bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal enteroendocrine cell subtype differentiation and hormone production in zebrafish
Authors: Morash Margaret , Kay Richard G. , Soderblom Erik J. , MacLean Grace H. , Wen Jia , Moore Peyton J. , Lickwar Colin R. , Gribble Fiona M. , Reimann Frank , Liddle Rodger A. , Rawls John F. 
Published: January 2025

AbstractEnteroendocrine cells (EECs) are rare sensory cells in the intestinal epithelium that coordinate digestive physiology by secreting a diverse repertoire of peptide hormones. These hormones are the main effectors of EEC function, and their characterization requires direct observation by mass spectrometry due to the specialized protein cleavage and posttranslational modifications that yield their mature forms. Based on the distinct subset of hormones they predominantly secrete, EECs can be categorized into subtypes. How each EEC subtype is specified, however, remains poorly understood. Here we describe EEC subtype differentiation and hormone production in the zebrafish. Using single-cell RNA sequencing data, we identified EEC progenitors and six EEC subtypes in zebrafish and revealed that their expression profiles are consistent across larval and adult stages. Mass spectrometry analysis of isolated zebrafish EECs identified highly processed peptides derived from 18 of 21 hormone coding genes expressed by EECs, yielding a catalog of >400 unique EEC hormone peptides. We assembled reporters for zebrafish EEC subtypes to test the lineage relationships between EEC subtypes and the EEC progenitor population, which expressesneurogenin3. Despite its essential role in mammalian EEC differentiation, we found that selective cytotoxic ablation ofneurogenin3+ cells in zebrafish only reduced a subset of EEC subtypes. Finally, we discovered that selective ablation ofghrelin+ EECs reduced a different subset of EEC subtypes, together suggesting thatneurogenin3+ andghrelin+ cells serve as distinct precursors for separate EEC subtypes. We anticipate these observations and resources will facilitate future studies in the zebrafish to discern the developmental biology, physiology, and endocrinology of EEC subtypes.
Lipid-protecting disulfide bridges are the missing molecular link between ApoE4 and sporadic Alzheimer’s disease in humans
Authors: Ramsden Christopher E. , Cutler Roy G. , Li Xiufeng , Keyes Gregory S. 
Published: January 2025

AbstractAs the principal lipid transporter in the human brain, apolipoprotein E (ApoE) is tasked with the transport and protection of highly vulnerable lipids required to support and remodel neuronal membranes, in a process that is dependent on ApoE receptors. HumanAPOEallele variants that encode proteins differing only in the number of cysteine (Cys)-to-arginine (Arg) exchanges (ApoE2 [2 Cys], ApoE3 [1 Cys], ApoE4 [0 Cys]) comprise the strongest genetic risk factor for sporadic Alzheimer’s disease (AD); however, thespecificmolecular feature(s) and resultant mechanisms that underlie these isoform-dependent effects are unknown. One signature feature of Cys is the capacity to form disulfide (Cys-Cys) bridges, which are required to form disulfide bridge-linked dimers and multimers. Here we propose the overarching hypothesis that the super-ability (for ApoE2), intermediate ability (for ApoE3) or inability (for ApoE4) to form lipid-protecting intermolecular disulfide bridges, is the central molecular determinant accounting for the disparate effects ofAPOEalleles on AD risk and amyloid-β and Tau pathologies in humans. We posit that presence and abundance of Cys in human ApoE3 and ApoE2 respectively, conceal and protect vulnerable lipids transported by ApoE from peroxidation by enabling formation of ApoE homo-dimers/multimers and heteromeric ApoE complexes such as ApoE-ApoJ and ApoE-ApoD. We thus propose that the inability to form intermolecular disulfide bridges makes ApoE4-containing lipoproteins uniquely vulnerable to peroxidation and its downstream consequences. Consistent with our model, we found that brain-enriched polyunsaturated fatty acid-containing phospholipids induce disulfide-dependent dimerization and multimerization of ApoE3 and ApoE2 (but not ApoE4). By contrast, incubation with the peroxidation-resistant lipid DMPC or cholesterol alone had minimal effects on dimerization. These novel concepts and findings are integrated into our unifying model implicating peroxidation of ApoE-containing lipoproteins, with consequent ApoE receptor-ligand disruption, as the initiating molecular events that ultimately lead to AD in humans.HighlightsAPOEalleles are the strongest genetic risk factor for sporadic Alzheimer’s disease (AD)APOEalleles encode proteins that differ only in the number of Cys⟶Arg exchangesDespite 30 years of inquiry, mechanisms linking Cys⟶Arg exchanges to AD remain unknownPUFA-phospholipids induced disulfide bridge formation in ApoE3 and ApoE2 (but not ApoE4)We hypothesize that disulfide bridges in ApoE protect vulnerable lipids from peroxidationWe propose that lipid-protecting disulfide bridges explainAPOEallele-dependent AD risks
H3K27me3 and the PRC1-H2AK119ub pathway cooperatively maintain heterochromatin and transcriptional silencing after the loss of H3K9 methylation
Authors: Fukuda Kei , Shimura Chikako , Shinkai Yoichi 
Published: January 2025

AbstractHeterochromatin is a key architectural feature of eukaryotic chromosomes, essential for cell type-specific gene expression and genome stability. In the mammalian nucleus, heterochromatin is segregated from transcriptionally active euchromatic regions (A compartments), forming large, condensed, and inactive nuclear compartments (B compartments). However, the mechanisms underlying its spatial organization remain incompletely understood. Histone H3 lysine 9 and lysine 27 trimethylation (H3K9me3 and H3K27me3) are two major epigenetic modifications that enrich constitutive and facultative heterochromatin, respectively. Previously, we found that the redistribution of H3K27me3 following the loss of H3K9 methylation contributes to heterochromatin maintenance, while the simultaneous loss of both H3K27me3 and H3K9 methylation induces heterochromatin decondensation in mouse embryonic fibroblasts. However, nearly all B compartments were preserved despite the loss of these repressive chromatin modifications. These findings suggest that other factors are responsible for maintaining B compartments under these conditions. In this study, we explored the role of another repressive chromatin modification, PRC1-mediated H2A K119 monoubiquitylation (H2AK119ub/uH2A), in maintaining heterochromatin structure following the loss of H3K9/K27 methylation. We found that uH2A and H3K27me3 independently accumulate in the B compartments after the loss of H3K9 methylation in iMEFs and cooperatively maintain heterochromatin. Our data indicates that the PRC1-uH2A pathway contributes to maintain heterochromatin organization following the loss of H3K9/K27 methylation in mammalian cells.
KIDINS220 and InsP8 safeguard the stepwise regulation of phosphate exporter XPR1
Authors: Wang Xiaojie , Bai Zhongjian , Wallis Ciara , Wang Huanchen , Han Yaoyao , Jin Ruitao , Lei Mingguang , Yang Tian , Gu Chunfang , Jessen Henning , Shears Stephen , Sun Yadong , Corry Ben , Zhang Yixiao 
Published: January 2025

SummaryXPR1 is emerging as the only known inorganic phosphate (Pi) exporter in humans, critical for Pi homeostasis, with its activity stimulated by inositol pyrophosphate InsP8 and regulated by neuronal scaffold protein KIDINS220. Our structural studies reveal InsP8 specifically activates XPR1 in a stepwise manner, involving profound SPX domain movements. Each XPR1 subunit functions with four gating states, in which Pi permeates a constriction site via a “knock-kiss-kick” process. In contrast, KIDINS220 delicately stabilizes XPR1 in a closed conformation through multiple mechanisms, one of which involves trapping the XPR1 α1 helix—critical for InsP8 binding—within an interaction hub. InsP8 serves as a key to release KIDINS220’s restraint, reinforcing a “key-to-locks” mechanism to safeguard the stepwise activation. Additionally, our study provides direct structural insights into XPR1-associated neuronal disorders and highlights the evolutionary conservation and divergence among XPR1 orthologues, offering a comprehensive understanding of Pi homeostasis across species.
The Cancer Burden in the Abu Dhabi Population: A Retrospective Cohort Study
Authors: AlKetbi Latifa Baynouna , Ashoor Rawan , Saeed Ekram , AlShamsi Reem , Nagelkerke Nico , AlAlawi Noura , AlKetbi Rudina , Aleissaee Hamda , AlShamsi Noura , Humaid Ahmed , Abdulbaqi Hanan , Fahmawee Toqa , AlHashaikeh Basil , AlDobaee Muna , AlAhbabi Nayla , AlAzeezi AlYazia , Shuaib Fatima , Alnuaimi Jawaher , Mahmoud Esraa , AlMansoori Mohammed , AlKalbani Sanaa , AlDerie Wesayef , AlAhmadi Amira , Sahyouni Mohammad , AlAzeezi Maha 
Published: January 2025

AbstractBackgroundCancer is the third-leading cause of death in the United Arab Emirates (UAE). There are few studies on cancer epidemiology in the UAE.MethodsThis retrospective study, from 2011 to 2013 until 2023, aimed to estimate the prevalence of a history of cancer and lifetime risk and identify its risk factors.ResultsAmong 8635 cancer-free participants at the time of screening, 209 were diagnosed with new cancer (2.5%) over the follow-up period, 129 (1.9%) females compared to 80 (0.9%) males. The most common type of cancer was Breast cancer, with an incidence of 18% (37 cases) out of the 209 total cases, all females. The second most common type was Thyroid Cancer, with 31 cases; 24 of them were females, and 7 were males. The third most common type was colon cancer, with 22 cases, 11 females and 11 males. Other types of cancer were found but had lower incidence, such as Adrenal, skin cancer, ovarian, bladder, and gastrointestinal GI cancers. The prevalence was comparable to the latest published report of the Abu Dhabi cancer registry in 2019.Among the whole cohort, Cox regression analysis showed only age and higher levels of HDL as risk factors for any cancer after screening when including possible risk factors that were assessed at baseline. The risk increases by 4.8% for each year older and 52% for each unit increase in HDL. The area Under the ROC Curve of the developed model for predicting any cancer type is 0.739 (0.707-0.771).ConclusionThis study calls for focused research on different types of cancer to identify significant predictors to aid early diagnosis and management, as well as research on prevention and survival. This study’s results provide critical input to the country’s decision-makers on cancer services and are informative internationally as the risk factors identified are prevalent worldwide and may be targeted with available interventions.
Characterisation of 3000 patient reported outcomes with predictive machine learning to develop a scientific platform to study fatigue in Inflammatory Bowel Disease
Authors: Hall Rebecca , Whelan Robert J , Cartlidge Peter D , Brownson Emily F , Mowat Craig , Seenan John P , MacDonald Jonathan C , Campbell Iona AM , Chuah Cher S , Ho Gwo-Tzer 
Published: January 2025

AbstractBackgroundFatigue is commonly identified by IBD patients as major issue that affects their wellbeing. This presentation, however, is complex, multifactorial and mired in clinical heterogeneity.Aims/MethodsWe prospectively captured patient reported outcomes (PROs) from 2 current IBD biomarker studies in Scotland with ∼100 clinical metadata points; and an international dataset (that includes non-IBD healthy controls) using CUCQ32, a validated IBD questionnaire to generate a contemporaneous dataset of fatigue and overall wellbeing (2021-2024) and utilized 6 different machine learning (ML) approaches to predict IBD-associated fatigue and patterns that may aid future stratification to human mechanistic and clinical studies.ResultsIn 2 970 responses from 2 290 participants, CUCQ32 were higher in active IBD vs. remission; and in remission, higher than in non-IBD controls (both p<0.0001). CUCQ32-specific fatigue score significantly correlated to all CUCQ32 components (p=2.9 x 10-28to 3.2 x 10-147). During active IBD, patients had significantly more fatigue days compared to those in remission and non-IBD controls (medians 14 vs. 7 vs. 4 [out of 14 days]; both p<0.0001). We determine a threshold of ≥10/14 days of fatigue as clinically relevant - Fatiguehigh. Overall, 72.8% (863/1185), 45.0% (408/906) and 13.7% (46/355) responses in active, remission and non-IBD controls were in Fatiguehigh. Using train-validate-test steps, we incorporated all available metadata to generate ML-models to predict Fatiguehigh. The 6 ML models performed similarly (all 6 models AUC of ∼0.70). SHapley Additive exPlanations (SHAP) analysis revealed that each algorithm places different importance on variables with seasonality, biologic drug levels, BMI and gender identified as factors. ML prediction of Fatiguehighin patients in biochemical remission (CRP<5 mg/l and calprotectin <250μg/g) was more challenging with AUC of 0.66-0.61.ConclusionWe provide a comprehensive patient involvement-ML-pathway to predict IBD-associated fatigue. Our data suggests a large ‘hidden’ pathobiological component and current work is in progress to integrate deep molecular data and build a clinical-scientific ML model as a step towards better understanding of IBD-associated fatigue.
Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels
Authors: Cherdyntseva Veronica , Paulson Joanna , Adakli Selin , Gagné Jean-Philippe , Aouami Moses , Ubieto-Capella Patricia , González-Acosta Daniel , Bakker Collin , Poirier Guy G. , Taneja Nitika , Lopes Massimo 
Published: January 2025

AbstractMild replication interference is a consolidated strategy for cancer chemotherapy. Tolerance to mild replication stress (RS) relies on active fork slowing, mediated by transient fork reversal and RECQ1-assisted restart, and modulated by PARP1 and nuclear architectural components via yet-elusive mechanisms. We combined acute protein inactivation with cell biology and single-molecule approaches to investigate the role of Lamin A/C upon mild RS. We found that Lamin A/C dynamically interacts with replication factories throughout the nucleus and, together with its nucleoplasmic partner LAP2α, is required to induce active fork slowing and maintain chromosome stability upon mild genotoxic treatments. Inactivating nucleoplasmic Lamin A/C reduces poly-ADP-ribosylation (PAR) levels at nascent DNA, triggering deregulated RECQ1-mediated restart of reversed forks. Moreover, we found that the heterochromatin mark H3K9me3, previously reported at stalled forks, also accumulates in response to mild RS. H3K9me3 accumulation requires Lamin A/C, which prevents its premature removal by the histone demethylase JMJD1A/KDM3A. H3K9me3 lossper sephenocopies Lamin A/C inactivation, reducing PAR levels and deregulating RECQ1 activity at forks. Hence, nucleoplasmic Lamin A/C, H3K9me3 and PARylation levels are crucial, mechanistically-linked modulators of fork slowing, remodelling and restart upon mild RS, with important implications for chemotherapy response and Lamin A/C deregulation in human disease.
What causes investors’ misevaluation of M&A performance? Survey evidence from Japan
Authors: Amano Yoshiaki 
Published: January 2025

PurposeMotivated by literature suggesting that investors often misevaluate the effects of mergers and acquisitions (M&A), this study examines the relationship between investors' usage of information types/channels and their tendency to misevaluate M&A performance.Design/methodology/approachA survey methodology was employed to gather data from 1,000 individual investors in Japan. The survey focused on investors' evaluations of selected M&A transactions on announcement and response dates, grouping respondents into over-valuers, under-valuers and others based on changes in their evaluations.FindingsFirst, over-valuers are more likely to rely on earnings forecasts and synergy estimates, while under-valuers prioritize methods of payment and cultural or geographic distance. Second, those relationships between over- and under-valuation and information type usage are strengthened or weakened by different usage of information channels. Third, over-valuers regard information from securities firms as crucial when subsequently correcting their evaluations.Originality/valueThis study contributes to the literature on post-M&A underperformance by focusing on individual investor behaviors rather than aggregate stock market reactions. It also provides insights into how different types of information and channels influence investor evaluations, which has implications for M&A disclosure practices and standard setting.
Understanding the nexus between poverty and climate variability in Egypt
Authors: Abou-Ali Hala , Ramadan Racha , Elayouty Amira 
Published: January 2025

PurposeThis paper investigates the relationship between climate conditions and money-metric poverty in Egypt at a sub-national level, aiming to understand the nuanced impacts of environmental factors on household well-being.Design/methodology/approachEmploying a geographically weighted regression, the study analyzes data on climate conditions, socioeconomic indicators and poverty rates across different regions of Egypt.FindingsThe analysis reveals complex relationships between climate conditions, socioeconomic factors, and poverty rates in Egypt. Higher education, asset ownership and urban residence are associated with lower poverty rates, while larger household size correlates with increased poverty. Temperature and precipitation show varied impacts on poverty between extreme and average climate conditions and across different regions, highlighting the need for localized strategies.Practical implicationsThe findings underscore the importance of tailored interventions to address the localized impacts of climate change on poverty. Policymakers can use the insights from this research to prioritize vulnerable areas and implement targeted measures to alleviate poverty and enhance climate resilience.Social implicationsBy identifying areas most susceptible to climate change, this research informs policies aimed at protecting marginalized communities from its adverse effects. It contributes to broader efforts to promote social equity and environmental sustainability in Egypt.Originality/valueThis paper provides a comprehensive analysis of the climate–poverty nexus in Egypt, offering insights into the localized impacts of climate change on household well-being. The findings contribute to both academic discourse and policy development, guiding efforts to address poverty and climate vulnerability at the regional level.Peer reviewThe peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-04-2024-0317
From purchase to regret: deterring counterfeit consumption through moral emotions and multicultural identity
Authors: Shi Linda Hui , Cui Annie Peng , Fitzsimmons Stacey 
Published: January 2025

PurposeThis research examines whether conflicting multicultural identities may influence counterfeit consumption behavior by examining how monocultural and multicultural consumers process shame and guilt differently depending on their cultural identities. It explores how consumers’ moral emotions after buying counterfeit goods can lead to regret and reduce their likelihood of buying such goods in the future.Design/methodology/approachThis research employs a multimethod, multi-sample approach with 1,694 respondents across multiple cultures to test our hypotheses. Study 1 is survey research with overseas Chinese consumers and monocultural Chinese consumers, and Study 2 is a randomized block experiment with a European multicultural sample. This design allowed us to test both mediation and moderation hypotheses, validating the effects of shame and guilt on post-purchase regret across diverse multicultural settings.FindingsStudy 1 shows that cultural identity conflict (CIC) weakens the main effects of shame and guilt on counterfeit post-purchase regret. Study 2 shows that under artificially high levels of shame and guilt, CIC no longer weakens the effects of either shame or guilt on post-purchase regret, further confirming these main effects on counterfeit post-purchase regret. Furthermore, Study 2 demonstrates that, in a natural setting without manipulation, CIC weakens the main effects of shame and guilt on post-purchase regret, further supporting CIC’s moderating effect.Originality/valueThis study develops a model to examine counterfeit purchasing, going beyond the point of purchase to also consider post-purchase regret and repurchase intentions. It also explores moral emotions and cultural identity factors that can discourage future counterfeit purchases by increasing post-purchase regret. Finally, it investigates how this process may vary between multicultural and monocultural consumers, given their different cultural identities.
The unfolding of geopolitical tensions on social networks: a social network analysis of Twitter and Reddit conversations
Authors: Vasist Pramukh Nanjundaswamy , Krishnan Satish , Agnihotri Prafulla 
Published: January 2025

PurposeSocial networks can not only mobilize individuals for collective action but also pose risks, potentially leading to political challenges and societal unrest. Information consumption varies across platforms, with platform characteristics influencing user interactions and information sharing; yet this has received limited attention in scholarly literature. Acknowledging platform-specific differences, this paper seeks to enhance our understanding of the mechanisms driving information diffusion on social networks in the context of geopolitical tensions.Design/methodology/approachThe structural communication features on Twitter and Reddit are explored using schema theory and the concept of social media platform schema. Comparisons are drawn with social network analysis and content analysis of communication dynamics surrounding geopolitical tensions in India–Qatar relations, followed by the context of geopolitical tensions between India and Pakistan.FindingsThe results illustrate how content-based connections on Reddit foster closer ties within subreddits but less connectivity between them, contrasting with Twitter’s profile-based connections. These distinct characteristics lead to varied information diffusion patterns and shape the diversity of opinions, influencing community structures and affecting the emotional tenor of discourse.Originality/valueSocial networks can potentially influence geopolitical events, but focusing on one platform overlooks differences in how information spreads and the influence each platform holds. Recognizing this, our comparative analysis of social networks’ structural attributes highlights their crucial roles in shaping user engagement and information diffusion. It lends theoretical support to the notion of social media platform schema with empirical insights into how users’ perceptions of these schemas impact thematic and emotional differences in platform discourse related to geopolitical tensions.