bluuebunny/crossref_metadata_2025_split huggingface dataset:
LoxCode in vivo barcoding resolves epiblast clonal fate to fetal organs
Authors: Weber Tom S. , Biben Christine , Miles Denise C. , Glaser Stefan , Tomei Sara , Lin Michael , Kueh Andrew , Pal Martin , Zhang Stephen , Tam Patrick P. L. , Taoudi Samir , Naik Shalin H. 
Published: January 2023

AbstractMuch remains to be learned about the clonal fate of mammalian epiblast cellsin vivo. Here we develop a high diversity, high throughput, Cre recombinase-driven DNA LoxCode barcoding technology forin vivoclonal lineage tracing. E5.5 pre-gastrulation embryos were barcodedin uteroand epiblast clones later assessed for their contribution to a wide range of tissues and cell types in the E12.5 organogenesis-stage embryo. While a few epiblast clones contributed broadly to most tissues and cell types of the three germ layers, many clones were lineage biased towards either blood, ectoderm lineages, mesenchymal tissues or limbs. In addition to lineage bias, most epiblast clones were differentially fated for tissue types or descendants in tissues compartments across the body axes. Using a stochastic agent-based model of embryogenesis and LoxCode barcoding, we inferred and experimentally validated predicted cell fate biases as well as clonal compositions across tissues that are consistent with events of lineage segregation and shared trajectory of lineage differentiation. Our study has demonstrated the power of LoxCode barcoding in investigating multi-modal clonal fate at high throughput, thus enabling an in-depth interrogation of the clonal contribution of E5.5 epiblast cells to fetal tissues, organs and body parts.
Ethyl Maltol Disrupts Iron Homeostasis in SH-SY5Y Neuroblastoma Cell Line
Authors: Sun Yuchen , Bressler Joseph 
Published: January 2023

AbstractEthyl Maltol (EM) is a commonly used flavoring compound and has been reported to bind iron and facilitate iron transport. Because EM is highly lipophilic, the potential that it disrupts intracellular iron homeostasis was investigated. EM increased the labile iron pool in SH-SY5Y cells and increased iron-responsive protein activity using a reporter assay in the HEK293 cells. EM induced the expression of transferrin receptor 1 mRNA and decreased expression of ferritin light chain protein in SH-SY5Y cells. Expression of the iron-responsive protein amyloid precursor protein attenuated the effects of EM on these iron-responsive genes. EM treatment decreased cell viability and increased DNA damage. EM also induced the phosphorylation of p53 and the expression of the p53 regulated genes, p21 and 14-3-3σ. The expression of APP attenuated the effects of EM on viability, DNA damage, and the p53 response. Overall, we suggest that EM decreases cell viability through a mechanism involving the p53 pathway. The attenuated responses observed in cells expressing APP suggests that the effects of EM are due to disrupting iron homeostasis.
Systematic assessment of the contribution of structural variants to inherited retinal diseases
Authors: Wen Shu , Wang Meng , Qian Xinye , Li Yumei , Wang Keqing , Choi Jongsu , Pennesi Mark E. , Yang Paul , Marra Molly , Koenekoop Robert K. , Lopez Irma , Matynia Anna , Gorin Michael , Sui Ruifang , Yao Fengxia , Goetz Kerry , Porto Fernanda Belga Ottoni , Chen Rui 
Published: January 2023

ABSTRACTDespite increasing success in determining genetic diagnosis for patients with inherited retinal diseases (IRDs), mutations in about 30% of the IRD cases remain unclear or unsettled after targeted gene panel or whole exome sequencing. In this study, we aimed to investigate the contributions of structural variants (SVs) to settling the molecular diagnosis of IRD with whole-genome sequencing (WGS). A cohort of 755 IRD patients whose pathogenic mutations remain undefined was subjected to WGS. Four SV calling algorithms including include MANTA, DELLY, LUMPY, and CNVnator were used to detect SVs throughout the genome. All SVs identified by any one of these four algorithms were included for further analysis. AnnotSV was used to annotate these SVs. SVs that overlap with known IRD-associated genes were examined with sequencing coverage, junction reads, and discordant read pairs. PCR followed by Sanger sequencing was used to further confirm the SVs and identify the breakpoints. Segregation of the candidate pathogenic alleles with the disease was performed when possible. In total, sixteen candidate pathogenic SVs were identified in sixteen families, including deletions and inversions, representing 2.1% of patients with previously unsolved IRDs. Autosomal dominant, autosomal recessive, and X-linked inheritance of disease-causing SVs were observed in 12 different genes. Among these, SVs inCLN3, EYS, PRPF31were found in multiple families. Our study suggests that the contribution of SVs detected by short-read WGS is about 0.25% of our IRD patient cohort and is significantly lower than that of single nucleotide changes and small insertions and deletions.
Rare catechol-O-methyltransferase (COMT) missense variants are structurally unstable proteasome targets
Authors: Larsen Fia B. , Cagiada Matteo , Dideriksen Jonas , Stein Amelie , Lindorff-Larsen Kresten , Hartmann-Petersen Rasmus 
Published: January 2023

AbstractCatechol-O-methyltransferase (COMT) is a key enzyme in the metabolism of catecholamines. Substrates of the enzyme include neurotransmitters such as dopamine and epinephrine, and therefore, COMT plays a central role in neurobiology. Since COMT also metabolises catecholamine drugs such as L-DOPA, variation in COMT activity could affect pharmacokinetics and drug availability. Certain COMT missense variants have been shown to display decreased enzymatic activity. Additionally, studies have shown that such missense variants may lead to loss-of-function induced by impaired structural stability, which results in activation of the protein quality control system and degradation by the ubiquitin-proteasome system. Here, we demonstrate that two rare missense variants of COMT are ubiquitylated and targeted for proteasomal degradation as a result of structural destabilisation and misfolding. This results in strongly reduced intracellular steady-state levels of the enzyme, which for the L135P variant is rescued upon binding to the COMT inhibitors entacapone and tolcapone. Our results reveal that the degradation is independent of the COMT isoform, as both soluble (S-COMT) and ER membrane-bound (MB-COMT) variants are degraded.In silicostructural stability predictions identify regions within the protein that are critical for stability overlapping with evolutionarily conserved residues, pointing towards other variants that are likely destabilised and degraded.
Generation of nanobodies acting as silent and positive allosteric modulators of the α7 nicotinic acetylcholine receptor
Authors: Li Qimeng , Nemecz Ákos , Aymé Gabriel , de la Bâtie Gabrielle Dejean , Prevost Marie S , Pons Stéphanie , Barilone Nathalie , Baachaoui Rayen , Maskos Uwe , Lafaye Pierre , Corringer Pierre-Jean 
Published: January 2023

AbstractThe α7 nicotinic acetylcholine receptor (nAChR), a potential drug target for treating cognitive disorders, mediates communication between neuronal and non-neuronal cells. Although many competitive antagonists, agonists, and partial-agonists have been found and synthesized, they have not led to effective therapeutic treatments. In this context, small molecules acting as positive allosteric modulators binding outside the orthosteric, acetylcholine, site have attracted considerable interest. Two single-domain antibody fragments, C4 and E3, against the extracellular domain of the human α7-nAChR were generated through alpaca immunization with cells expressing a human α7-nAChR/mouse 5-HT3A chimera, and are herein described. They bind to the α7-nAChR but not to the other major nAChR subtypes, α4β2 and α3β4. E3 acts as a slowly associating positive allosteric modulator, strongly potentiating the acetylcholine-elicited currents, while not precluding the desensitization of the receptor. An E3-E3 bivalent construct shows similar potentiating properties but displays very slow dissociation kinetics conferring quasi-irreversible properties. Whereas, C4 does not alter the receptor function, but fully inhibits the E3-evoked potentiation, showing it is a silent allosteric modulator competing with E3 binding. Both nanobodies do not compete with α-bungarotoxin, localizing at an allosteric extracellular binding site away from the orthosteric site. The functional differences of each nanobody, as well as the alteration of functional properties through nanobody modifications indicate the importance of this extracellular site. The nanobodies will be useful for pharmacological and structural investigations; moreover, they, along with the extracellular site, have a direct potential for clinical applications.
NEK1-Mediated Phosphorylation of YAP1 is key to Prostate Cancer Progression
Authors: Ghosh Ishita , Khalil Imtiaz Md , Mirza Rusella , King Judy , Olatunde Damilola , De Benedetti Arrigo 
Published: January 2023

AbstractUnderstanding how Androgen-dependent PCa cells progress to independence and modify accordingly their transcriptional repertoire is the key to preventing mCRPC progression. We recently identified a novel axis of the Hippo pathway characterized by the sequential kinase cascade induced by androgen deprivation: AR−>TLK1B>NEK1>pYAP1-Y407 leading to CRPC adaptation. Phosphorylation of YAP-Y407 increases upon ADT or induction of DNA damage, correlated with the known increase in NEK1 expression/activity, and this is suppressed in the Y407F mutant. Dominant expression of YAP1-Y407F in Hek293 cells reprograms the YAP1-mediated transcriptome to reduced TEAD- and P73-regulated gene expression and mediates sensitivity to MMC. NEK1 haploinsufficient TRAMP mice display reduced YAP1 expression and if castrated fail to progress to overt prostate carcinomas, even while displaying reduced E-CAD expression in hyperplastic ductules. YAP1 overexpression, but not the Y407F mutant, transforms LNCaP cells to androgen independent growth and a mesenchymal morphology. Immunohistochemical examination of Prostate Cancer biopsies revealed that pYAP1-Y407 nuclear signal is low in samples of low-grade cancer but elevated in high GS specimens. We also found that J54, pharmacological inhibitor of the TLK1>NEK1>YAP1 nexus, leading to degradation of YAP1 can suppress the transcriptional reprogramming of LNCaP cells to Androgen-Independent growth and EMT progression even when YAP1-WT is overexpressed.
Enhancing students’ understanding and performance in a distance-learning setting: evidence from an audit simulation at a GCC university
Authors: Elsayed Nader , Ismael Hazem Ramadan , Saadullah Shahriar M. 
Published: January 2023

Purpose
Drawing on experiential learning theory (ELT), this study aims to examine students’ performance and perceptions after performing an experiential learning activity (ELA) by completing a mini-audit simulation (AS) on the purchase and cash disbursement processes in a distance-learning environment at a Gulf Cooperation Council (GCC) university.

Design/methodology/approach
Adopting a mixed-methods approach, we collected quantitative and qualitative data from 176 students using the grade centre on Blackboard and their responses to a semi-structured questionnaire.

Findings
The pre-and post-simulation tests indicate significant improvement in students’ understanding and performance after performing the mini-AS. The students’ responses also provide robust evidence of student engagement, active participation and positive recognition of the AS’s value.

Practical implications
This study has several implications: for the accounting education literature, how AS strengthens in-depth learning through the lens of ELT; for professional accounting bodies, informing the need to maximise the awareness and benefits of adopting simulations in accounting education and examination; and for educators, considering simulations in their ELAs to enhance student learning.

Originality/value
This study introduces a new authentic mini-AS instrument that can be adapted to a distance-learning setting, adds to the very limited studies in AS using ELT, uses a mixed-methods approach and explores students who learn in an Arabic-speaking country.
Does corporate governance quality improve credit ratings of financial institutions? Evidence from ownership and board structure
Authors: Mili Mehdi , Alaali Yusuf 
Published: January 2023

PurposeThe purpose of this paper is to examine to which extent ownership and board structure improve financial institutions’ credit ratings.Design/methodology/approachOrdered Probit regression models were used to examine the association between corporate governance attributes and banks’ credit ratings. The sample consists of 97 publicly traded financial institutions on Gulf Cooperation Council (GCC) stock exchange markets and cover the period 2010–2019. All GCC countries were considered in this study which are United Arab Emirates, Saudi Arabia, Bahrain, Oman, Kuwait and Qatar.FindingsThe results show that banks’ credit ratings are positively associated with the size of the board of directors and with the number of female directors serving in the board of directors. And it is negatively associated with the frequency of board meetings. Furthermore, this study finds evidence that nonbank financial institutions’ credit ratings are positively associated with CEO duality and with frequency of board meetings. Also, this study shows that their credit ratings are negatively associated with the ownership percentage held by the major five shareholders and with the number of board members serving in the board of directors.Originality/valueUnlike previous research, this study focuses on the effect of the role of two different corporate governance dimensions, namely, ownership and board structure on the rating of financial institutions. This paper contributes to the extant literature in various ways. It bridges the gap of this topic in the GCC region. And, unlike previous research, this study focused on the financial sector and divided the sample into banks and other financial institutions to examine both subsamples separately. Also, this study introduced new ownership and board structure variables for the purpose of investigating the impact of corporate governance on financial institutions’ credit ratings such as the presence of women in the board of directors.
The influence of knowledge creation process on customer relations management: evidence from Palestinian commercial banks
Authors: Abusharbeh Mohammed 
Published: January 2023

PurposeThe purpose of this study is to examine the influence of knowledge creation (KC) process on customer relations management (CRM) in Palestinian commercial banks, taking into consideration which factors of KC process support the CRM system.Design/methodology/approachThe study uses a quantitative research design wherein questionnaires have been used to collect data from 345 respondents in the Palestinian banking sector. Research hypotheses have been tested using multiple regression analysis.FindingsThe findings unveil that socialisation and combination processes have a positive impact on CRM. In contrast, internalisation process negatively affects CRM system, but outsourcing knowledge does not significantly affect CRM.Research limitations/implicationsPast studies empirically validated the success of CRM adaptation in the context of different industries. This study provides a new conceptual model which validates the influence of KC on CRM in the banking sector. It also affirms the integral role of KC in supporting CRM from an emerging country perspective like Palestine.Practical implicationsThis study offers new insights into creating of knowledge by employees in supporting CRM. It will encourage future scholars to further explore the key dimensions of the KC process for a more detailed investigation at a workplace. This study suggests that banks’ directors and employees should behave in a social manner to support relationship with customers. This study also suggests facilitating knowledge from different resources in innovative ways, through encouraging creative thinking from experiences, using technology in sharing knowledge, focussing on appropriate training to resolve customers' problems and disseminating new knowledge among employees.Originality/valueThis study expands the body of knowledge on KC process in supporting CRM from an emerging country perspective. This study validates the influence of KC on CRM in the Palestinian banking sector. This sheds light on the integration of these two concepts.
Bringing clarity to the leadership of teaching and learning in higher education: a systematic review
Authors: Kinnunen Päivi , Ripatti-Torniainen Leena , Mickwitz Åsa , Haarala-Muhonen Anne 
Published: January 2023

PurposeThe study aims to investigate the state of higher education (HE) leadership research after the intensified focus on teaching and learning (TL) in academia.Design/methodology/approachThe authors clarify the use of key concepts in English-medium empirical journal articles published between 2017 and 2021 by analysing 64 publications through qualitative content analysis.FindingsThe analysed papers on leadership of TL in HE activate a number of concepts, the commonest concepts being academic leadership, distributed leadership, educational leadership, transformational leadership, leadership and transformative leadership. Even if the papers highlight partly overlapping aspects of leadership, the study finds a rationale for the use of several concepts in the HE context. Contrary to the expectation raised in earlier scholarship, no holistic framework evolves from within the recent research to reveal the contribution that leadership of TL makes to leadership in HE generally.Research limitations/implicationsLimitations: Nearly 40 per cent of the analysed articles are from the United States of America (USA), United Kingdom (UK), Australia and Canada, which leaves large areas of the world aside. Implications: The found geographical incoherence might be remediated and the research of leadership of TL in HE generally led forward by widening the cultural and situational diversity in the field.Originality/valueThis research contributes to an enhanced understanding of the field of leadership in TL in HE in that it frames the concepts used in recent research and makes the differences, similarities and rationale between concepts visible.
A systematic literature review of money mule: its roles, recruitment and awareness
Authors: Abdul Rani Mohd Irwan , Syed Mustapha Nazri Sharifah Nazatul Faiza , Zolkaflil Salwa 
Published: January 2023

Purpose
This paper aims to provide a systematic literature review (SLR) on contemporary cardinal money mule issues.

Design/methodology/approach
This paper reviews the most common money mule themes in perpetrating financial crime activities, especially its roles, recruitment and awareness. A systematic review protocol called preferred reporting items for systematic review and meta-analysis protocols is adopted for this study.

Findings
Money mules are used by organized criminal groups (OCG) or fraudster to launder illicit funds from outrageous criminal activities. They allow their accounts to be used for money laundering by OCG. The attacker, OCG or fraudsters would layer the stolen funds using money mule accounts. These money mules are recruited using various approaches, oftentimes deceived by opulent lifestyles to captivate the interest of potential money mules.

Originality/value
This paper presents money mule awareness needed by accountant, bank employees and the society. It is an unprecedented SLR on money mule. This paper will be beneficial for future money mule researchers, enforcement agencies and practitioners in banking industry.
Signaling norm salience through perceived peer counterfeit consumption
Authors: Khan Sameeullah , Fazili Asif Iqbal , Bashir Irfan 
Published: January 2023

Purpose
This paper aims to theorize that millennials' counterfeit buying behavior is partly driven by perceived peer counterfeit consumption – the perception that counterfeit luxury consumption is a norm within members of their own generation.

Design/methodology/approach
The research is based on two survey-based studies: Study 1 investigates the phenomenon on young millennials (n = 438) and Gen X (n = 374) using moderation analyses in PROCESS Macro; and Study 2 is based on young millennials (n = 643) and runs a partial least squares structural equation modeling model.

Findings
The findings reveal that perceived counterfeit consumption within own (vs other) generation leads to greater counterfeit purchase intention and this effect is stronger for young millennials (vs Gen X). Counterfeiting values (materialism, counterconformity and morality) strengthen the impact of perceived peer counterfeit consumption on the counterfeit purchase intention of young millennials, thereby establishing counterfeit luxury consumption as a salient norm.

Practical implications
To modify perceptions about peer counterfeiting norms, normative messages must communicate counterfeit avoidance among millennials through social media influencers. Luxury brand managers must focus on the experiential value of luxury and pursue unconventional luxury inspired by a sense of rebelliousness and independence.

Originality/value
This work demonstrates that millennials engage in counterfeit luxury consumption when they perceive it as a salient consumption norm among members of their own generation. It adds a novel construct of perceived counterfeit consumption and demonstrates the role of generation as a normative referent. The article provides a values-based motivational account of conformity to peer counterfeiting norms.