bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conformational Change of Syntaxin-3b in Regulating SNARE Complex Assembly in the Ribbon Synapses
Authors: Gething Claire , Ferrar Joshua , Misra Bishal , Howells Giovanni , Choi Ucheor B. 
Published: September 2021

AbstractNeurotransmitter release of synaptic vesicles relies on the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, consisting of syntaxin and SNAP-25 on the plasma membrane and synaptobrevin on the synaptic vesicle. The formation of the SNARE complex progressively zippers towards the membranes, which drives membrane fusion between the plasma membrane and the synaptic vesicle. However, the underlying molecular mechanism of SNARE complex regulation is unclear. In this study, we investigate the syntaxin-3b isoform found in the retinal ribbon synapses using single-molecule fluorescence resonance energy transfer (smFRET) to monitor the conformational changes of syntaxin-3b that modulate the SNARE complex formation. We found that syntaxin-3b is predominantly in a self-inhibiting closed conformation, inefficiently forming the ternary SNARE complex. Conversely, a phosphomimetic mutation (T14E) at the N-terminal region of syntaxin-3b promoted the open conformation, similar to the constitutively open form of syntaxin LE mutant. When syntaxin-3b is bound to Munc18-1, SNARE complex formation is almost completely blocked. Surprisingly, the T14E mutation of syntaxin-3b partially abolishes Munc18-1 regulation, acting as a conformational switch to trigger SNARE complex assembly. Thus, we suggest a model where the conformational change of syntaxin-3b induced by phosphorylation initiates the release of neurotransmitters in the ribbon synapses.
GCN5L1 promotes diastolic dysfunction by inhibiting cardiac pyruvate oxidation
Authors: Thapa Dharendra , Bugga Paramesha , Mushala Bellina A.S. , Manning Janet R. , Stoner Michael W. , McMahon Brenda , Zeng Xuemei , Cantrell Pamela S. , Yates Nathan , Xie Bingxian , Edmunds Lia R. , Jurczak Michael J. , Scott Iain 
Published: September 2021

ABSTRACTLeft ventricular diastolic dysfunction is a structural and functional condition that precedes the development of heart failure with preserved ejection fraction (HFpEF). The etiology of diastolic dysfunction includes alterations in fuel substrate metabolism that negatively impact cardiac bioenergetics, and may precipitate the eventual transition to heart failure. To date, the molecular mechanisms that regulate early changes in fuel metabolism leading to diastolic dysfunction remain unclear. In this report, we use a diet-induced obesity model and quantitative acetylproteomics in aged mice to show that inhibitory lysine acetylation of the pyruvate dehydrogenase (PDH) complex promotes energetic deficits and diastolic dysfunction in mouse hearts. Cardiomyocyte-specific deletion of the mitochondrial lysine acetylation regulatory protein GCN5L1 prevented hyperacetylation of the PDH complex subunit PDHA1, allowing aged obese mice to continue using pyruvate as a bioenergetic substrate in the heart. Our findings suggest that changes in mitochondrial protein lysine acetylation represent a key metabolic component of diastolic dysfunction that precedes the development of heart failure.
CardIAP: Calcium images analyzer web application
Authors: Rueda Ana Julia Velez , Smith Agustín García , Gonano Luis Alberto , Fornasari Maria Silvina , Parisi Gustavo , Sommese Leandro Matías 
Published: September 2021

AbstractMotivationIonic calcium (Ca2+) plays the role of the second messenger in eukaryotic cells associated with cellular functions of regulation of the cell cycle, such as transport, motility, gene expression, and metabolism (Permyakov and Kretsinger, 2009). The use of fluorometric techniques in isolated cells, loaded with Ca2+ sensitive fluorescent probes allows the quantitative measurement of dynamic events that occur in living, functioning cells. The Cardiomyocytes Images Analyzer Application (CardIAP) covers the need for tools to analyze and retrieve information from confocal microscopy images, in a systematic, accurate, and fast way.ResultsHere we present the CardIAP web app, an automated method for the identification of spatio-temporal patterns in a calcium fluorescence imaging sequence. Through this tool, users can analyze single or multiple Ca2+ transients from confocal line-scan images and obtain quantitative information on the dynamic response of the stimulated myocyte.Our web application also allows the user the extraction of data on calcium dynamics in downloadable tables and plots, simplifying the calculation of the alternation and discordance indices and their classification. CardIAP could assist in studying the underlying mechanisms of anomalous calcium release phenomena.Availability and implementationCardIAP is an open-source app, entirely developed in Python, which can be freely accessed and used at http://cardiap.herokuapp.com/.
Interaction of hypoxia and nicotine acetylcholine receptor signaling network reveals a novel mechanism for lung adenocarcinoma progression in never-smokers
Authors: Pandey Namita , Chongtham Jonita , Pal Soumyadip , Mohan Anant , Srivastava Tapasya 
Published: September 2021

AbstractHigh incident of lung cancer among never smokers and their disease pathogenesis is an unexplained phenomenon. We have analyzed 1727 lung cancer patient data to understand the impact of smoking on overall survival of lung cancer patients and have observed a difference of only 47 days between smokers and never smokers in adenocarcinoma patients suggesting that the disease is equally fatal in never-smokers irrespective of gender. In this study, we have investigated the possible collaboration between the nAChR and hypoxia signaling pathway to elucidate a mechanism of disease progression in never-smokers. We report a previously unidentified increase in both acetylcholine and nAChR-α7 levels in non small cell lung cancer cells in hypoxia. Similar increase in ubiquitously expressed nAChR-α7 transcripts was also observed in other cancer lines. A direct binding of HIF-1α with the hypoxia response element (HRE) present at -48 position preceding the transcriptional start site in nAChR-α7 promoter region was established. Significantly, the increased acetylcholine levels in hypoxia drove a feedback loop via modulation of PI3K/AKT pathway to stabilize HIF-1α in hypoxia. Further, Bungarotoxin, an antagonist of nAChR-α7 significantly reversed hypoxia mediated metastasis and induction of HIF-1α in these cells. Our study gives a plausible explanation for the equally worse prognosis of lung adenocarcinoma in never-smokers wherein the nAChR signaling is enhanced in hypoxia by acetylcholine, in the absence of nicotine.
SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes
Authors: Pawlica Paulina , Yario Therese A. , White Sylvia , Wang Jianhui , Moss Walter N. , Hui Pei , Vinetz Joseph M. , Steitz Joan A. 
Published: September 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), continues to be a pressing health concern. In this study, we investigated the impact of SARS-CoV-2 infection on host microRNA (miRNA) populations in three human lung-derived cell lines, as well as in nasopharyngeal swabs from SARS-CoV-2 infected individuals. We did not detect any major and consistent differences in host miRNA levels after SARS-CoV-2 infection. However, we unexpectedly discovered a viral miRNA-like small RNA, named vmiR-5p (for viral miRNA), derived from the SARS-CoV-2 ORF7a transcript. Its abundance ranges from low to moderate as compared to host miRNAs. vmiR-5p functionally associates with Argonaute proteins — core components of the RNA interference pathway — leading to downregulation of host transcripts. One such host messenger RNA encodes Basic Leucine Zipper ATF-Like Transcription Factor 2 (BATF2), which is linked to interferon signaling. We demonstrate that vmiR-5p production relies on cellular machinery, yet is independent of Drosha protein, and is enhanced by the presence of a strong and evolutionarily conserved hairpin formed within the ORF7a sequence.Significance statementWe discovered that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses a small viral non-coding RNA, named vmiR-5p (for viral miRNA), derived from the ORF7a transcript. vmiR-5p associates with the cellular RNA interference machinery to regulate host transcripts likely via target silencing. The production of vmiR-5p relies on cellular machinery and the formation of a strong hairpin within ORF7a sequences. This newly-described vmiR-5p may contribute to SARS-CoV-2 pathogenesis and could become a target for therapeutic intervention.
Consumption behavior and purchase intention of cultured meat in the capital of the “state of barbecue,” Brazil
Authors: Munz Fernandes Alice , Teixeira Costa Lucas , de Souza Teixeira Odilene , dos Santos Francisca Viviane , Palma Revillion Jean Philippe , Leal de Souza Ângela Rozane 
Published: September 2021

PurposeThe purpose of this paper is to analyze the attitudes of meat consumers in Rio Grande do Sul, Brazil, concerning cultured meat. This State is characterized by its strong cultural identity and social practices, barbecue being its typical dish.Design/methodology/approachThe authors applied a cross-sectional survey with meat consumers residing in Porto Alegre/RS, the sample of which, composed of 538 individuals, expressed the population heterogeneity. The data were analyzed using the Pearson chi-square, Cramer'sV, and correspondence analysis.FindingsThe results demonstrate that although six of ten people were willing to try cultured meat, only four of them responded positively to the willingness to consume it over conventional meat. Young individuals demonstrated a favorable attitude towards the product, expressing a greater propensity both to try it and to include it in the diet regularly. However, the rejection of cultured meat gradually intensified after 40 years old. The previous knowledge and familiarity with the investigated subject are not predictive of the intention of experimentation so that almost two-thirds of the individuals who did not know the product were positively willing to try it.Originality/valueDespite the recent intensification of studies about consumer behavior towards cultured meat, its analysis in a context in which meat historically plays a fundamental role in socioeconomic development is still little explored. The originality of our research is circumscribed by the understanding of the behavior of meat consumers, members of a culture where it plays a central role.
Amma Unavagam: mitigating food insecurity through state sponsored food subsidisation programme
Authors: Chandra Deepti 
Published: September 2021

Learning outcomes
The following are the learning objectives of the case study: to address the problem of urban food insecurity. To facilitate the generation of more employment opportunities and women empowerment through self-help groups (SHGs). To understand the transition from the founder to new leadership provided by Ms J Jayalalithaa. To understand consumer perception and preferences for “Amma canteens”. To appreciate how the case study has added to the historical role of soup kitchens. To address the challenges faced by the government on the sustainability and viability of “Amma canteens” post the death of its founder Ms Jayalalithaa.

Case overview/synopsis
“Amma Unavagam” is a food subsidisation programme operated by the State Government of Tamil Nadu in India. Under the scheme, municipal corporations of the state are required to run canteens that serve subsidised food. The canteens were first launched by the then Chief Minister of the state Ms Jayalalithaa, who was widely acknowledged as “Amma”. These low-cost canteens will be announced as part of government schemes aimed to support economically disadvantaged sections of society. The scheme had been able to generate employment for thousands of women. However, the success of the scheme lies in the low prices and the cooperative management of all the outlets by the SHGs. The SHGs have been able to run the canteens based on self-governing norms, mutual reciprocity and shared responsibilities. This case study evaluates the role of state-sponsored mechanisms to ensure food security, alleviate food inflation and empower more women in the workforce. Yet, several concerns continue to remain unaddressed. Considering the huge amount of subsidy provided by the state government, the sustainability and economic viability of the scheme are uncertain.

Complexity academic level
This case study can be used for management students studying the basics of management such as teamwork, motivation, leadership and good governance. They may also study government policies and community intervention programmes for the benefit of society. The present case study will help the students to analyse the concept of women empowerment and social inclusion. The students, before discussing the case, may study and read the socio-economic theory of “community engagement and participation”, the “self-help model” and the related “theory of reasoned action/planned behaviour”.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 6: Human resource management.
The sustainability quotient: a trader’s trade-offs
Authors: Goel Meghna 
Published: September 2021

Learning outcomes
The learning outcomes of this case will help the participants to assess values, motivations and interpersonal relations that exist and evolve in a family firm; analyze individual-level strategies in absence of business growth strategy and succession plan; expose trade-offs associated with natural inheritance or merit-based succession; reveal alternate strategies of coping with conflicts in multi-generation multi-family firms.

Case overview/synopsis
This case focuses on leadership, succession and conflicts at Dalal Group, a 50 years old textile yarn trading family-run business. The trading business has 10 members across three generations working in it. The business is making profits but the growth of the business is not synchronous to the number of family members working in it. As revenues are stable and buyers’ network is not growing, an internal tussle has begun among the members to preserve business resources available to them. The founder, who is also the Managing Director of the Group, is about to retire in a couple of years but there is no clear successor to his position. In the absence of a business growth plan and uncertainty about the next leader, members are clueless about their own future and that is affecting their interpersonal relations at work. This has triggered the need for decision and action by the founder, failing which the business might disintegrate. The case author has used personal interview methods and secondary sources like annual reports and manuals of the company to collect data and information.

Complexity academic level
Senior Undergraduates, MBA (Entrepreneurship and Family Business), MBA.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 6: Human resource management.
Self-disclosure of social media users in Indonesia: the influence of personal and social media factors
Authors: Siahaan Mona Natasha , Handayani Putu Wuri , Azzahro Fatimah 
Published: September 2021

PurposeIn the context of social media (SM) use, self-disclosure (SD) behaviour meets users' social and emotional needs, but it is also accompanied by risks that can harm users. This paper aims to identify the factors that influence users' SD behaviour on SM in Indonesia, using a comparative analysis based on age groups.Design/methodology/approachA survey was conducted on 2,210 respondents who were active SM users in Indonesia. Data were processed and analysed using covariance-based structural equation modelling with AMOS 24.0 software.FindingsResults indicate that, in the overall age group data, factors such as use of information (UI), trust, privacy control (PC), interactivity, perceived benefits (PB) and perceived risks (PR) influence users' SD behaviour. This research also found differences in the characteristics of SD behaviour between age groups.Originality/valueFindings from this study can help SM service providers to evaluate the credibility and reliability of their platforms to encourage user retention.
When the Chinese guy becomes the female IT specialist Liu – a conceptualization of reputational shifts in international assignments
Authors: Bernhard Theresa , Holtbrügge Dirk 
Published: September 2021

PurposeInternational assignments rely on interactions between host country nationals (HCNs) and an international assignee (IA). These interactions are significantly determined by the reputation that the IA holds among HCNs. However, reputation has only scarcely been addressed in extant mobility research, and there is a lack of understanding about how the reputation of an IA shifts among HCNs during the course of an assignment. The purpose of this paper is to understand the development of an individual's reputation as well as the interactions between an IA and HCNs in the context of international assignments.Design/methodology/approachThis is a conceptual paper that builds upon the central idea in extant research of individual reputation as a social construction and draws on sensemaking theory to develop its conceptual model.FindingsAs extant research argues for both a temporal and dynamic dimension of reputation, the authors introduce time and reputational richness as central model elements. Furthermore, the conceptual model proposes reputational events as the principal triggers for reputational shifts. Reputational events reveal quantitatively and qualitatively new informational cues about the IA to HCNs, who then use these cues to incrementally construct the IA's reputation in sensemaking processes. In addition, contextual factors of reputational shifts, namely accelerators and amplifiers, are discussed. The authors argue that these contextual factors may affect both the timing and the strength of reputational shifts.Originality/valueThe study introduces a novel conceptual model and contributes to the understanding of individual reputation development as well as the interactions between an IA and HCNs in international assignments.
Outcomes of assistance dog placement in the home for individuals with autism spectrum disorder and their families: A pilot study
Authors: Leung Joyce Yan‐Lok , Mackenzie Lynette , Dickson Claire 
Published: September 2021

AbstractIntroductionEvidence indicates that assistance dogs placed in the home are effective in supporting individuals with Autism Spectrum Disorder (ASD) by increasing social and community participation and promoting quality of life. This study aimed to examine the outcomes of assistance dog placement on quality of life, independence, and participation of families including individuals with ASD placed with an assistance dog compared to families on the waiting list for an autism assistance dog and to evaluate the feasibility of the design for future studies.MethodsA cross‐sectional comparative study was conducted. The Adaptive Behaviour Analysis System, Social Responsiveness Scale, Autism Treatment Evaluation Checklist, Canadian Occupational Performance Measure, and Autism Family Experience Questionnaire were used to evaluate adaptive skills, behaviour, social difficulties, daily functioning, and family quality of life.ResultsSix families who had an autism assistance dog placed with them, and 12 families who were on the waiting list were recruited using purposeful sampling. The pilot data found no significant differences between the two groups. However, trends were observed which suggested that assistance dogs can increase desired social behaviours, decrease ASD severity, and improve family wellbeing. For families with an assistance dog, more positive outcomes were observed for families who were partnered with an assistance dog for longer. Parents (and sometimes individuals with ASD) were able to complete and return the outcome measures via mail to collect the outcome data for the study.ConclusionThese study findings add to the developing evidence about the use of assistance dogs with this population. A larger sample size may have allowed for significant associations to be detected. The methods used were feasible to be applied in a larger study. These results may assist health professionals advocate for funding for assistance dog placement to individuals with ASD and their families.
Bevacizumab and gastrointestinal perforations: a review from the FDA Adverse Event Reporting System (FAERS) database
Authors: Wichelmann Thomas A. , Abdulmujeeb Sufyan , Ehrenpreis Eli D. 
Published: September 2021

SummaryBackgroundBevacizumab is used in the treatment of advanced malignancies and has a “black box” warning for gastrointestinal perforations. Despite this known side effect, there are no large descriptive series of patients who experience bevacizumab‐induced gastrointestinal perforations.AimTo review and describe post‐market cases of bevacizumab‐induced gastrointestinal perforation reported by healthcare professionals to the United States Food and Drug Association Adverse Event Reporting System (FAERS) database.MethodsIn total, 74 025 cases of bevacizumab‐induced adverse drug reaction were reported to FAERS from January 1 2004 to July 6 2021. We identified 2874 cases of bevacizumab‐induced gastrointestinal perforation. A total of 1375 cases were determined to contain complete patient demographic data after the removal of duplicates and were reviewed. Subgroup analysis was completed on gastro‐oesophageal perforations given the lack of prior data.ResultsThe average patient age was 61.9 ± 11.4 years. A total of 698 cases included descriptive locations of perforations with most occurring in the large intestine (385 cases, 55.2% of specifically described cases). Colorectal cancer was the most common indication for bevacizumab (691 cases, 50.3%) followed by ovarian cancer (197 cases, 14.3%) and non‐small cell lung cancer (182 cases, 13.2%). Death was reported in 554 patients (40.3% of cases). Sixty‐two cases of gastro‐oesophageal perforation were identified.ConclusionsThis is the largest collective descriptive study of bevacizumab‐induced gastrointestinal perforations, and sheds light on this often fatal complication. We additionally identified and described a rare subgroup of patients experiencing bevacizumab‐induced gastro‐oesophageal perforation not previously described.
Is social polarization bad for the planet? A theoretical inquiry
Authors: Verchere Alban 
Published: September 2021

AbstractThe last four decades have been characterized by growing concerns on two key matters: the “environmental question,” arising out of the manifest and accelerating injury to the planet caused by human activity, and the “social question,” concerning the growth of social polarization and the surge in inequality. This paper addresses the possible ecological impact of social polarization by employing an analytical framework where social classes are differentiated not only by their means but also by their tastes and preferences. We see that the ecological impact of social polarization (or, equivalently, of the decline of the middle class) remains unclear even when, as here, the middle class exhibits more proecological tastes than the other classes, so that we might have imagined that its decline would inevitably impair the planet. We then establish the exact critical threshold for the proportion of the middle class above which their accessing the upper class would harm the planet and discuss its sensitivity to key parameters such as, for instance, the level of inequality. Finally, we tackle the topic of public action to limit the risk that social polarization should lead to greater ecological injury.