is significantly induced and is co-localized withγH2AX protein. To our surprise, we found that after knockdown of TTF1, DDB1 level decreases in HEK293T cells while knockdown of DDB1, increases TTF1 level in the cells. Hence, our study opens up a new avenue towards exploring a noble function of the transcription factor TTF1, which in turn could establish the potential to develop therapeutics towards cancers and other diseases.
Deletion of miR-146a enhances therapeutic protein restoration in model of dystrophin exon skipping
Authors: McCormack Nikki M. , Calabrese Kelsey A. , Sun Christina M. , Tully Christopher B. , Heier Christopher R. , Fiorillo Alyson A. 
Published: May 2023

AbstractDuchenne muscular dystrophy (DMD) is a progressive muscle disease caused by the absence of dystrophin protein. One current DMD therapeutic strategy, exon skipping, produces a truncated dystrophin isoform using phosphorodiamidate morpholino oligomers (PMOs). However, the potential of exon skipping therapeutics has not been fully realized as increases in dystrophin protein have been minimal in clinical trials. Here, we investigate how miR-146a-5p, which is highly elevated in dystrophic muscle, impacts dystrophin protein levels. We find inflammation strongly induces miR-146a in dystrophic, but not wild-type myotubes. Bioinformatics analysis reveals that the dystrophin 3′UTR harbors a miR-146a binding site, and subsequent luciferase assays demonstrate miR-146a binding inhibits dystrophin translation. In dystrophin-nullmdx52mice, co-injection of miR-146a reduces dystrophin restoration by an exon 51 skipping PMO. To directly investigate how miR-146a impacts therapeutic dystrophin rescue, we generatedmdx52with body-wide miR-146a deletion (146aX). Administration of an exon skipping PMO via intramuscular or intravenous injection markedly increases dystrophin protein levels in146aXversusmdx52muscles; skipped dystrophin transcript levels are unchanged, suggesting a post-transcriptional mechanism-of-action. Together, these data show that miR-146a expression opposes therapeutic dystrophin restoration, suggesting miR-146a inhibition warrants further research as a potential DMD exon skipping co-therapy.
Alpha-180 spin-echo based line-scanning method for high resolution laminar-specific fMRI
Authors: Choi Sangcheon , Hike David , Pohmann Rolf , Avdievich Nikolai , Gomez-Cid Lidia , Man Weitao , Scheffler Klaus , Yu Xin 
Published: May 2023

ABSTRACTLaminar-specific functional magnetic resonance imaging (fMRI) has been widely used to study circuit-specific neuronal activity by mapping spatiotemporal fMRI response patterns across cortical layers. Hemodynamic responses reflect indirect neuronal activity given limit of spatial and temporal resolution. Previous gradient-echo based line-scanning fMRI (GELINE) method was proposed with high temporal (50 ms) and spatial (50 µm) resolution to better characterize the fMRI onset time across cortical layers by employing 2 saturation RF pulses. However, the imperfect RF saturation performance led to poor boundary definition of the reduced region of interest (ROI) and aliasing problems outside of the ROI. Here, we propose α (alpha)-180 spin-echo-based line-scanning fMRI (SELINE) method to resolve this issue by employing a refocusing 180° RF pulse perpendicular to the excitation slice. In contrast to GELINE signals peaked at the superficial layer, we detected varied peaks of laminar-specific BOLD signals across deeper cortical layers with the SELINE method, indicating the well-defined exclusion of the large drain-vein effect with the spin-echo sequence. Furthermore, we applied the SELINE method with 200 ms TR to sample the fast hemodynamic changes across cortical layers with a less draining vein effect. In summary, this SELINE method provides a novel acquisition scheme to identify microvascular-sensitive laminar-specific BOLD responses across cortical depth.
Quantitative Comparison of Presenilin Protein Expression Reveals Greater Activity of PS2-γ-Secretase
Authors: Eccles Melissa , Main Nathan , Sabale Miheer , Roberts-Mok Brigid , Agostino Mark , Groth David , Fraser Paul E. , Verdile Giuseppe 
Published: May 2023

Abstractγ-Secretase processing of APP has long been of interest in the pathological progression of Alzheimer’s disease (AD) due to its role in the generation of amyloid-β. The catalytic component of the enzyme are the presenilins of which there are two homologues, Presenilin-1 (PS1) and Presenilin-2 (PS2). The field has focussed on the PS1 form of this enzyme, as it is typically considered the more active at APP processing. However, much of this work has been completed without appropriate consideration of the specific levels of protein expression of PS1 and PS2. We propose that expression is an important factor in PS1- and PS2-γ-secretase activity, and that when this is considered, PS1 does not have greater activity than PS2. We developed and validated tools for quantitative assessment of PS1 and PS2 protein expression levels to enable direct comparison of PS protein in exogenous and endogenous expression systems, in HEK-293 PS1 and/or PS2 knockout cells. We show that exogenous expression of Myc-PS1-NTF is 5.5-times higher than and Myc-PS2-NTF. Quantitating endogenous PS protein levels using a novel PS1/2 fusion standard we developed showed similar results. When the marked difference in PS1 and PS2 protein levels is considered, we show that compared to PS1-γ-secretase, PS2-γ-secretase has equal or more activity on APP and Notch1. This study has implications for understanding the PS1 and PS2 specific contributions to substrate processing, and their potential influence in AD pathogenesis.
Hot-wiring dynein-2 uncovers roles for IFT-A in retrograde train assembly and motility
Authors: Gonçalves-Santos Francisco , De-Castro Ana R. G. , Rodrigues Diogo R. M. , De-Castro Maria J. G. , Gassmann Reto , Abreu Carla M. C. , Dantas Tiago J. 
Published: May 2023

SUMMARYIntraflagellar transport (IFT) trains, built around IFT-A and IFT-B complexes, are carried by opposing motors to import and export ciliary cargo. While transported by kinesin-2 on anterograde IFT trains, the dynein-2 motor adopts an autoinhibitory conformation until it needs to be activated at the ciliary tip to power retrograde IFT. Growing evidence has linked the IFT-A complex to retrograde IFT; however, its roles in this process remain unknown.Here, we used CRISPR/Cas9-mediated editing to disable the dynein-2 autoinhibition mechanism inCaenorhabditis elegans, and assessed its impact on IFT with high-resolution live imaging and photobleaching analyses. Remarkably, this dynein-2 “hot-wiring” approach reignites retrograde motility inside IFT-A-deficient cilia, without triggering tug-of-war events. In addition to providing functional evidence that multiple mechanisms maintain dynein-2 inhibited during anterograde IFT, our data uncover key roles for IFT-A in: mediating motor-train coupling during IFT turnaround; promoting retrograde IFT initiation; and modulating dynein-2 retrograde motility.Highlights- Hot-wiring mutations enable dynein-2 to undergo retrograde movement in IFT-A-deficient cilia- Disabling dynein-2 autoinhibition reveals that multiple mechanisms restrain dynein-2 activity during anterograde IFT- IFT-A promotes retrograde IFT initiation and efficient dynein-2 motility- IFT-A mediates dynein-2 coupling to retrograde IFT trains
The E3 Ubiquitin Ligase Nedd4L Acts as a Checkpoint Against Activation in Quiescent Muscle Stem Cells
Authors: Blackburn Darren M. , Sahinyan Korin , Hernández-Corchado Aldo , Lazure Felicia , Richard Vincent , Raco Laura , Zahedi René P. , Borchers Christoph H. , Lepper Christoph , Kawabe Hiroshi , Jahani-Asl Arezu , Najafabadi Hamed S. , Soleimani Vahab D. 
Published: May 2023

SummaryAdult stem cells play a critical role in tissue repair and maintenance. In tissues with slow turnover, including skeletal muscle, these cells are maintained in a mitotically quiescent state yet remain poised to re-enter the cell cycle to replenish themselves and regenerate the tissue. Using a multiomics approach we identify the PAX7/NEDD4L axis as a checkpoint against muscle stem cell activation in homeostatic skeletal muscle. Our findings demonstrate that PAX7 transcriptionally activates the E3 ubiquitin ligase Nedd4L and that the conditional genetic deletion of Nedd4L impairs muscle stem cell quiescence, with an upregulation of cell cycle and myogenic differentiation genes. Loss of Nedd4L in muscle stem cells results in the expression of DCX which is only expressed during theirin vivoactivation. Together, this data establishes that the ubiquitin proteasome system, mediated by Nedd4L, is a key regulator of the muscle stem cell quiescent state in non-injured skeletal muscle.Highlights-General inhibition of the ubiquitin proteasome system with MG132 results in muscle stem cells (MuSCs) breaking quiescence.-The E3 ubiquitin ligase Nedd4L is a transcriptional target of Pax7.-The Pax7/Nedd4l axis restricts MuSC activation in homeostatic skeletal muscle.-Genetic deletion of Nedd4L induces MuSCs’ transition towards activation.
An evaluation of the environmental values, beliefs, norms, and behaviors of sport management students in higher education institutions
Authors: Pelcher Jamee , Trendafilova Sylvia , Graham Jeffrey Alexander 
Published: May 2023

Purpose
The purpose of this study is to evaluate the environmental values, beliefs, norms and behaviors of students in higher education institutions across North America, more specifically, undergraduate and graduate students in sport management programs.

Design/methodology/approach
The research was framed around Stern et al.’s (1999) value-belief-norm theory, which provides an explanation of the causes of the broad predisposition toward pro-environmental behavior. Furthermore, it was an extension of the work conducted by Casper and Pfahl (2012). Data collection was based on an online survey, comprising questions related to the students’ values, beliefs, norms and behaviors in relation to the natural environment.

Findings
Results indicated strong agreeance with the biospheric environmental statements that reflect the individuals’ personal ecological values, illustrating a moderate agreement with the degree of responsibility and obligation felt by the student to take environmental action. Findings also suggested that students hold sport organizations to a higher level of environmentalism than their personal environmental sustainability practices. Both groups, undergraduate and graduate students, have values, beliefs and norms moderately connected to pro-environmental stances.

Practical implications
It would be beneficial for educators to use this information as baseline from which to build and re-design their classes.

Originality/value
It would be beneficial for educators to use this information as baseline from which to build and re-design their classes. This study provides valuable information for faculty to create and frame curricula to better prepare future professionals for a career in the sports industry.
Flexible working during the COVID-19 pandemic: gains and strains in a Chinese state-owned organisation
Authors: Ren Xiaoni , Xu Hanlin 
Published: May 2023

Purpose
This study aims to identify and analyse the gains and strains associated with flexible working practices (FWPs) introduced and adopted prior to and during the pandemic and consider how these experiences are likely to shape the future of workplace flexibility post-pandemic.

Design/methodology/approach
A case study research strategy was adopted to explore the FWPs implemented by a state-owned organisation in the Chinese publishing industry. A mixed data collection method was used. Quantitative data was collected from 50 valid questionnaires, which was followed by 7 qualitative interviews to gain rich insights into the availability and effectiveness of various FWPs and associated benefits and drawbacks.

Findings
While the results confirm positive effects FWPs have on employee engagement and retention and on business continuity and employee well-being during the pandemic, the empirical analysis highlights the performance-driven patterns in use and impacts of some FWPs, which caused concerns and dilemmas. Besides the increasing intense market competition, the changing face of state-owned enterprises and managerial attitudes have been found to have significant effects on the use of FWPs.

Originality/value
This paper has contributed to a better understanding of flexible working in an under-researched setting, reflected in changes before and during the pandemic, offering an insight into the commercialised nature of flexible working in the Chinese context. It has implications for organisations and HR practitioners as they envision future workplace flexibility.
Embracing green supply chain collaboration through technologies: the bridging role of advanced manufacturing technology
Authors: Akhtar Faheem , Huo Baofeng , Wang Qianwen 
Published: May 2023

Purpose
The implementation of green collaboration has evolved from the interfirm level to the supply chain level, which requires more participation in information and manufacturing technologies. Despite many efforts to green supply chain collaboration (GSCC), the research on how to enhance it from a technological perspective remains unclear. Thus, this study aims to address this gap by exploring how to enhance green supplier, internal and customer collaboration through using information technology (IT) and advanced manufacturing technology (AMT), which further accelerates environmental and economic performance.

Design/methodology/approach
This study was conducted based on survey data collected from 213 manufacturing firms from different industries. The direct effects of the conceptual model were tested using the method of structural equation modeling (SEM), whereas the bootstrapping method tested the mediation effects of AMT between IT and GSCC.

Findings
The results show that green supplier collaboration (GSC) is significantly associated with environmental performance, while green customer collaboration (GCC) is positively related to economic performance. Green internal collaboration not only enhances green supplier and customer collaboration but also boosts environmental and economic performance. IT directly improves green internal collaboration but is negatively related to GSC and insignificantly related to GCC. However, AMT not only enhances green internal, supplier and customer collaboration but also mediates the relationship between IT and green supplier and customer collaboration.

Originality/value
This study offers comprehensive and novel insights into GSCC from a technological perspective, giving rise to meaningful contributions to green practices for both scholars and practitioners.
Monetary policy effectiveness in Asian developing economies: the moderating role of financial sector development
Authors: Khan Muhammad Azam , Khan Zulfiqar , Saleem Sardar Fawad 
Published: May 2023

PurposeThis study aims to explore the impact of monetary policy on bank lending rate with the moderating effects of financial sector development for eight Asian developing economics.Design/methodology/approachThis study uses panel autoregressive distributed lag/pooled mean group estimation over the period ranging from 1980 to 2020.FindingsThe empirical results exhibit an inverse link between monetary policy measured by broad money supply on the bank lending rate, indicating that the increase in the money supply by the central bank lowers the demand for loans and thereby lowers the cost of loan. Moreover, financial sector development decreases the lending rate and thus lowers cost of loan. It is also noted that the interactive term of monetary policy by lending broad money supply and financial sector development showed a positive impact on the lending rate in selected Asian developing countries during the period under the study.Practical implicationsThe outcomes have many relevant policy implications that stronger financial development sector contributes to the efficiency of monetary policy. Regulators and policymakers are therefore recommended to pursue greater financial sector development to lower the cost for fund searchers and to lower the cost of loans, money supply increase is suggested.Originality/valueThis study contributes to the extant literature on the factors affecting lending rate with the prime aims of monetary policy effectiveness. This study also included financial sector development with some other variables and an interactive term of monetary policy with financial development to have new insight impact of both on the lending rate in developing Asian economies.
Do the macro and global economic factors drive the nonperforming loans in GCC economies?
Authors: Kumar Mukesh , Al-Romaihi Muna Ahmed , Aktan Bora 
Published: May 2023

Purpose
The current study aims to investigate the determinants of nonperforming loans (NPLs) in the GCC economies during the period spanning 2000 to 2018. It also examines whether the worldwide financial crisis of 2007–2008, which brought the issue of non–performing loans to the greater attention of academics and policymakers, had a substantial impact on NPLs in this region.

Design/methodology/approach
The sample consists of 53 conventional banks from GCC countries, and the basic data for the study is obtained from various sources such as Bankscope, IMF World Economic Outlook, World Bank and Chicago Board of Options Exchange Market Volatility Index. The estimations were done by dynamic panel data regression modeling using system generalized methods of moments.

Findings
The findings reveal that both, the non-oil real GDP growth rate and inflation have favorable effects on NPLs. On the other hand, domestic credit to the private sector and the volatility index have an adverse effect on NPLs. Furthermore, the period-wise analysis shows that the relevance and significance of the determinants of NPLs vary between the precrisis and postcrisis periods. It is also reflected through the intercept dummy, which is found to be significant, indicating that the financial crisis, as a global economic factor, had a significant impact on NPLs. A number of robustness tests are applied, which indicate that the results are mostly robust and consistent in terms of the significance of the explanatory variables and the direction of their relationship with the dependent variable.

Practical implications
Policymakers and bank authorities must strive to maintain a healthy economy and implement macroprudential policies to improve the financial stability of banks and reduce credit risk.

Originality/value
To the best of the authors’ knowledge, this is likely the first study that empirically investigates the influence of the financial crisis on NPLs in the context of GCC economies. In addition, the research spans 19 years to produce more conclusive results.
Exploring the factors influencing building sustainability of low-cost low-rise residential towards user satisfaction
Authors: Norazman Norsafiah , Mohd Nashruddin Siti Nurul Asma’ , Che-Ani Adi Irfan 
Published: May 2023

Purpose
Urban population growth has increased housing density, which has expanded the construction of low-cost low-rise residential in urban areas. Good building performance and effective low-cost low-rise residential quality lead to higher user satisfaction and improve building sustainability. This study aims to focus on the factors influencing the sustainability of low-cost low-rise residential in the West Malaysia urban area to assess resident satisfaction.

Design/methodology/approach
A mixed-mode approach with both qualitative and quantitative were used in this study. Semi-structured interviews were conducted with 12 stakeholders to identify the common factors influencing sustainability in low-cost low-rise residential. Subsequently, questionnaire surveys were formed and distributed among building users to determine the satisfaction level with low-cost low-rise residential building performance.

Findings
The finding demonstrates that accessibility is the key factor to achieving sustainability of low-cost low-rise residential. The finding also related to the factor that influences both stakeholders and building user satisfaction levels. This study also identifies key areas that require attention to improve user satisfaction with building sustainability and building performance of low-cost low-rise residential.

Originality/value
This study aims to determine stakeholder and building user satisfaction levels in relation to the sustainable building factor. A few indicators have been set up to identify the factors that most influence the sustainability and environment of low-cost low-rise residential buildings. Each subchapter has a few recommendations to improve the performance of low-cost low-rise residential. Each of the factors mentioned is related to social, economic and environmental sustainability. In addition, the study discovered a strong connection between low-cost low-rise residential performance and user satisfaction.