bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of chromatin via H3K27 methylation underpins differentiation arrest in Isocitrate dehydrogenase-mutant Acute Myeloid Leukaemia
Authors: Silveira Douglas RA , Chatzikyriakou Prodromos , Casares Aláez Pilar , Mackie Sarah , Hulks Roan , Yavorska Olena , Siejka-Zielińska Paulina , Smith Alastair , Metzner Marlen , Usukhbayar Batchimeg , Penard-Lacronique Virginie , Song Chun-Xiao , Gandhi Anita K. , Vyas Paresh , Milne Thomas A. , Kriaucionis Skirmantas , Hasan Maroof , Quek Lynn 
Published: August 2023

ABSTRACTDysregulation of cellular differentiation is a hallmark of cancer. Isocitrate dehydrogenase (IDH) is commonly mutated multiple cancers including glioma, cholangiocarcinoma, lymphoma and Acute Myeloid Leukaemia (AML). Mutant IDH generates d-2-hydroxyglutarate that inhibits enzymes including Jumonji histone demethylases and TET2. Using primary human IDH2-mutant AML cells as a model, single cell RNA-seq and ATAC-seq, we demonstrated the continuum of cell states during restoration of neutrophilic differentiation to leukaemic progenitors by Enasidenib, a mutant IDH2 inhibitor. In cells which ultimately differentiate, there is co-expression of competing GATA2/RUNX3/SOX4-driven stem-progenitor and pro-differentiation EGR1/JUN/FOS programmes, followed by expression of cell cycle and terminal neutrophil programmes involving CEBP family and SPI1/PU.1. Genes upregulated during differentiation display loss of H3K27me3 in bivalent chromatin but not of H3K4me3, while downregulated genes are enriched for PRC2/EZH2 targets. In contrast to previous reports of a TET2-dependent mechanism for IDH-mutations, we observed only a modest link between promoter DNA CpG methylation and gene expression. For the first time in primary AML, we describe the lifting of differentiation block by de-repression of pro-differentiation genes through modulation of H3K27 demethylation in bivalent chromatin, and thus highlight a novel and important mechanism in how IDH mutations disrupt cell fates in cancer.
Disruption of Aldehyde Dehydrogenase 2 protects against bacterial infection
Authors: Berry Samuel B. , Espich Scott , Thuong Nguyen T.T. , Chang Xuling , Dorajoo Rajkumar , Khor Chiea-Chuen , Heng Chew-Kiat , Yuan Jian-Min , Fox Douglas , Anaya-Sanchez Andrea , Tenney Logan , Chang Christopher J. , Kotov Dmitri I. , Vance Russell E. , Dunstan Sarah J. , Darwin K. Heran , Stanley Sarah A. 
Published: August 2023

AbstractTheALDH2*2(rs671) allele is one of the most common genetic mutations in humans, yet the positive evolutionary selective pressure to maintain this mutation is unknown, despite its association with adverse health outcomes. ALDH2 is responsible for the detoxification of metabolically produced aldehydes, including lipid-peroxidation end products derived from inflammation. Here, we demonstrate that host-derived aldehydes 4-hydroxynonenal (4HNE), malondialdehyde (MDA), and formaldehyde (FA), all of which are metabolized by ALDH2, are directly toxic to the bacterial pathogensMycobacterium tuberculosisandFrancisella tularensisat physiological levels. We find thatAldh2expression in macrophages is decreased upon immune stimulation, and that bone marrow-derived macrophages fromAldh2–/–mice contain elevated aldehydes relative to wild-type mice. Macrophages deficient forAldh2exhibited enhanced control ofFrancisellainfection.Finally, mice lackingAldh2demonstrated increased resistance to pulmonary infection byM. tuberculosis, including in a hypersusceptible model of tuberculosis, and were also resistant toFrancisellainfection. We hypothesize that the absence of ALDH2 contributes to the host’s ability to control infection by pathogens such asM. tuberculosisandF. tularensis, and that host-derived aldehydes act as antimicrobial factors during intracellular bacterial infections.One sentence summaryAldehydes produced by host cells contribute to the control of bacterial infections.
Two functionally distinct HEATR5 protein complexes are defined by fast-evolving co-factors in yeast
Authors: Marmorale Lucas J. , Jin Huan , Reidy Thomas G. , Palomino-Alonso Brandon , Zysnarski Christopher , Jordan-Javed Fatima , Lahiri Sagar , Duncan Mara C 
Published: August 2023

AbstractThe highly conserved HEATR5 proteins are best known for their roles in membrane traffic mediated by the adaptor protein complex-1 (AP1). HEATR5 proteins rely on fast-evolving co-factors to bind to AP1. However, how HEATR5 proteins interact with these co-factors is unknown. Here, we report that the budding yeast HEATR5 protein, Laa1, functions in two biochemically distinct complexes. These complexes are defined by a pair of mutually exclusive Laa1-binding proteins, Laa2 and the previously uncharacterized Lft1/Yml037c. Despite limited sequence similarity, biochemical analysis and structure predictions indicate that Lft1 and Laa2 bind Laa1 via structurally similar mechanisms. Both Laa1 complexes function in intra-Golgi recycling. However, only the Laa2-Laa1 complex binds to AP1 and contributes to its localization. Finally, structure predictions indicate that human HEATR5 proteins bind to a pair of fast-evolving interacting partners via a mechanism similar to that observed in yeast. These results reveal mechanistic insight into how HEATR5 proteins bind their co-factors and indicate that Laa1 performs functions besides recruiting AP1.
WITHDRAWN: Mapping miRNA regulation of MGAT3 reveals upregulation as the dominant mode of action
Authors: Zohora Fatema Tuz , Batu Tigist Tesfaye , Mahal Lara K. 
Published: August 2023

Withdrawal StatementThe authors have withdrawn their manuscript owing to issues of cloning in the original pFmiR-MGAT3 sensor which make the data profiling miRNA regulation of this gene inaccurate. As a result, any miRNA identified should be disregarded and the data is invalid. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma
Authors: Augustin Ryan C. , Newman Sarah , Li Aofei , Joy Marion , Lyons Maureen , Pham Mary , Lucas Peter C. , Smith Kate , Sander Cindy , Isett Brian , Davar Diwakar , Najjar Yana G. , Zarour Hassane M. , Kirkwood John M. , Luke Jason J. , Bao Riyue 
Published: August 2023

AbstractBackgroundAcral melanoma (AM) has distinct characteristics as compared to cutaneous melanoma and exhibits poor response to immune checkpoint inhibitors (ICI). Tumor-intrinsic mechanisms of immune exclusion have been identified in many cancers but less studied in AM.MethodsWe characterized clinically annotated tumors from patients diagnosed with AM at our institution in correlation with ICI response using whole transcriptome RNAseq, whole exome sequencing, CD8 immunohistochemistry, and multispectral immunofluorescence imaging. A defined interferon-γ-associated T cell-inflamed gene signature was used to categorize tumors into non-T cell-inflamed and T cell-inflamed phenotypes. In combination with AM tumors from two published studies, we systematically assessed the immune landscape of AM and detected differential gene expression and pathway activation in a non-T cell-inflamed tumor microenvironment (TME). Two single-cell(sc) RNAseq AM cohorts and 11 bulk RNAseq cohorts of various tumor types were used for independent validation on pathways associated with lack of ICI response. In total, 892 specimens were included in this study.Results72.5% of AM tumors showed low expression of the T cell-inflamed gene signature, with 23.9% of total tumors categorized as the non-T cell-inflamed phenotype. Patients of low CD3+CD8+PD1+intratumoral T cell density showed poor prognosis. We identified 11 oncogenic pathways significantly upregulated in non-T cell-inflamed relative to T cell-inflamed TME shared across all three acral cohorts (MYC, HGF, MITF, VEGF, EGFR, SP1, ERBB2, TFEB, SREBF1, SOX2, and CCND1). scRNAseq analysis revealed that tumor cell-expressing pathway scores were significantly higher in low vs high T cell-infiltrated AM tumors. We further demonstrated that the 11 pathways were enriched in ICI non-responders compared to responders across cancers, including acral melanoma, cutaneous melanoma, triple-negative breast cancer, and non-small cell lung cancer. Pathway activation was associated with low expression of interferon stimulated genes, suggesting suppression of antigen presentation. Across the 11 pathways, fatty acid synthase and CXCL8 were unifying downstream target molecules suggesting potential nodes for therapeutic intervention.ConclusionsA unique set of pathways is associated with immune exclusion and ICI resistance in AM. These data may inform immunotherapy combinations for immediate clinical translation.
GENESIS CGDYN: large-scale coarse-grained MD simulation with dynamic load balancing for heterogeneous biomolecular systems
Authors: Jung Jaewoon , Tan Cheng , Sugita Yuji 
Published: August 2023

AbstractResidue-level coarse-grained (CG) molecular dynamics (MD) simulation is widely used to investigate slow biological processes that involve multiple proteins, nucleic acids, and their complexes. Biomolecules in a large simulation system are distributed non-uniformly, limiting computational efficiency with conventional methods. Here, we develop a hierarchical domain decomposition scheme with dynamic load balancing for heterogeneous biomolecular systems to keep computational efficiency even after drastic changes in particle distribution. The new schemes are applied to intrinsically disordered protein (IDP) droplet fusions. The droplet shape changes correlate with mixing IDP chains from two droplets. We also simulate formations of large IDP droplets, whose sizes are almost equivalent to those observed in microscopy. The methods have been implemented in CGDYN of the GENESIS software, which provides a new tool for investigating mesoscopic biological phenomena using the residue-level CG models.
Exposure to titanium dioxide nanoparticles accelerates abnormal fat deposition through the mediation of the ROS via the AGE-RAGE signaling pathway in mice
Authors: Liu Jingyi , Zhong Liang , Yuan Tiantian , Sun Jingchun , Wang Yaxin , Chen Jiahao , Yang Gongshe , Yu Taiyong 
Published: August 2023

AbstractTitanium dioxide nanoparticles (TiO2NPs) are widely added to various types of foods as food additives. Previous studies have shown that TiO2NPs exposure can cause abnormal deposition of adipose tissue in organisms, resulting in lipid metabolism disorder. However, the potential molecular mechanisms underlying TiO2NPs’ effects have yet to be elucidated. In this study, our data indicated that TiO2NPs (100 mg/Kg BW, 20 nm) accelerated abnormal fat deposition in the epididymal adipose tissues and disturbed the level of blood glucose subsequently in normal-fat diet mice. Further studies showed that TiO2NPs at a concentration of 100 µg/mL significantly induced the proliferation and differentiation of 3T3-L1 preadipocytes. Mechanistic studies we revealed that TiO2NPs induced the overproduction of reactive oxygen species (ROS) in the cytoplasm, which subsequently upregulated the expression of receptors for advanced glycation end products (AGEs) leading to lipid accumulation in the adipocytes with a higher level of ROS. However, the antioxidant N-acetylcysteine (NAC) was a therapeutic potential for lipid overaccumulation in the adipocytes. This study provides insight into the mechanism underlying fat deposition induced by TiO2NPs and highlighted the need for reevaluation of food-grade TiO2NPs exposure in daily life.
Determinants of health-related quality of life in healthy children and adolescents during the COVID-19 pandemic: results from a prospective longitudinal cohort study
Authors: Haile Sarah R , Peralta Gabriela P , Raineri Alessia , Rueegg Sonja , Ulyte Agne , Puhan Milo A , Radtke Thomas , Kriemler Susi 
Published: August 2023

AbstractPurposeUnderstanding health-related quality of life (HRQOL) in children and adolescents, during a pandemic and afterwards, aids in understanding how circumstances in their lives impact their well-being. We aimed to identify determinants of HRQOL from a broad range of biological, psychological and social factors in a large longitudinal population-based sample.MethodsData was taken from a longitudinal sample (n = 1843) of children and adolescents enrolled in the prospective school-based cohort studyCiao Coronain Switzerland. The primary outcome was HRQOL, assessed using the KINDL total score and its subscales (each from 0, worst, to 100, best). Potential determinants, including biological (physical activity, screen time, sleep, etc), psychological (sadness, anxiousness, stress) and social (nationality, parents’ education, etc) factors, were assessed in 2020 and 2021, and HRQOL in 2022. Determinants were identified in a data-driven manner using recursive partitioning to define homogeneous subgroups, stratified by school level.ResultsMedian KINDL total score in the empirically identified subgroups ranged from 68 to 83 in primary school children and from 69 to 82 in adolescents in secondary school. The psychological factors sadness, anxiousness and stress in 2021 were identified as the most important determinants of HRQOL in both primary and secondary school children. Other factors, such as physical activity, screen time, chronic health conditions or nationality, were determinants only in individual subscales.ConclusionRecent mental health, more than biological, physical or social factors, played a key role in determining HRQOL in children and adolescents during pandemic times. Public health strategies to improve mental health may therefore be effective in improving HRQOL in this age group.What is knownAssessing health-related quality of life (HRQOL) in children and adolescents aids in under- standing how life circumstances impact their well-being.HRQOL is a complex construct, involving biological, psychological and social factors. Factors driving HRQOL in children and adolescents are not often studied in longitudinal population-based samples.What is newMental health (stress, anxiousness, sadness) played a key role in determining HRQOL during the coronavirus pandemic, more than biological or social factors.Public health strategies to improve mental health may be effective in improving HRQOL in children.
Differential Regulation of Excitatory vs Inhibitory Synaptic Release by Complexin/CPX-1 and CAPS/UNC-31 at theC. elegansNeuromuscular Junctions
Authors: Wang Ya , Chow Chun Hin , Huang Mengjia , Higazy Randa , Ramakrishnan Neeraja , Zhang Cuntai , Sugita Shuzo , Gao Shangbang 
Published: August 2023

AbstractThe excitation and inhibition (E/I) balance at neuromuscular junctions plays a crucial role in coordinating animal motor behavior. Prominent synaptic vesicle secretory regulatory proteins, specifically complexin and CAPS (Calcium-dependent Activator Protein for Secretion), have not garnered sufficient attention for E/I balance regulation. Here, we investigate the roles of complexin/CPX-1 and CAPS/UNC-31 in excitatory vs inhibitory synapses ofC. elegansneuromuscular junctions. In our study,cpx-1null mutants displayed remarkable reduction evoked release in both excitatory and inhibitory synapses. Intriguingly, these mutants exhibited an enhanced level of spontaneous release, particularly within the context of excitatory synapse. This enhancement aligns with its “clamp” role that preventing SV from fusing with the presynaptic membrane. Additionally, a clamping-specific knockin mutantcpx-1(Δ12), which displayed no alterations in evoked release at either type of synapse, also revealed a biased substantial increase in excitatory spontaneous release. In contrast,unc-31null mutation, with normal spontaneous release, led to a more pronounced decreased evoked release in the excitatory synapse independent of dense-core vesicle regulation. Intriguingly, we found that the enhanced excitatory spontaneous release observed incpx-1mutants was abolished byunc-31in a Ca2+-dependent manner, implying that UNC-31 is essential for maintaining a high level of spontaneous fusion events. Collectively, our findings unveil a distinct regulatory pattern governing excitatory and inhibitory synaptic release, orchestrated by the interplay of CPX-1 and UNC-31. Notably, we uncover an unforeseen role of UNC-31 in influencing CPX-1’s “clamp” function, further adding complexity to the neural dynamics, which may underlie complex behavioral phenotypes observed inC. elegans.
Consumer responses to sustainable product branding strategies: a literature review and future research agenda
Authors: Fatemi Hajar , Leijerholt Ulrika , Rezvani Zeinab , Schnittka Oliver 
Published: August 2023

PurposeThis literature review aims to synthesise the research on various sustainable product branding activities and their impact on consumer responses to sustainable products and brands.Design/methodology/approachThis literature review is semi-systematic and can be classified as a domain-based review. The search strategy was systematic and well-defined.FindingsThe authors identified four themes: building brand equity, brand communication, product development and third-party labels and ratings, within the sustainable product branding activities that influence consumers' responses to sustainable products and brands. The study's findings revealed diverse, and not always favourable, types of behavioural and attitudinal responses from consumers. As for the positive consumer responses, the authors found positive attitudes towards brands, willingness to pay a premium price and positive word-of-mouth intentions. As for the negative consumer responses, the authors found perceived greenwashing, negative brand evaluations and resistance to sustainable products with unfamiliar third-party labels. Several future research propositions and implications for research and practice are discussed.Originality/valueDespite the large number of studies that look at sustainable branding strategies, there is a gap in terms of synthesising the knowledge on consumer responses to sustainable product branding strategies. This paper intends to fill this gap.
Performance-oriented HR and career development of women managers: the mediation of self-leadership and the moderated mediation of supervisor’s gender equality
Authors: Joo Jaehong , Kim Hee Sun , Song Sae Gyoung , Ro Yun Jeong , Song Ji Hoon 
Published: August 2023

Purpose
The purpose of this study is to emphasize the important role of performance-oriented human resource (HR) practices and gender equality perceptions in supervisors and chief executive officers (CEOs) for career development among women in management.

Design/methodology/approach
This study used a quantitative methodology to examine relationships among variables. The authors conducted a survey to investigate factors influencing the career development of women managers in professional settings, with a sample of 1,502 female managers in South Korea.

Findings
The relationship between performance-oriented HR practices and career development for women managers was supported. In addition, self-leadership significantly mediated the relationship between performance-oriented HR practices and career development. Finally, double moderator effects of gender equality perceptions of CEOs and supervisors on the relationship between performance-oriented HR practices and self-leadership were significant.

Originality/value
This study emphasizes that career development for women in South Korea depends on gender equality awareness and institutional reorganization for best practices at top management levels. Specifically, this study identified the essential role of performance-based HR practices to support self-leadership and career development in women managers. Furthermore, this study recognized gender equality perceptions of CEOs and supervisors as a critical factor in the successful career development of women managers.
Exploring Indian working mothers' transition to involuntary telecommuting
Authors: Javad Shahina , Nema Priyanka , Chowdhary Nimit 
Published: August 2023

PurposeDuring the COVID-19 pandemic, many working mothers in India adopted involuntary telecommuting work option for the first time. However, no research explored their adjustments and experiences in the new work setting. This paper aims to gain an in-depth understanding of Indian working mothers' lived experience of involuntary telecommuting.Design/methodology/approachA phenomenological research design was adopted. The authors conducted 14 in-depth, semi-structured telephonic and online interviews. Data were analyzed using Interpretative Phenomenological Analysis framework.FindingsThe data analysis yielded two interconnected superordinate themes in this research: (1) characteristics of involuntary telecommuting and (2) the impact of involuntary telecommuting. Under the first theme, four sub-themes emerged: long working hours, increased family demands, reduced interaction with coworkers and technology-enabled communication with supervisors. The second theme comprised five sub-themes: time-based work interference with family, time-based family interference with work, strain-based family interference with work, absence of emotional and professional support and performance management concerns. Involuntary telecommuting mothers faced challenges due to lack of control over their daily work schedule and demands, along with an increased burden of unpaid household work, leading to difficulties in managing their work schedule and negotiating their professional role identity within the family. These findings emphasize that working mothers who participated in involuntary telecommuting encountered bidirectional time-based conflicts and unidirectional strain-based conflict.Research limitations/implicationsThe study examines a particular subset of women telecommuters who were working mothers with young children. These potential limitations are to be addressed in future research.Practical implicationsThe findings suggest that managers should develop HR policies and telecommuting ecosystems in order to enhance effectiveness of telecommuting. Specifically, organizations offering telecommuting work options should create opportunities for informal interaction among peers and formal one-to-one interaction with managers. Moreover, HR managers should develop and implement employee-friendly telecommuting policies.Social implicationsThe research contributes to HRM and gender literature.Originality/valueThe paper contributes to the discourses of work-life balance, workplace relationships and work policies within telecommuting literature.
Ghana's textile and apparel sector: a strategic assessment of skills needs and development through the STED framework
Authors: Anyigba Hod , Preko Alexander , Senayah William Kwesi 
Published: August 2023

PurposeThis study is to examine and develop sector skills strategies and action plans for the textile and apparel (T&A) sector.Design/methodology/approachThe paper used a participatory action qualitative method anchored on the Skills for Trade and Economic Diversification (STED) framework, utilising the workshop-based approach with 24 key stakeholders of the sector. Content analysis was used with the help of Nvivo software.FindingsThe findings revealed that there are skills shortages, skills gaps, skills mismatches and skills diversification programmes available through higher education and work-based learning. Further, there are labour supply challenges such as national skills policy and strategy, government and stakeholder coordination, funding, relevance of curriculum and qualifications, access to practicals and the absence of a clear national vision for the sector.Research limitations/implicationsThis study possesses an inherent limitation in terms of generalising the findings derived from qualitative research.Originality/valueThis research is among the first of its kind to assess skills needs and gaps through the lens of STED framework, which has been overlooked in previous literature. Importantly, this study provides vocational insights into skill needs in the sector.