bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in colonic inflammation are driven by epithelial-specific expression of estrogen receptor alpha
Authors: Pereda Guillermo A. , Kocinski Adrian D. , Broncano Alyssia V. , McNeer Sarah K. , Raymond Michelle L. , Ziats Nicholas P. , Breau Keith A. , Burclaff Joseph , Magness Scott T. , Goodman Wendy A. 
Published: October 2024

ABSTRACTBackground & AimsInflammatory bowel disease (IBD) patients exhibit altered expression of nuclear estrogen receptors alpha and beta (ERα, ERβ) and G-protein coupled estrogen receptor 1 (GPER1). We previously showed that deletion of ERα protects against intestinal damage selectively in female mice; however, the mechanisms conferring sex-specific protection are poorly understood. The goal of this study was to compare ERα- and ERβ-specific mechanisms contributing to intestinal epithelial function in males and females.MethodsExpression of ERα, ERβ, and GPER1 was evaluated in colonocytes from wild-type (WT) male and female mice. Intestinal epithelial cell (IEC)-specific ERα and ERβ knockout mice were developed and challenged with dextran sulfate sodium (DSS). Colonic organoids were used to identify estrogen-dependent and -independent effects on cellular growth, differentiation, and transcriptional regulation in WT, ERα-KO, and ERβ-KO IECs.ResultsColonic IECs showed significant expression of ERα, ERβ, and GPER1 as well as Cyp19A1, which catalyzes production of 17β-estradiol (estrogen). Female mice lacking ERα specifically in colonic IECs showed protection from DSS-induced injury, whereas males showed increased pathology. Organoids derived from male ERα-KO mice showed enhanced proliferation and decreased expression of key functional genes even without exogenous estrogen; however, colonoids derived from female ERα-KO mice transcriptional analysis showed a protective gene signature. These findings reveal that deletion of ERα differentially contributes to enhanced barrier function and resistance to inflammation in females, but to dysfunctional hyper-proliferation in males.ConclusionsERα signaling within IECs drives opposing sex-dependent effects on the development, regenerative capacity, and inflammatory susceptibility of the intestinal epithelium.
Direct and Indirect Regulation of SIX1+EYA Transcriptional Activity by PA2G4, MCRS1, and SOBP
Authors: Jourdeuil Karyn , Gafurova Jasmina , Ben-Mayor Ashley , Moody Sally A. , Tavares Andre L. P. 
Published: October 2024

AbstractBranchio-oto-renal (BOR) syndrome is an autosomal dominant condition characterized by variable craniofacial malformations, hearing loss and in some patients, renal dysfunction. Recently, a clinical study showed that patients with mutations causative of BOR also present with craniosynostosis, indicating that this could be an undiagnosed feature of BOR. Approximately half of all patients presenting with BOR have a variant in eitherSIX1or its activating co-factorEYA1. The genes underlying BOR in the other 50% of patients remain unknown. To date, most studies on the role of SIX1 in the inner ear have focused on its role in the placode-based development of the sensorineural epithelia (cochlear and vestibular organs), as sensorineural hearing loss has long term effects on human health and development. The role of SIX1 in the neural crest cells (NCCs) of the first pharyngeal (a.k.a., mandibular) arch, which will give rise to the upper and lower jaws as well as the middle ear ossicles which may be affected in patients with BOR, is less well understood. To that end, we examine herein the role of three proteins that have been identified inXenopus laevisas SIX1 co-factors to determine whether their function as regulators of SIX1+EYA transcriptional activity is conserved in mouse and begin to elucidate their function in the NCCs of the mandibular arch. Our data reveal that SIX1 is co-expressed with PA2G4, MCRS1, and SOBP within the oral domain of the mandibular arch, although each has a very distinct expression pattern. We further demonstrate that MCRS1 and SOBP arebona fideSIX1 co-factors that can repress SIX1+EYA transcriptional activity. PA2G4, on the other hand, does not bind to SIX1 in the mouse but can indirectly enhance the transcriptional activity of the SIX1+EYA transcriptional complex. Further, we show that both MCRS1 and SOBP are also able to translocate EYA to the nucleus via direct (i.e., SOBP) or indirect (i.e., MCRS1) mechanisms. We also show that later, during development of the mandible and incisors that SOBP is co-expressed with SIX1 within these anlagen, confirming the biological relevance of these transcriptional complexes in craniofacial bone formation and within the derivatives of the mandibular NCCs. This study, therefore, highlights the complexity of SIX1+EYA transcriptional regulation suggesting that there are multiple, and potentially redundant, mechanisms in place to ensure precise levels of SIX1+EYA transcriptional activity during craniofacial development.
Aladyn Individual: Bayesian Hierarchical Dynamic Genetic Modeling of Comorbidity Progression
Authors: Urbut Sarah , Ding Yi , Jiang Xilin , Hornsby Whitney , Gusev Alexander , Natarajan Pradeep , Parmigiani Giovanni 
Published: October 2024

AbstractEarly identification of high-risk individuals through the analysis of their unique disease trajectories has a strong potential to support efficient prevention and clinical management across a range of chronic conditions. In this paper we present a novel approach for dynamic modeling of the evolution of chronic disease risks over time, incorporating individual genetic predispositions. Our approach uses a hierarchical Bayesian topic model including Gaussian Processes to capture age effects. It accounts for genetic predisposition through a time-warping function and topic-dependent genetic scores, enabling both simultaneous learning and updated predictions of complex comorbidity patterns, inclusive of genomic and non-genomic effects. We systematically compare to previous approaches and provide detailed simulations athttps://bookdown.org/sarahmurbut/dynamic_ehr/andhttps://surbut.shinyapps.io/dynamic_ehr.Impact StatementOur model significantly advances healthcare for aging populations by facilitating the early identification of high-risk individuals through the analysis of their unique disease trajectories within complex comorbidity patterns. Existing models are limited in their capacity to manage diverse comorbidity patterns, particularly those that are time-dependent. We introduce an approach leveraging Bayesian hierarchical modeling to concurrently learn population-level patterns and provide updated real-time predictions across 350 diseases, thereby uncovering and forecasting intricate comorbidity patterns. This methodology paves the way for preventive measures and targeted interventions that enhance health outcomes, mitigate late-stage disease burdens, and foster healthier aging. Furthermore, our model incorporates genetic influences via a genetic predisposition parameter to estimate the lifetime risk of specific diseases and disorders, alongside a time-warping function to facilitate personalized predictions of disease trajectories.
R2DT: a comprehensive platform for visualising RNA secondary structure
Authors: McCann Holly , Meade Caeden D. , Williams Loren Dean , Petrov Anton S. , Johnson Philip Z. , Simon Anne E. , Hoksza David , Nawrocki Eric P. , Chan Patricia P. , Lowe Todd M. , Ribas Carlos Eduardo , Sweeney Blake A. , Madeira Fábio , Anyango Stephen , Appasamy Sri Devan , Deshpande Mandar , Varadi Mihaly , Velankar Sameer , Zirbel Craig L. , Naiden Aleksei , Jossinet Fabrice , Petrov Anton I. 
Published: October 2024

ABSTRACTRNA secondary (2D) structure visualisation is an essential tool for understanding RNA function. R2DT is a software package designed to visualise RNA 2D structures in consistent, recognisable, and reproducible layouts. The latest release, R2DT 2.0, introduces multiple significant features, including the ability to display position-specific information, such as single nucleotide polymorphisms (SNPs) or SHAPE reactivities. It also offers a new template-free mode allowing visualisation of RNAs without pre-existing templates, alongside a constrained folding mode and support for animated visualisations. Users can interactively modify R2DT diagrams, either manually or using natural language prompts, to generate new templates or create publication-quality images. Additionally, R2DT features faster performance, an expanded template library, and a growing collection of compatible tools and utilities. Already integrated into multiple biological databases, R2DT has evolved into a comprehensive platform for RNA 2D visualisation, accessible athttps://r2dt.bio.
Iterative sacrificial 3D printing and polymer casting to create complex vascular grafts and multi-compartment bioartificial organs
Authors: Brassard Jonathan A. , Dharmaraj Saleth Sidharthan , Orimi Hamid Ebrahimi , Vdovenko Daria , Rioux Yannick , Wang Hanwen , Champion Kurtis , Lemaire Florent , Moeun Brenden N. , Zhao Jia , Liang Shenghui , Kieffer Timothy J. , Tchervenkov Jean I. , Soulez Gilles , Bégin-Drolet André , Ruel Jean , Leask Richard L. , Paraskevas Steven , Hoesli Corinne A. 
Published: October 2024

ABSTRACTSeveral emerging strategies to engineer artificial organs employ 3D printing to create vascular templates to provide nutrients and oxygen to immobilized cells. Significant challenges emerge when considering clinical implementation such as immune rejection of allogeneic cell sources, as well as achieving adequate perfusion and integration with endogenous vasculature. We propose a method by which cell-laden hydrogels are molded around ready-made polymeric vascular templates created via 3D printing to create human-scale artificial organs with internal vasculature. We applied this technique to create bioartificial pancreas systems with up to 9 internal flow channels via sacrificial carbohydrate glass 3D printing, porogen-loaded polycarbonate polyurethane dip-coating, followed by casting cell-laden hydrogels around the vascular templates. We optimized porogen size and concentration to maximise the porosity of our scaffolds without compromising mechanical properties, resulting in suture retention strength and compliance respectively matching commercial vascular grafts and native vessels. Bioreactor perfusion studies showed survival and maturation of stem cell derived pancreatic islets without significant differences to traditional suspension culture protocols. Insulin response dynamics were rapid in response to a glucose challenge at the perfusion inlet. Transplantation of the devices as iliac arteriovenous shunts in nondiabetic pigs confirmed safety and patency. These results show promise for the development of an implantable vascularized pancreas for the treatment of type 1 diabetes and demonstrate how bioartificial organs with engineered vascular geometries can be designed for translational applications.
Quantitative phase imaging with temporal kinetics predicts hematopoietic stem cell diversity
Authors: Yogo Takao , Iwamoto Yuichiro , Becker Hans Jiro , Kimura Takaharu , Sugiyama-Finnis Ayano , Yokomizo Tomomasa , Suda Toshio , Ota Sadao , Yamazaki Satoshi 
Published: October 2024

AbstractInnovative identification technologies for hematopoietic stem cells (HSCs) have advanced the frontiers of stem cell biology. However, most analytical techniques capture only a single snapshot, disregarding the temporal context. A comprehensive understanding of the temporal heterogeneity of HSCs necessitates live-cell, real-time and non-invasive analysis. Here, we developed a prediction system for HSC diversity by integrating single-HSC ex vivo expansion technology with quantitative phase imaging (QPI)-driven machine learning. By analyzing single-cell kinetics with QPI, we discovered previously undetectable diversity among HSCs that snapshot analysis fails to capture. Our QPI-driven algorithm quantitatively evaluates the stemness of individual HSCs and incorporates temporal information to significantly improve prediction accuracy. This platform marks a paradigm shift from “identification” to “prediction”, enabling us to forecast HSC status by analyzing their past temporal kinetics.
Liver Sinusoidal Endothelial Cells and Laminin dictate cholangiocytes’ fate in chronic liver disease
Authors: Manco Rita , Moliterni Camilla , Neirynck Gauthier , De Rudder Maxime , Picalausa Corinne , Ducor Leana , Fraga Montserrat , Lemaigre Frédéric , Sempoux Christine , Dili Alexandra , Leclercq Isabelle A. 
Published: October 2024

SummaryIn chronic liver disease (CLD), hepatocyte senescence limits conventional regeneration, prompting an alternative regeneration mechanism through transdifferentiation of reactive cholangiocytes (or ductular reaction cells - DRs). Yet, this alone is insufficient to avoid liver failure and transplantation, highlighting the importance of a deeper understanding of the mechanism. We focused on the DRs microenvironment. We identified laminin as a crucial component of the extracellular matrix to maintain DRs in a biliary phenotype, preventing their differentiation into hepatocytes. Liver sinusoidal endothelial cells (LSEC) are the cells regulating laminin degradation around DRs. By preventing LSEC capillarization during CLD, we enhanced DR differentiation into hepatocytes. We also demonstrated this causality in human samples. This is the first time that a mechanism for DR-driven regeneration has been described.
Electromagnetic Stimulated Anisotropic Hydrogels for Guided Neuronal Morphogenesis
Authors: Jensen Bjarke Nørrehvedde , Tong Tong , Skovborg Grith , Zhang Yuge , Müller Christoph , Matthiesen Cecillie Linneberg , Eschen Jens Toft , Elbæk Kirstine Juul , Wang Yuting , Pallesen Lone Tjener , Seliktar Dror , Dong Mingdong , Vægter Christian Bjerggaard , Korshøj Anders Rosendal , Chen Menglin 
Published: October 2024

AbstractWhile electrical circuits are a fundamental part of neural activity, the soft microstructural extracellular environment plays a vital role in driving the morphogenesis of neurons. To leverage this, we combine a wireless electromagnetic neural stimulation system with anisotropic GelMA hydrogels to promote and guide neural morphogensis. We show that oriented GelMA hydrogels support anisotropic growth of dorsal root ganglion as potential peripheral neural guide conduit and promote the formation of hippocampal neurospheres networking along the fiber direction. The central nervous system has limited regeneration due to glial scar formation, the presence of the perineuronal network, and limited upregulation of growth-associated genes post traumatic injuries. The system was further tested on human cortical brain tissue where hydrogel microfilaments promoted neurite outgrowth in a white-matter-mimicking manner between two pieces of brain slices, opening the possibility of central neural tissue regeneration.
Treatment with carnosic acid attenuates the secretion of pro-inflammatory mast cell mediators following IL-33 activation
Authors: Crozier Robert W.E. , Masi Jordan T. , MacNeil Adam J. 
Published: October 2024

AbstractIL-33 is an alarmin cytokine, released upon cellular damage, that has gained significant attention as a regulator of inflammation in several pathologies, including allergy. Once released, IL-33 binds to and activates its cognate receptor ST2, leading to the activation of the classical inflammatory Myddosome signalosome in an array of cells, including mast cells. Our group has recently identified the polyphenol carnosic acid (CA), as a potent regulator of mast cell activation in the context of allergic inflammation. Due to the key role IL-33 plays in the enhancement of allergies and other mast cell-associated diseases, we sought to determine the inhibitory potential of CA in a model of IL-33-mediated mast cell activation. Bone marrow-derived mast cells were stimulated with IL-33 under potentiation of SCF and treated with CA in the presence or absence of an allergen co-stimulation. Here, it was determined that treatment with CA led to a reduction in early ROS production, which translated into a significant impairment in the release of pro-inflammatory cytokines IL-6, IL-13, TNF and chemokines CCL1, CCL2 and CCL3. Surprisingly however, it was determined that CA treatment increased signaling through Akt and NFκB protein phosphorylation, leading to increased gene expression ofIL6, IL13,andCCL3as well as increased intracellular concentrations of IL-6 and CCL3. Taken together, our data suggests treatment with CA impairs the release mechanisms of pro-inflammatory mediators following IL-33 activation, warranting further investigation into the versatile biological activity of CA toward advance our understanding of CA as a potential anti-inflammatory therapeutic.
Impact of early-life respiratory syncytial virus infection on cell type-specific airway DNA methylation
Authors: McKennan Chris , Newcomb Dawn C. , Berdnikovs Sergejs , Gebretsadik Tebeb , Ma Siyuan , Bacharier Leonard B. , Seibold Max A. , Anderson Larry J. , Gern James E. , Ober Carole , Hartert Tina 
Published: October 2024

AbstractRationaleInfection with respiratory syncytial virus (RSV) in early-life is associated with subsequent childhood respiratory disorders, but the mechanism for this association is unknown. We hypothesized that RSV-mediated alteration in airway DNA methylation (DNAm) may play a role.ObjectivesInvestigate the impact of early-life RSV infection on airway DNAm.MethodsOur study population consisted of children from the INSPIRE population-based birth cohort. Early-life infection with RSV was defined as infection not requiring clinical illness before age one year, ascertained through active and passive surveillance. Methylation was measured in DNA from nasal airway epithelial cells (NAECs) at ages two years (n=88) and six years (n=539). Bulk gene expression in NAECs was available in a subset of participants at age two years (n=54).In silicocell type deconvolution was used to infer cell type-specific associations in suprabasal, ciliated, and “other” cell types.Measurements and Main ResultsWe identified 164 CpGs in ciliated cells and seven CpGs in suprabasal cells whose cell type-specific DNAm at age two years was associated with early-life RSV infection. The seven associations in suprabasal cells were still present at age six years and the directions of association replicated inin vitroinfection of epithelial cells with RSV in air liquid interface cultures. DNAm levels at four of the seven CpGs identified in suprabasal cells correlated with the expression of their nearest genes in suprabasal cells, which included genes previously implicated in asthma-related diseases. The DNAm levels of these four CpGs and the expression of their nearest genes in suprabasal cells at age two years were also associated with recurrent wheezing at age four years.ConclusionsWe demonstrate epigenetic changes in airway progenitor cells of children who have had RSV infection in the first year of life are conserved over time, associated with subsequent wheeze, have functional relevance, and replicate inin vitroinfection in ALI cultures. Our study is the first to show that early-life RSV infection, as opposed to severe illness, alters DNAm levels at functionally and clinically relevant loci.
Integrating geospatial tools in mapping forest fire severity and burned areas in the Western Usambara Mountain Forests, Lushoto, Tanzania
Authors: Mkiwa Braison P. , Mauya Ernest W. , Jonas Justo N. , Mbeyale Gimbage E. 
Published: October 2024

AbstractDespite the numerous negative effects of tropical forest fires in Tanzania, the causes and effects remain insufficiently documented. This study aimed to develop an integrated approach of using geospatial tools and socio-economic data to assess and map forest fire burn severity in West Usambara Mountain Forests. Three approaches including Participatory Rural Appraisal (PRA), satellite image analysis, and direct observation were used to generate information on spatial and temporal forest fire severity. Findings revealed that agricultural activities (44.5%) and charcoal production (21.1%) are the primary causes of these fires. Burn severity maps were created using the differenced Normalized Burned Ratio (dNBR) index, and the combined high and low severity areas ranged from 32.120% to 20.31%. The differenced Normalized Difference Vegetation Index (dNDVI) maps showed the combined high and low severity areas of 36.30% to 21.10% of the total study sites respectively. Post-fire NDVI time series analyses revealed a sharp decrease from 0.21 to 0.36 in all burned areas, indicating significant vegetation loss. Therefore, this study demonstrated the potential of integrating Remote Sensing and Socio-economic aspects highlighting the need for improved forest fire management through sustainable practices that balance economic and ecological considerations, offering insights that can be upscaled to other forest areas for effective management.
Amyloid Beta Pathology Accelerates Alterations in the Visual Pathway of the 5xFAD Mouse
Authors: McCool Shaylah , Smith Jennie C. , Sladek Asia , Fan Shan , Van Hook Matthew J. 
Published: October 2024

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by the formation of amyloid beta plaques and neurofibrillary tangles that leads to decreased quality of life due to behavioral, motor, and cognitive impairments. Due to the widespread pathological nature of AD, many brain regions are affected by amyloid beta plaques including regions important for vision such as the lateral geniculate nucleus (LGN) of the thalamus which is critical for relaying signals from the retina to the primary visual cortex. Using a wide range of techniques including electrophysiological approaches,in vivoandex vivoimaging methods, and immunohistochemistry in a mouse model with progressing amyloidosis (5xFAD), the goal of this study was to determine whether AD-like pathology disrupts neuronal and synaptic structure and function in the visual system.In vivoelectroretinogram recordings revealed photoreceptor dysfunction in the 6- and 9-month-old 5xFAD mice, while optical coherence tomography indicated no changes in retinal thickness. In the dorsolateral geniculate nucleus (dLGN), the rodent homolog of the primate LGN, we identified decreased densities of retinal ganglion cell axon terminals and fewer thalamocortical (TC) neuron cell bodies. No detectable deficits in excitatory synaptic function or TC neuron dendritic structure were seen in the dLGN, and reflexive visual behavior was also found to be normal in the 5xFAD mice. These results indicate relatively modest amyloid-triggered dysfunction in these stages of the visual system suggesting that amyloid beta plaque formation may play only a small role in the visual system dysfunction seen in AD patients. These results may also point to potential compensatory mechanisms that preserve function of visual pathways in the 5xFAD visual system.