bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ts65Dn synaptic proteome partially recapitulates AD biochemical signature
Authors: Gómez de Salazar Macarena 
Published: April 2023

ABSTRACTDown syndrome (DS), caused by human chromosome 21 trisomy, is one of the most common genetic causes of intellectual disabilities. Moreover, approximately 60-80% of individuals with Down Syndrome develop early onset Alzheimer’s disease symptoms and neuropathology characterized by the deposition of senile plaques and neurofibrillary tangles. Spine loss and synaptic deficits are the main alterations present in both pathologies. The synaptic proteins that are altered in both pathologies have also been studied. However, a proteomic study comparing synaptic fractions from DS and AD patients is lacking. To address this aim, we optimized a biochemical subfractioning method to isolate postsynaptic fractions from the cortex of Ts65Dn Down syndrome murine model and the entorhinal cortex from AD subjects’ samples. These samples were used for further proteomic analysis to observe potential alterations in postsynaptic protein expression and protein-protein interaction networks. This study compared the Ts65Dn animal model and entorhinal cortex of AD subjects and revealed a common altered postsynaptic composition of the adult Ts65Dn mouse cortex and entorhinal cortex of AD subjects. These postsynaptic protein alterations might functionally underlie Ts65Dn-associated and AD-associated dendritic deterioration, microtubule organization, glutamatergic transmission, and phosphorylation alterations. They provide insight into the possible common pathological synaptic mechanisms of both diseases and the earliest stages of AD disease progression. Moreover, our proteomic data suggest potential drug targets for modulating the commonly altered postsynaptic mechanisms in DS and AD.
A machine vision guided robot for fully automated embryonic microinjection
Authors: Alegria Andrew D. , Joshi Amey S. , Mendana Jorge Blanco , Khosla Kanav , Smith Kieran T. , Auch Benjamin , Donovan Margaret , Bischof John , Gohl Daryl M. , Kodandaramaiah Suhasa B. 
Published: April 2023

ABSTRACTMicroinjection is a widely used technique for transgenesis, mutagenesis, cell labeling, cryopreservation, andin vitrofertilization in multiple single and multicellular organisms. Microinjection requires specialized skills acquired for each target organism and involves rate limiting and labor-intensive preparatory steps. Here we constructed a machine vision (MV) guided generalized robot that fully automates the process of microinjection in fruit fly(Drosophila melanogaster)and zebrafish (Danio rerio) embryos. The robot uses machine learning (ML) models trained to detect individual embryos in images of agar plates, and models trained to identify specific anatomical locations within each embryo in 3D space using dual view microscopes. The robot uses this information to serially perform microinjection in each detected embryo without any human intervention. We constructed and used three such robots to automatically microinject tens of thousands of Drosophila and zebrafish embryos. We systematically optimized robotic microinjection for each species and validated the use of the robot by performing routine transgenesis with proficiency comparable to highly skilled human practitioners while achieving up to 4x increases in microinjection throughput in Drosophila. The automated microinjection robot was utilized to microinject pools of over 20,000 uniquely barcoded plasmids into 1,713 embryos in two days to rapidly generate more than 400 unique transgenic Drosophila lines. This high throughput microinjection experiment enabled a novel measurement of the number of independent germline integration events per successfully injected embryo. Finally, we showed that robotic microinjection of cryoprotective agents in zebrafish embryos significantly improves vitrification rates and survival of cryopreserved embryos post-thaw as compared to manual microinjection, opening the tantalizing possibility of large-scale cryobanking of aquatic species at an industrial scale. We anticipate that this versatile automated microinjection system can be applied to carry out microinjection for genome-wide manipulation and cryopreservation at scale in a wide range of other organisms.
Superior Efficacy of Combination Antibiotic Therapy versus Monotherapy in a Mouse Model of Lyme Disease
Authors: Alruwaili Yasir , Jacobs Mary B. , Hasenkampf Nicole R. , Tardo Amanda C. , McDaniel Celine E. , Embers Monica E. 
Published: April 2023

AbstractLyme disease (LD) results from the most prevalent tick-borne infection in North America, with over 476,000 estimated cases annually. The disease is caused byBorrelia burgdorferi (Bb)which transmits through the bite of Ixodid ticks. Most cases treated soon after infection are resolved by a short course of oral antibiotics. However, 10-20% of patients experience chronic symptoms because of delayed or incomplete treatment, a condition called Post-Treatment Lyme Disease (PTLD). SomeBbpersists in PTLD patients after the initial course of antibiotics and an effective treatment to eradicate the persistentBbis needed. Other organisms that cause persistent infections, such asM. tuberculosis, are cleared using a combination of therapies rather than monotherapy. A group of Food and Drug Administration (FDA)-approved drugs efficacious againstBbwere used in monotherapy or in combination in mice infected withBb. Different methods of detection were used to assess the efficacy of the treatments in the infected mice including culture, xenodiagnosis, and molecular techniques. None of the monotherapies eradicated persistentBb. However, 4 dual combinations (doxycycline + ceftriaxone, dapsone + rifampicin, dapsone + clofazimine, doxycycline + cefotaxime) and 3 triple combinations (doxycycline + ceftriaxone+ carbomycin, doxycycline + cefotaxime+ loratadine, dapsone+ rifampicin+ clofazimine) eradicated persistentBbinfections. These results suggest that combination therapy should be investigated in preclinical studies for treating human Lyme disease.
Large Data on the Small Brain: Population-wide Cerebellar Growth Models of Children and Adolescents
Authors: Gaiser Carolin , van der Vliet Rick , de Boer Augustijn A. A. , Donchin Opher , Berthet Pierre , Devenyi Gabriel A. , Chakravarty M. Mallar , Diedrichsen Jörn , Marquand Andre F. , Frens Maarten A. , Muetzel Ryan L. 
Published: April 2023

AbstractIn the past, the cerebellum has been best known for its crucial role in motor function. However, increasingly more findings highlight the importance of cerebellar contributions in cognitive functions and neurodevelopment. Using large scale, population-wide neuroimaging data, we describe and provide detailed, openly available models of cerebellar development in childhood and adolescence, an important time period for brain development and onset of neuropsychiatric disorders. Next to a traditionally used anatomical parcellation of the cerebellum, we generated growth models based on a recently proposed functional parcellation. In both, we find an anterior-posterior growth gradient mirroring the age-related improvements of underlying behavior and function, which is analogous to cerebral maturation patterns and offers new evidence for directly related cerebello-cortical developmental trajectories. Finally, we illustrate how the current approach can be used to detect cerebellar abnormalities in clinical samples.
Functional archaic DNA regulates molecular variation and is associated with disease risk across global populations
Authors: Kang Jianning , Ramgolam Aimee S , Vot Louise Le , Young Robert S. 
Published: April 2023

AbstractThe human genome contains many remnants of its evolutionary history, including a large number of evolutionarily volatile loci which have been introduced since our divergence from primates. One particularly intriguing source of novel DNA sequences is introgression events with archaic species which co-existed with modern humans. Both Neanderthals, who were common in Europe, and Denisovans, who have been observed only in Asia, have contributed genetic variants to the modern human genome but the functional consequences of these introgressed variants have yet to be investigated systematically. In this work, we show that Neanderthal and Denisovan DNA is most enriched for genetic variants which regulate gene expression in Europe and East Asia respectively, i.e. the populations in which the introgression event(s) most contributed to contemporary genetic variation. Neanderthal eQTLs, in particular, frequently upregulate gene expression. Archaic eQTLs from these two species regulate target genes with similar molecular functions which are distinct in each contemporary population, with the only common enrichment being for Neanderthal eQTLs to regulate taste receptor genes in both Europe and East Asia. We observed a correlated pattern of enrichment and depletion of medical phenotypes across Neanderthal and Denisovan eQTLs, including a shared enrichment for CNVs associated with developmental delay. Our results demonstrate the role of functional archaic DNA in regulating molecular phenotypes and disease risk across global populations and confirm the relevance of recently acquired DNA to contemporary human genetic variation.Author SummaryModern humans co-existed and interbred with two archaic human species (Neanderthals and Denisovans). The results of these events can still be detected as introgressed, archaic DNA sequences within the modern human genome. Here, we surveyed the contribution of functional archaic DNA across European and Asian populations by assessing their contribution to genetic variants which regulate gene expression in these two populations. We found that both species make a disproportionate functional contribution to the population with which they shared the most overlap (i.e. Neanderthals in Europe and Denisovans in East Asia). Although only Neanderthal DNA drives a higher level of gene expression compared to modern genetic variants, the DNA from both archaic species frequently regulates genes involved in many different biological processes and risk of disease, including a shared contribution to developmental delay. These results confirm the relevance of our recent evolutionary past in generating functional variation across global populations and the importance these recently introduced genetic sequences play in regulating current biological variation, such as disease risk.
A farnesyl-dependent structural role for CENP-E in expansion of the fibrous corona
Authors: Wu Jingchao , Raas Maximilian W.D. , Alcaraz Paula Sobrevals , Vos Harmjan R. , Tromer Eelco C. , Snel Berend , Kops Geert J.P.L. 
Published: April 2023

SummaryCorrect chromosome segregation during cell division depends on proper connections between spindle microtubules and kinetochores. During prometaphase, kinetochores are temporarily covered with a dense protein meshwork known as the fibrous corona. Formed by oligomerization of ROD/ZW10/ZWILCH-SPINDLY (RZZ-S) complexes, the fibrous corona promotes spindle assembly, chromosome orientation and spindle checkpoint signaling. The molecular requirements for formation of the fibrous corona are not fully understood. Here we show that the fibrous corona depends on the mitotic kinesin CENP-E, and that poorly expanded fibrous coronas after CENP-E depletion are functionally compromised. This previously unrecognized role for CENP-E does not require its motor activity but instead is driven by farnesyl modification of its C-terminal kinetochore-and microtubule-binding domain. We show that in cells CENP-E interacts with RZZ-S complexes in a farnesyl-dependent manner. CENP-E is recruited to kinetochores following RZZ-S, and - while not required for RZZ-S oligomerization per se - promotes subsequent fibrous corona expansion. Our comparative genomics analyses suggest that the farnesylation motif in CENP-E orthologs emerged alongside the full RZZ-S module in an ancestral lineage close to the fungi-animal split (Obazoa), revealing potential conservation of the mechanisms for fibrous corona formation. Our results show that proper spindle assembly has a potentially conserved non-motor contribution from the kinesin CENP-E through stabilization of the fibrous corona meshwork during its formation.
Tackling stress of project management practitioners in the Australian construction industry: the causes, effects and alleviation
Authors: Jin Xiao-Hua , Senaratne Sepani , Fu Ye , Tijani Bashir 
Published: April 2023

PurposeThe problem of stress is increasingly gaining attention in the construction industry in recent years. This study is aimed at examining the causes, effects and possible alleviation of stress of project management (PM) practitioners so that their stress could be appropriately managed and reduced, which would contribute to improved mental health.Design/methodology/approachPrimary data were collected in an online questionnaire survey via Qualtrics. Questions ranged from PM practitioners’ stressors, stress and performance under stress to stress alleviation tools and techniques. One hundred and five PM practitioners completed the questionnaire. Their responses were compiled and analyzed using descriptive statistics, correlation and regression.FindingsThe results confirmed that the identified stressors tended to increase stress of PM practitioners. All stressors tested in this study were found to have negative impact on the performance of PM practitioners. In particular, the burnout stressors were seen as the key stressors that influence the performance of PM practitioners and have a strong correlation with all the other stressors. It was also found that a number of tools and techniques can reduce the impact of stressors on PM practitioners.Originality/valueThis study has taken a specific focus on stress-related issues of PM practitioners in the construction industry due to their critical role in this project-dominated industry. Using the Job Demand-Resource theory, a holistic examination was not only conducted on stress and stressors but also on alleviation tools and techniques. This study has thus made significant contribution to the ongoing research aimed at finding solutions to mental health-related problems in the project-dominated construction industry, thereby achieving the United Nations’ social sustainability development goals.
Educating the educators to be a driving force in higher education towards sustainable development
Authors: Persson Christel , Einarson Daniel , Melén Maria 
Published: April 2023

Purpose
This study aims to address how a higher education pedagogical course in sustainable development (SD) for university educators affects their teaching efforts in providing sustainability matters for students.

Design/methodology/approach
With the aim of improving that course, a case study approach was used to understand how the educators made use of the course in their teaching practice. Data were collected as written and oral feedback reflections and as semi-structured interviews at course completion.

Findings
Educators clearly express that they understand the concept “about” SD, but there are only vague expressions of a developed teaching repertoire to address education “for” SD in their teaching practice.

Research limitations/implications
When it comes to the purposes of developing sustainability literacy among students, implications from the study furthermore address the needs for further clarifications on both structure and intent on the course presented in this contribution.

Practical implications
The educators as well as their students will be exposed to, and trained in concepts, to prepare them to act in alignment with SD. This, in turn, meets requirements from higher education authorities concerning SD at higher education institutions.

Social implications
A core aim of the covered approach is to support student readiness in SD, and for those to become future agents of positive change.

Originality/value
This study has a focus on presenting how educators change the structures of courses and learning elements to approach SD in their teachings.
AR and VR-based travel: a responsible practice towards sustainable tourism
Authors: Samaddar Kaushik , Mondal Sanjana 
Published: April 2023

Purpose
Drawing on the UTAUT-2 model, the study attempts to accentuate the role of augmented reality (AR) and virtual reality (VR) based tourism products and services in enhancing responsible travel behaviour (RTB). This paper aims to examine the emergence of AR- and VR-based tourism in emerging economies, outlines the issues and contributing factors and discusses possible mitigation measures.

Design/methodology/approach
Following the triangulation method of research, a dual study involving both focus group discussions and questionnaire-based surveys were undertaken. The grounded theory approach was adopted to develop a structural framework followed by an empirical validation process.

Findings
Critical dimensions such as performance anticipation, effort anticipation, referent power, facilitating factors, perceived value and perceived risk were found as antecedents of behavioural intentions (BIs) towards adopting AR- and VR-based tourism products. Moreover, cultural involvement and marketing stimuli emerged as moderating factors driving the BI towards RTB.

Practical implications
This paper outlines key elements that contribute to the adoption of AR- and VR-based tourism products and services in emerging economies, which would enable marketers and practitioners to strategize their tourism offerings.

Originality/value
The study takes a dual perspective of both tourists and tour operators and presents a critical overview of the AR- and VR-based tourism industry, taking an emerging economies’ perspective. The study further attempted both the triangulation method and grounded study approach for establishing a hypothetical framework, which is a unique attempt in itself.
Student motivations for social media use and their effects on academic performance- a meditational approach in emerging market
Authors: Kalam Abul , Goi Chai Lee , Tiong Ying Ying 
Published: April 2023

Purpose
Due to the incredible criticisms by scholars of the excessive use of social media networks, this study aims to explore students’ motivation for social media use (SMU) and its effects on academic performance (AP) in the light of uses and gratification theory.

Design/methodology/approach
Using the simple random and snowball sampling techniques, this study has considered 299 responses and critically analyzed them using structural equation modeling through the AMOS version 24. The mediation analysis has been done to explore the effective use of social media networks.

Findings
The results reveal that video clip watching and nonacademic learning intentions significantly influence SMU and AP. Besides, socialization through friends and family connections has tremendously fostered SMU intention, while it could not benefit AP. This study found an exceptional result that the entertainment intention of the students did not influence SMU but dramatically impacted their AP. Again, SMU has robust effects on enhancing students’ academic achievement. This study also concluded the results of the mediation analysis.

Practical implications
The learners, professionals, higher education policymakers, etc. may benefit from following this study's guidelines for using social media networks.

Social implications
This study may tremendously contribute to changing the mindset of youth from addiction to SMU and improving AP.

Originality/value
The prime novelty of this study is to justify the mediation analysis for SMU to explore whether it can truly influence students’ AP and critically examine the deep insight of certain factors associated with SMU.
Telecommunications regulation, mobile money innovations and financial inclusion
Authors: Asongu Simplice 
Published: April 2023

Purpose
This study aims to assess how corporate telecommunication (telecom) policies follow telecom sector regulation in mobile money innovation for financial inclusion in developing countries.

Design/methodology/approach
Telecom policies are understood in terms of mobile subscriptions, mobile connectivity coverage and mobile connectivity performance, whereas mobile money innovations represent mobile money accounts, the mobile used to send money and the mobile used to receive money. The empirical evidence is based on Tobit regressions.

Findings
Telecom sector regulation positively influences mobile money innovations. From net influences, mobile subscriptions and connectivity policies moderate telecom sector regulation to positively influence mobile money innovations, exclusively within the remit of mobile money accounts because the corresponding net influences on the mobile used to send money and the mobile used to receive money are negative. The interactive influences are consistently negative, and hence, thresholds for complementary policies are provided to maintain the positive influence of telecom sector regulation on mobile money innovations.

Originality/value
This study has complemented the extant literature by assessing how corporate telecommunication policies follow telecommunication sector regulation in mobile money innovations for financial inclusion.
Role of fintech in credit risk management: an analysis of Islamic banks in Indonesia, Malaysia, UAE and Pakistan
Authors: Shah Syed Alamdar Ali , Fianto Bayu Arie , Sheikh Asad Ejaz , Sukmana Raditya , Kayani Umar Nawaz , Bin Ridzuan Abdul Rahim 
Published: April 2023

Purpose
The purpose of this study aims to examine the effect of fintech on pre- and post-financing credit risks faced by the Islamic banks.

Design/methodology/approach
This research uses primary data for fintech awareness and adoption and secondary data of various financial and economic variables from 2009 to 2021. It uses baseline regression to identify moderation of fintech controlling gross domestic products, size, return on assets and leverage. The findings are confirmed using robustness against key variable bias. It also uses a dynamic panel two-stage generalized method of moments for endogeneity.

Findings
The study finds that the fintech awareness and adoption are not the same across all Islamic countries. The Asia Pacific region is far ahead of the other two regions where Indonesia is ahead in terms of fintech awareness and adoption, and Malaysia is ahead in terms of reaping its benefits in credit risk management. Fintech affects prefinancing credit risk significantly more than postfinancing credit risk. Also, the study finds that Islamic banks suffer from the problem of “Adverse selection under Shariah compliance.”

Practical implications
This research invites regulators to introduce fintech in Islamic banks on war footing. Similar studies can be conducted on the role of other risks such as operational and market risks. Fintech will also help in improving the risk profile and stability of Islamic banks against systemic risks and financial crises.

Originality/value
This research has variety of originalities. First, it is the pioneering study that addresses the effect of fintech pre- and post-financing credit risks in Islamic banks. Second, it identifies “Adverse selection under Shariah compliance” for Islamic banks. Third, it helps identify how fintech can be useful in reducing credit risk that will help in reducing capital charge for regulatory capital.