bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hijacking the transcriptional activation potential of the BAF complex via Induced Proximity
Authors: Chia Lionel , Mayhew David , Sherbanee Brenna , Lahr David L. , Taherbhoy Asad M. 
Published: December 2023

AbstractThe BAF (Brg/Brahma-associated factors) complex, also referred to as the mammalian Switch/Sucrose-Nonfermentable (mSWI/SNF) chromatin remodeling complex, plays a pivotal role in epigenetically regulating diverse transcriptional programs. BAF’s chromatin remodeling activity, which enhances accessibility to transcriptional machinery, is critical for gene regulation. Recent studies have demonstrated that redirecting BAF complexes to bivalent promoters can alter the local epigenetic landscape, creating a permissive environment for transcription. As such, we hypothesize that redirecting BAF to “turn on” therapeutically relevant genes offers a potential approach for disease treatment.Using rapamycin as a chemical inducer of proximity (CIP) via CRISPR/Cas9 and FKBP/FRB dimerization, we redirected BAF complexes to the promoter of fetal hemoglobin (HBG), a therapeutic target for beta-globinopathies like sickle cell anemia and beta-thalassemia. This resulted in changes to the local chromatin and epigenetic landscapes, and increasedHBG1expression. Having confirmed BAF’s ability to activate gene expression, we then performed a genome-wide CRISPR activation drop-out screen to identify genes that when activated by BAF, suppress cellular proliferation. In addition to known tumor suppressors, our screen identified a number of genes with the ability to inhibit cell proliferation when activated by BAF. Collectively, our findings highlight the potential for harnessing the BAF’s intrinsic transcriptional activation capabilities for therapeutic purposes and lays the foundation for the potential development of therapeutics that function via induced proximity.
Isolectin B4 (IB4)-conjugated streptavidin for the selective knockdown of proteins in IB4-positive (+) nociceptors
Authors: Bogen O , Araldi D , Sucher A , Kober K , Ohara PT , Levine JD 
Published: December 2023

SummaryIn vivoanalysis of protein function in nociceptor subpopulations using antisense oligonucleotides and short interfering RNAs is limited by their non-selective cellular uptake. To address the need for selective transfection methods, we covalently linked isolectin B4 (IB4) to streptavidin and analyzed whether it could be used to study protein function in IB4(+)-nociceptors. Rats treated intrathecally with IB4-conjugated streptavidin complexed with biotinylated antisense oligonucleotides for protein kinase C epsilon (PKCε) mRNA were found to have: a) less PKCε in dorsal root ganglia (DRG), b) reduced PKCε expression in IB4(+) but not IB4(–) DRG neurons, and c) fewer transcripts of the PKCε gene in the DRG. This knockdown in PKCε expression in IB4(+) DRG neurons is sufficient to reverse hyperalgesic priming, a rodent model of chronic pain that is dependent on PKCε in IB4(+)-nociceptors. These results establish that IB4-streptavidin can be used to study protein function in a defined subpopulation of nociceptive C-fiber afferents.
Human Induced Pluripotent Stem Cell based Hepatic-Modeling of Lipid metabolism associated TM6SF2 E167K variant
Authors: Faccioli Lanuza AP , Sun Yiyue , Motomura Takashi , Liu Zhenghao , Kurihara Takeshi , Hu Zhiping , Cetin Zeliha , Franks Jonathan , Stolz Donna , Ostrowska Alina , Florentino Rodrigo M , Fox Ira J , Soto-Gutierrez Alejandro 
Published: December 2023

AbstractBACKGROUND AND AIMSTM6SF2 rs58542926 (E167K) is associated with an increase in the prevalence of Metabolic Disfunction-Associated Steatotic Liver Disease (MASLD). Despite all the investigation related to the role of this variant in lipid metabolism, conflicting results in mouse studies underscore the importance of creating a human model for understanding the TM6SF2 mechanism. Therefore, the aim of this study is to generate a reliable human in vitro model that mimic the effects of the TM6SF2 E167K mutation and can be used for future mechanism studies.APPROACH AND RESULTSWe performed gene editing on human-induced pluripotent stem cells (iPSC) derived from a healthy individual to obtain the cells carrying the TM6SF2 E167K mutation. After hepatic differentiation, a decrease in TM6SF2 protein expression was observed in the mutated-induced hepatocyte. An increase in intracellular lipid droplets and a decrease in the efflux of cholesterol and ApoB100 were also observed. Transcriptomics analysis showed up-regulation of genes related to the transport, flux, and oxidation of lipids, fatty acids, and cholesterol in TM6SF2 E167K cells. Additionally, signs of cellular stress were observed in the ER and mitochondria.CONCLUSIONSOur findings indicate that induced hepatocytes generated from iPSC carrying the TM6SF2 E167K recapitulate the effects observed in human hepatocytes from individuals with the TM6SF2 mutation. This study characterizes an in vitro model that can be used as a platform to help in the identification of potential clinical targets and therapies and to understand the mechanism by which the TM6SF2 E167K variant leads to vulnerability to MASLD.
Temporal recording of mammalian development and precancer
Authors: Islam Mirazul , Yang Yilin , Simmons Alan J. , Shah Vishal M. , Pavan Musale Krushna , Xu Yanwen , Tasneem Naila , Chen Zhengyi , Trinh Linh T. , Molina Paola , Ramirez-Solano Marisol A. , Sadien Iannish , Dou Jinzhuang , Chen Ken , Magnuson Mark A. , Rathmell Jeffrey C. , Macara Ian G. , Winton Douglas , Liu Qi , Zafar Hamim , Kalhor Reza , Church George M. , Shrubsole Martha J. , Coffey Robert J. , Lau Ken S. 
Published: December 2023

AbstractKey to understanding many biological phenomena is knowing the temporal ordering of cellular events, which often require continuous direct observations [1, 2]. An alternative solution involves the utilization of irreversible genetic changes, such as naturally occurring mutations, to create indelible markers that enables retrospective temporal ordering [3-8]. Using NSC-seq, a newly designed and validated multi-purpose single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonalityin vivo, while incorporating assigned cell state and lineage information. Using this approach, we uncovered precise timing of tissue-specific cell expansion during murine embryonic development and identified new intestinal epithelial progenitor states by their unique genetic histories. NSC-seq analysis of murine adenomas and single-cell multi-omic profiling of human precancers as part of the Human Tumor Atlas Network (HTAN), including 116 scRNA-seq datasets and clonal analysis of 418 human polyps, demonstrated the occurrence of polyancestral initiation in 15-30% of colonic precancers, revealing their origins from multiple normal founders. Thus, our multimodal framework augments existing single-cell analyses and lays the foundation forin vivomultimodal recording, enabling the tracking of lineage and temporal events during development and tumorigenesis.
Eco-anxiety among Children and Young People: Systematic Review of Social, Political, and Geographical determinants
Authors: Kankawale Shamal M , Niedzwiedz Claire L 
Published: December 2023

AbstractBackgroundEco-anxiety, the experience of challenging emotions relating to environmental issues, such as climate change, and the threats they present, is of increasing global public health concern. Although responses to eco-anxiety can be positive and motivational, experienced to a severe extent, they may contribute to depressive and anxiety disorders, exacerbate existing mental health conditions and negatively impact general wellbeing. Children and young people may be more susceptible to higher levels eco-anxiety, but the factors which contribute to eco-anxiety are not well-understood. This systematic review explored the social, political and geographical factors influencing eco-anxiety among children and young people.MethodsA comprehensive search of articles published between 2017-2023 was conducted on using EBSCOhost for APA PsycArticles, APA PsycInfo, Child Development & Adolescent Studies, CINAHL, EconLit, GreenFILE, Health Source: Nursing/Academic Edition, MEDLINE, Psychology and Behavioral Sciences Collection, and SocINDEX, with additional individual searches conducted on PubMed, Google Scholar, MedRxiv and PsyArxiv. The quality of included articles was assessed using the Joanna Briggs Institute (JBI) Checklist. The findings were summarised using a narrative synthesis approach.ResultsEighteen studies were included in the synthesis after screening 2,588 articles. Determinants in three major categories were identified: social (including age, gender, socioeconomic position, education, news and social media), political (climate activism, government inaction and sense of betrayal), and geographical factors (direct exposure to climate change-related events and country/region). Nine studies were cross-sectional, five were qualitative, three were mixed methods and one was longitudinal. Most studies were from high-income countries, particularly Australia, New Zealand and Norway. Studies were of variable methodological quality, using different measurement approaches to eco-anxiety and most surveys were conducted online using non-representative samples.ConclusionEco-anxiety is influenced by a range of social, political, and geographical factors. Governments and the mass media could play an important role in preventing eco-anxiety becoming of clinical concern. Given the lack of high-quality studies in this area, further research is essential to better understand the determinants of eco-anxiety across cultures to help minimize its impact on mental health and wellbeing and ensure it is channeled positively.
The actin-spectrin submembrane scaffold restricts endocytosis along proximal axons
Authors: Wernert Florian , Moparthi Satish , Lainé Jeanne , Moulay Gilles , Boroni-Rueda Fanny , Pelletier Florence , Jullien Nicolas , Benkhelifa-Ziyat Sofia , Papandréou Marie-Jeanne , Leterrier Christophe , Vassilopoulos Stéphane 
Published: December 2023

AbstractNeuronal clathrin-mediated endocytosis has unique features in compartments such as dendrites and presynaptic boutons, but how membrane and extracellular components are internalized along the axon shaft remains poorly known. Here we focused on clathrin-coated structures and endocytosis along the axon initial segment (AIS), and their relationship to the periodic actin-spectrin scaffold that lines the axonal plasma membrane. Super-resolution optical microscopy, platinum replica electron microscopy, and their correlative combination on cultured hippocampal neurons reveal that in the AIS, clathrin-coated pits form on bare membrane patches, ∼300 nm circular areas devoid of spectrin mesh and lined by actin filaments we termed “clearings”. In fibroblasts and the proximal axon of neurons, spectrin depletion and drug-induced scaffold disorganization increase clathrin-coated pit formation. However, the presence of clathrin-coated pits at the AIS is not directly linked to actual endocytosis: using cargo uptake and live-cell imaging experiments, we find that most AIS clathrin-coated pits are long-lived and immobile within the spectrin mesh clearings. Direct perturbation of the spectrin scaffold as well as elevated neuronal activity could induce endocytosis downstream of clathrin pit formation, showing that spectrin clearings are structures responsible for regulated endocytosis at the AIS.
A review of circular economy models and success factors on public-private partnership infrastructure development
Authors: Akomea-Frimpong Isaac , Jin Xiaohua , Osei Kyei Robert , Tetteh Portia Atswei , Tumpa Roksana Jahan , Ofori Joshua Nsiah Addo , Pariafsai Fatemeh 
Published: December 2023

PurposeThe application of circular economy (CE) has received wide coverage in the built environment, including public-private partnership (PPP) infrastructure projects, in recent times. However, current studies and practical implementation of CE are largely associated with construction demolition, waste and recycling management. Few studies exist on circular models and success factors of public infrastructures developed within the PPP contracts. Thus, the main objective of this article is to identify the models and key success factors associated with CE implementation in PPP infrastructure projects.Design/methodology/approachA systematic review of the literature was undertaken in this study using forty-two (42) peer-reviewed journal articles from Scopus, Web of Science, Google Scholar and PubMed.FindingsThe results show that environmental factors, sustainable economic growth, effective stakeholder management, sufficient funding, utilization of low-carbon materials, effective supply chain and procurement strategies facilitate the implementation of CE in PPP infrastructure projects. Key CE business models are centered around the extension of project life cycle value, circular inputs and recycling and reuse of projects.Research limitations/implicationsAlthough the study presents relevant findings and gaps for further investigations, it has a limited sample size of 42 papers, which is expected to increase as CE gain more prominence in PPP infrastructure management in future.Practical implicationsThe findings are relevant for decision-making by PPP practitioners to attain the social, economic and environmental benefits of transitioning to circular infrastructure management.Originality/valueThis study contributes to articulating the key models and measures toward sustainable CE in public infrastructure development.
Joint effect of entrepreneurship and dynamic capabilities on firm performance: an empirical investigation among ICT-SMEs
Authors: Nguyen Hoa Thi Nhu , Han Jung Woo , Pham Hiep Cong 
Published: December 2023

PurposeWith the focus on the context of small and medium-sized enterprises (SMEs), this study aims to investigate the joint effects of entrepreneurial leadership, entrepreneurial orientation and dynamic capabilities and the mechanisms of how these factors influence firm performance.Design/methodology/approachA survey from 319 managers in information and communications technology SMEs in Vietnam was conducted, and structural equation modeling was adopted to analyze the collected data.FindingsThe results confirm that dynamic capabilities directly influence firm performance and serve as a mediator that connects entrepreneurial leadership and entrepreneurial orientation with firm performance. Additionally, entrepreneurial leadership was found to have a significant positive impact on entrepreneurial orientation.Originality/valueThis research augments the understanding of entrepreneurship and dynamic capabilities literature by examining the joint effects and mechanisms of how entrepreneurial leadership, entrepreneurial orientation and dynamic capabilities interact to enhance SMEs' performance. Furthermore, this study provides empirical evidence of the strategies that SMEs should pursue to attain favorable performance outcomes.
Comparative life cycle assessment of flooring options for sustainable buildings
Authors: Choudhary Kailash , Sangwa Narpat Ram , Sangwan Kuldip Singh 
Published: December 2023

Purpose
This study aims to quantify and compare the environmental impacts of Marble-stone and Kota-stone flooring options widely used for buildings in India. The study discusses the possibility of carbon sequestration through Bamboo cultivation in India.

Design/methodology/approach
The study has followed a standard life cycle assessment (LCA) framework based on ISO 14040 guidelines. Three distinct phases have been compared on midpoint and endpoint assessment categories – raw material, polishing and disposal. Primary data has been collected from the construction site in India, and secondary data has been collected from the Ecoinvent 3.0 database. Previous studies have been referred to discuss and calculate the area of bamboo cultivation required to sequestrate the generated carbon from the flooring.

Findings
The study has found that endpoint category damage to resources, and midpoint categories of climate change, metal depletion and agricultural land use are highly impacted in building floorings. The study has also found that the Marble-stone floor generates higher environmental impacts than the Kota-stone floor in most of the midpoint and endpoint impact categories. This difference is significant in the raw material phase due to the different compositions of stones. The study also found that Bamboo has excellent potential to act as a carbon sink and mitigate the generated carbon.

Research limitations/implications
This study excludes human labour, cutting and distribution of floor tiles made of Marble-stone and Kota-stone. The researcher can use the study to evaluate, compare and benchmark the various building flooring options from the environmental perspective. The study aids to the body of knowledge available on the various building flooring options by presenting the LCA or the environmental impacts generated by two flooring options. It is expected that the architects and builders can use these results to develop carbon-neutral buildings. This study provides a methodology for governments, constructors, builders and individuals to evaluate, compare and benchmark the various construction materials from the environmental perspective by computing the environmental impacts throughout the life cycle of the materials.

Originality/value
This study compares two widely used building flooring options using the LCA methodology and evaluates the potential of bamboo cultivation near the buildings for carbon sinks. The study is unique because it shows the environmental impacts of two flooring options and the carbon sequestration method to mitigate/absorb the generated environmental impacts in or around the building itself through bamboo cultivation. This study may set the foundation for carbon-neutral buildings.
Situated between headquarters and local environment: local managers’ scope for action in training activities
Authors: Fuchs Martina , Westermeyer Johannes 
Published: December 2023

Purpose
The purpose of this paper is to explore the scope for action of local human resource managers, who are employed in foreign subsidiaries of multinational companies (MNCs), for implementing training activities. These managers are situated in relationships to headquarters and the local environment. Related to this is the question whether MNCs contribute to the local skill base by implementing training activities or whether they exploit the existing skill formation system.

Design/methodology/approach
This study focusses on German subsidiaries of MNCs with headquarters in the USA and the UK, France, China and Japan. The study is based on 107 expert interviews with subsidiary managers and representatives of local stakeholder organisations, such as educational organisations, chambers, economic promotion agencies and governmental bodies in Germany.

Findings
The study reveals that headquarters introduce general schemes for training. In addition to these MNC-internal trainings, local managers use their information advantage over headquarters to implement dual training activities.

Research limitations/implications
The training activities of subsidiaries are dependent on the institutional settings of the host country.

Practical implications
Albeit dual training activities are laborious and tie the local managers down for the medium and long term, the future need of the subsidiary for adequately skilled workforce prompts local managers’ engagement in implementing dual training activities.

Social implications
Subsidiaries contribute to the local skill base and do not act in a free-rider position, at least in the German variety of capitalism.

Originality/value
The study deepens insights on distanced relations within and how subsidiaries generate scope for action by using this kind of relationships.
Content analysis and sentiment analysis of pro- and anti-vaccine conversations on YouTube in India: intentions and causes
Authors: Kumar Vinit , Ji Gopal , Deori Maya , Verma Manoj Kumar 
Published: December 2023

Purpose
Vaccine hesitancy is a long-standing issue among both the general population and health communicators. This study aims to ascertain the inclination and the reasons for vaccine hesitancy by conducting content analysis and sentiment analysis of the perspectives expressed in comments on videos related to vaccine hesitancy uploaded from India on YouTube.

Design/methodology/approach
The assessment of the sentiments of the vaccine-hesitant population is done using Valence Aware Dictionary and sEntiment Reasoner sentiment analysis module implemented with Python’s NLTK library to automatically determine the sentiments of the comments. Manual content analysis was performed on 60.09% viewer comments randomly selected from the total comments in 238 videos on vaccine hesitancy originated from India and labelled each comment with labels “Anti”, “Pro”, “Confused”, “Not Applicable” and “Unrelated” labels.

Findings
The study found “Mistrust-Government policies”, “Fear-health related consequences”, “Mistrust-Scientific research”, “Vaccine effectiveness and efficacy” and “Misinformation/myths” as the top five determinants for vaccine hesitancy, whereas “Religious beliefs”, “Fear-Economic consequences”, “Side Effects- short-term” and “Fear-mode of administration” found to be the lesser cited reasons for vaccine hesitancy. However, the study also investigates changes in the inclination of Indian commenters towards vaccine hesitancy and revolving issues over time.

Social implications
Public health policymakers and health communicators may find the study useful in determining vaccine hesitancy factors in India.

Originality/value
The originality of this study lies in its approach. To date, no sentiment analysis has been conducted on the content released on YouTube by Indian content creators regarding pro- and anti-vaccination videos. This inquiry seeks to fill this research gap.