bluuebunny/crossref_metadata_2025_split huggingface dataset:
VPS28 regulates triglyceride synthesis and is mediated by the ubiquitination pathway in a bovine mammary epithelial cell line and mouse model
Authors: Liu Lily , Wang Jinhai , Zheng Xianrui , Zhang Qin 
Published: July 2024

AbstractVPS28 (vacuolar protein sorting 28) is a subunit of the endosomal sorting complexes required for transport (ESCRTs), and is involved in ubiquitination. Ubiquitination is a crucial system for protein degradation in eukaryotes. Considering the recent findings on the role of ubiquitination in regulating lipid metabolism, we hypothesized that VPS28 might affect the expression of genes involved in milk fat synthesis. To test this hypothesis, we modulated VPS28 expression in the bovine mammary epithelial cell (MAC-T) line and measured the effects on triglyceride (TG) synthesis using lentivirus-mediated techniques. The results indicated that VPS28 knockdown significantly upregulated the fatty acid transporter CD36 (CD36 molecule) and the adipose differentiation-related protein (ADFP), leading to increased TG and fatty acid production, alongside elevated expression of ubiquitin (UB) protein and reduced proteasome activity. In contrast, VPS28 overexpression increased CD36 levels without significantly affecting ADFP and TG levels, showing a trend toward reduced lipid droplets and increased UB expression and proteasome activity. Furthermore, the inhibition of the ubiquitin-proteasome system and endosomal-lysosomal pathway using epoxomicin and chloroquine, respectively, resulted in a further elevation of CD36, ADFP, and TG levels, thereby enhancing cell viability. These in vitro findings were validated in vivo by a mouse model, where VPS28 knockdown enhanced CD36, ADFP, UB expression, TG content, and lipid droplets in mammary glands, without pathological changes in mammary tissue or blood TG alterations. These results confirm the pivotal role of VPS28 in regulating TG synthesis via the ubiquitination pathway, offering novel insights into the molecular mechanisms of milk fat production in a bovine in vitro cell model.
Early-life Microbiome-Derived HCA Enhances Type 3 Immunity via FXR- dependent m6A RNA methylation
Authors: Yang Zhipeng , Lin Zhiyuan , You Yaojie , Zhang Mei , Gao Ning , Wang Xinru , Peng Jian , Wei Hongkui 
Published: July 2024

AbstractThe gut microbiome plays a crucial role in the development of intestinal immunity during early life, but the underlying mechanisms remain largely unknown. Here, we found oxygen consumption in neonatal rats byS. boulardiiaccelerated the colonization of the microbiome and the development of type 3 immunity, which protected againstS. typhimurium. Microbiome maturation increased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and elevated the levels of Hyocholic acid (HCA). HCA promotes the development of γδT and type 3 innate lymphoid cell (ILC3) by sustaining the stability ofRorcmRNA via the FXR-WTAP- N6-methyl-adenosine (m6A) axis.L. reuteri, a bacterium encoding BSH, was enriched by oxygen consumption in the intestine and promoted intestinal type 3 immunity. However, inhibition of BSH blocks theL. reuteri-induced development of intestinal type 3 immunity. These results reveal the role of microbiome-derived HCA in the regulation of intestinal type 3 immunity during early life.
Comprehensive Phenotyping of Extracellular Vesicles in Blood of Healthy Humans – Insights into Cellular Origin and Biological Variability
Authors: Holcar Marija , Marić Ivica , Tertel Tobias , Goričar Katja , Primožič Urška Čegovnik , Černe Darko , Giebel Bernd , Lenassi Metka 
Published: July 2024

AbstractDespite immense interest in biomarker applications of extracellular vesicles (EVs) from blood, our understanding of their physiological population in healthy humans remains limited. Using imaging and multiplex bead-based flow cytometry, we comprehensively quantified circulating EVs with respect to their cellular origin in a large cohort of healthy blood donors. We assessed coefficients of variations to characterise their biological variability and explored demographic, clinical, and lifestyle factors contributing to this variability. Cell-specific circulating EV subsets show a wide range of concentrations, which do not directly reflect concentrations of blood cells, indicating diverse patterns of EV subset release and/or uptake, even for EVs originating from the same cell type. Interestingly, tetraspanin+ circulating EVs largely originate from platelets and to a lesser extent from lymphocytes. PCA and association analyses demonstrate high biological inter-individual variability in circulating EVs across healthy humans, which can be only partly explained by the influence of sex, menopausal status, age and smoking on specific circulating EV and/or tetraspanin+ circulating EV subsets. No global influence of the explored subject’s factors on circulating EVs was detected. Our findings provide the first comprehensive, quantitative data towards the cell-origin atlas of blood EVs, with important implications in the clinical use of EVs as biomarkers of disease.
Distinct modes of holobiont specialization among cryptic coral lineages
Authors: Grupstra Carsten G.B. , Meyer-Kaiser Kirstin S. , Bennett Matthew-James , Andres Maikani O. , Juszkiewicz David J. , Fifer James E. , Da-Anoy Jeric P. , Gomez-Campo Kelly , Martinez-Rugerio Isabel , Aichelman Hannah E. , Huzar Alexa K. , Hughes Annabel M. , Rivera Hanny E. , Davies Sarah W. 
Published: July 2024

AbstractAs ocean warming threatens reefs worldwide, identifying corals with adaptations to higher temperatures is critical for conservation. Genetically distinct but morphologically similar (i.e.,cryptic) coral populations can be specialized to extreme habitats and thrive under stressful conditions. These corals often associate with locally beneficial microbiota (Symbiodiniaceae photobionts and bacteria), clouding interpretation of the drivers of thermal tolerance. Here, we leverage a holobiont (massivePorites) with high host-partner fidelity to investigate adaptive variation across classic (“typical” conditions) and extreme reefs characterized by higher temperatures and light attenuation. We uncovered three cryptic lineages that exhibit limited micro-morphological variation; one lineage dominated classic reefs (L1), one had more even distributions (L2), and a third was restricted to extreme reefs (L3). Two lineages were more closely related to populations ∼4300 km away, suggesting that these lineages are widespread. All corals harboredCladocopiumC15 photobionts, but strain-level compositions differed among lineages and reef types. L1 associated with distinct photobionts and bacteria in each reef type, whereas L2 had relatively stable associations. L3 hosted unique photobiont strains, signaling high host-photobiont fidelity. Analysis of light harvesting capacity and thermal tolerance revealed key adaptive variation underpinning survival in distinct habitats. L1 had the highest light absorption efficiency and lowest thermal tolerance, suggesting it is a classic reef specialist. L3 had the lowest light absorption efficiency and the highest thermal tolerance, showing that it is an extreme reef specialist. L2 had intermediate light absorption efficiency and thermal tolerance, signaling habitat generalism, potentially explaining how it survives well in both habitat types. These findings reveal diverging holobiont strategies to cope with extreme conditions. Resolving coral lineages is key to understanding variation in thermal tolerance among coral populations; uncovering thermally-tolerant holobionts can strengthen our understanding of coral evolution and symbiosis, and support global conservation and restoration efforts.
The functional roles of zebrafishHoxA- andHoxD-related clusters in the pectoral fin development
Authors: Ishizaka Mizuki , Maeno Akiteru , Nakazawa Hidemichi , Fujii Renka , Oikawa Sae , Tani Taisei , Kanno Haruna , Koita Rina , Kawamura Akinori 
Published: July 2024

AbstractThe paralogs 9-13Hoxgenes in mouseHoxAandHoxDclusters are critical for limb development. When bothHoxAandHoxDclusters are deleted in mice, significant limb truncation is observed compared to the phenotypes of single and compound mutants ofHox9-13genes in these clusters. In zebrafish, mutations inhox13genes inHoxA- andHoxD-related clusters result in abnormal morphology of pectoral fins, homologous to forelimbs. However, the effect of the simultaneous deletions of entireHoxA- andHoxD-related clusters on pectoral fin development remains unknown. Here, we generated mutants with several combinations ofhoxaa,hoxab, andhoxdacluster deletions and analyzed the pectoral fin development. Inhoxaa-/-;hoxab-/-;hoxda-/-larvae, the endoskeletal disc and the fin-fold are significantly shortened in developing pectoral fins. In addition, we show that this anomaly is due to defects in the pectoral fin growth after the fin bud formation. Furthermore, in the surviving adult mutants, micro-CT scanning reveals defects in the posterior portion of the pectoral fin which is thought to represent latent regions of the limb. Our results further support that the functional role ofHoxAandHoxDclusters is conserved in the paired appendage formation in bony fishes.
Cellular heterogeneity in hypertrophic burn scars in response to carbon dioxide laser therapy
Authors: Chen Yung-Yi , Mahony Christopher , Turner Jason , Smith Charlotte M , Abdulsalam Abdulrazak , Amirize Ezekwe , Prince Amberley , Heagerty Adrian , Roberts Claudia , Croft Adam , Wilson Yvonne , Moiemen Naiem , Lord Janet M 
Published: July 2024

AbstractFractional carbon dioxide (AFCO2) laser therapy is used for treating pathological scarring, but the clinical outcomes are variable and the mechanisms of scar reduction poorly understood. We investigated the mechanisms underpinning efficacy of AFCO2laser therapy, performing single-cell RNA sequencing in skin biopsies from patients with hypertrophic scars after AFCO2laser therapy. Patients with younger scars (Good Responder, GR, <6 years from healing) had better scar reduction than patients with older scars (Poor Responder, PR, >6 years from healing) by various measures of scarring. scRNAseq analysis revealed that genes enriched in GR were associated with extracellular matrix and structure organisation (COL14A1,POSTN,SPARC); whereas genes enriched in PR were related to enhanced immune responses (IL-12,MSTN, HLA-DQA). The groups had distinct intercellular communication networks and differentiation trajectories after AFCO2, with regenerative Mesenchymal fibroblasts associated with a good response and inflammatory Secretory Papillary and Inflammatory Fibroblasts with a poor response.
3D Printed Multifunctional Bioadhesive Patch with Intrinsic Bioelectronic Properties for Decoding Electromechanical and Anisotropic Cardiac Microenvironment
Authors: Dutta Sayan Deb , Patil Tejal V. , Lim Ki-Taek 
Published: July 2024

ABSTRACTFabricating anisotropic multifunctional bioadhesive patches with tunable mechanical stiffness, electrical conductivity, antimicrobial activity, and modulating cellular behavior is crucial for the successful management of cardiac tissue injury and boosting immunogenic microenvironments. Direct ink writing (DIW)-based 3D printing holds tremendous potential for developing electroactive cardiac patches (ECPs) with anisotropic microarchitecture. Inspired by the native myocardium, we developed a multifunctional and anisotropic ECP with tunable stiffness by incorporating a highly conductive graphene oxide/nanodiamond (GO@ND) complex into a biocompatible carboxymethyl chitosan/polyvinyl alcohol (CSA) matrix for regulating immunogenic and cardiomyogenic cues. The incorporation of GO@ND enhanced the electrical conductivity (∼22.6 S mm-1) with high interfacial toughness (>250 MJ m-1) and improved the printability (n= 0.5) with concentration-dependent self-assembly into the CSA matrix. We observed that electrical stimulation (EFs; 250 mV/20 min/day) through nanoengineered CSA resulted in broad-spectrum antibacterial activity againstE. coliandS. aureusby 99.29% and 98.74%, respectively, via sustained release of curcumin (Cur). Moreover, the electromechanical study revealed that CSA with higher stiffness (∼6.2 kPa) activated cytoplasmic YAPs during macrophage polarization. Besides, stiffness and EFs regulated human cardiomyocyte differentiation through anisotropic force-driven early activation of Vinculin, triggering the phosphorylation of NFATc3 and activating Lamin A/C in a YAP-dependent manner. Based on these findings, we anticipated that the fabricated nanoengineered patch had tremendous potential for regulating the electro-cardiomyogenic microenvironment with multifunctional abilities.
An ecological-evolutionary perspective on the genomic diversity and habitat preferences of the Acidobacteriota
Authors: McReynolds Ella , Elshahed Mostafa S. , Youssef Noha H. 
Published: July 2024

AbstractMembers of the phylum Acidobacteriota inhabit a wide range of ecosystems including soils. We analyzed the global patterns of distribution and habitat preferences of various Acidobacteriota lineages across major ecosystems (soil, engineered, host-associated, marine, non-marine saline and alkaline, and terrestrial non-soil ecosystem) in 248,559 publicly available metagenomic datasets. Classes Terriglobia, Vicinamibacteria, Blastocatellia, and Thermoanaerobaculia were highly ubiquitous and showed clear preference to soil over non-soil habitats, class Polarisedimenticolia showed comparable ubiquity and preference between soil and non-soil habitats, while classes Aminicenantia and Holophagae showed preferences to non-soil habitats. However, while specific preferences were observed, most Acidobacteriota lineages were habitat generalists rather than specialists, with genomic and/or metagenomic fragments recovered from soil and non-soil habitats at various levels of taxonomic resolution. Comparative analysis of 1930 genomes strongly indicates that phylogenetic affiliation plays a more important role than the habitat from which the genome was recovered in shaping the genomic characteristics and metabolic capacities of theAcidobacteriota. The observed lack of strong habitat specialization and habitat transition driven lineage evolution in the Acidobacteriota suggest ready cross colonization between soil and non-soil habitats. We posit that such capacity is key to the successful establishment of Acidobacteriota as a major component in soil microbiomes post ecosystem disturbance events or during pedogenesis.
SOX21 suppresses GBM growth by repressing AP-1 regulated target genes
Authors: Rrapaj Eltjona , Yuan Juan , Kurtsdotter Idha , Misyurin Vsevolod , Baselli Guido , Persson Oscar , Bergsland Maria , Muhr Jonas 
Published: July 2024

AbstractResistance of glioblastoma stem cells (GSCs) to standard treatments is a major cause of glioblastoma (GBM) recurrence. This study examines the potential of the transcription factor SOX21 to inhibit GSC properties and combat GBM progression. Results show that increasing SOX21 levels in primary GSCs induces an anti-tumorigenic gene expression profile, which is substantiated by a significant correlation between high SOX21 expression and improved survival rates of GBM patients. Furthermore, induced SOX21 expression in pre-established GBM reduces tumor growth and significantly extends the survival of orthotopically transplanted mice. SOX21 acts as a tumor suppressor by binding to and epigenetically repressing AP-1-targeted chromatin, thereby downregulating adjacent genes. Consistently, the anti-tumorigenic activities of SOX21 are replicated by small molecules that inhibit AP-1 activity, whereas overexpression of an AP-1 transcription factor reverses these effects. Overall, this research demonstrates the potent role of SOX21 in restricting GBM progression through repression of AP-1-stimulated tumor-promoting gene expression.
PD-1 blockade enhances HIV-1 vaccine-induced CD8⁺ T-cell responses in PWH early ART-treated
Authors: Marin Miguel , Ruiz Alba , Jimenez-Moyano Esther , Ouchi Dan , Blanch-Lombarte Oscar , Peña Ruth , Gorman Dan , Barnard Richard , Hanke Tomas , Clotet Bonaventura , Howell Bonnie , Brander Christian , Mothe Beatriz , Prado Julia G 
Published: July 2024

AbstractCurrent HIV-1 therapeutic vaccines do not generate T-cell immune responses in people with HIV-1 (PWH) able to eradicate the virus or to broadly control viral replication. The expression of inhibitory receptors (IRs) may limit vaccine efficacy by reducing specific effector functions in vaccine-induced T-cells. Recently, the clinical use of antibodies targeting IRs or immune checkpoint blockade (ICB) has demonstrated remarkable success in cancer remission. Therefore, there is a potential benefit of using ICB in PWH to improve the effectiveness of vaccine-induced T-cell responses. Here, we evaluated functional changes in vaccine-induced HIV-specific CD8⁺ T-cell responses by in-vitro PD-1 and TIM-3 blockade during immune stimulation in PWH early ART-treated and vaccinated (Etvac). We compared Etvac to PWH early ART-treated (Et) and chronic ART-treated PWH (Chro). Our results demonstrate a significant increase in the functional responses of vaccine-induced HIV-1-specific CD8⁺ T-cells upon PD-1 but not TIM-3 blockade in cellular proliferation, IFNγ production, and activation. Although no effect was found in Et, similar findings were obtained in HIV-1-specific CD8⁺ T-cells in Chro for combined PD-1/TIM-3 blockade. Moreover, we identify in Etvac a direct association between PD-1 expression in CD8+T cells and in vitro response to anti-PD-1 treatment. Our findings support the potential adjuvant effect of PD-1 blockade to improve HIV-1 therapeutic vaccine efficacy in early ART-treated PWH for future human studies.
Evolutionary new centromeres in the snowy owl genome putatively seeded from a transposable element
Authors: Baalsrud H. T. , Garmann-Aarhus B. , Enevoldsen E. L. G. , Krabberød A.K. , Fischer D. , Tooming-Klunderud A. , Skage M. , Árnyasi M. , Sandve S. R. , Jakobsen K.S. , Nielsen R. , Boessenkool S. , Tørresen O. K. 
Published: July 2024

AbstractComparative genomic studies in birds have revealed that bird genomes are relatively repeat-poor and stable in terms of karyotype, size, and gene synteny/collinearity compared to other vertebrates. One notable exception is the owls, with cytogenetic studies demonstrating large variations in karyotypes and the evolution of unusual centromeric satellite repeats in some species. However, there has so far not been an investigation into genome architecture and repeat landscape of owls. Here, we present a chromosome-level genome assembly for the snowy owl (Bubo scandiacus). We find that the repeat DNA content in the relatively large snowy owl genome (1.6 Gb) is among the highest reported for any bird genome to date (28.34% compared to an average of ∼10% in other birds). The bulk of the snowy owl genomic repeat landscape consists of centromeric satellite DNA, which appears to have originated from an endogenous retrovirus (ERV1). Using gene collinearity analyses we show that the position of these evolutionary new centromeres (ECNs) are not homologous with chicken centromeres, and are located in regions with collinearity breaks to other bird genomes due to chromosomal rearrangements. Our results support rapid transposable element-driven evolution of lineage-specific centromeres, which could have played a role in reproductive isolation and speciation of the snowy owl.
Brain virtual histology of a lizard species (Podarcis bocagei) using X-ray micro-tomography and deep-learning segmentation
Authors: Zhou Tunhe , Dragunova Yulia , Triki Zegni 
Published: July 2024

AbstractLately, there has been an emphasis on the importance of studying inter-individual variation in animal behaviour and cognition and understanding its underlying mechanisms. What was once considered mere noise around population mean can be explained by individual characteristics such as brain morphology and functionality. However, logistical limitations can be faced when studying the brain, especially for research involving wild animals, such as dealing with small sample sizes and time-consuming methods. Here, we combined an efficient and accurate method using X-ray micro-tomography and deep-learning (DL) segmentation to estimate the volume of six main brain areas of wild lizards,Podarcis bocagei: olfactory bulbs, telencephalon, diencephalon, midbrain, cerebellum and brain stem. Through quantitative comparison, we show that a sufficient deep-learning neural network can be trained with as few as five data sets. From this, we applied the trained deep-learning algorithm to obtain volume data of the six brain regions from 29 brains ofPodarcis bocagei. We provide a detailed protocol for our methods, including sample preparation, X-ray tomography, and 3D volumetric segmentation. Our work is open-access and freely available, with the potential to benefit researchers in various fields, such as animal physiology, biomedical studies, and computer sciences.
SYSTEMIC FRATAXIN DEFICIENCY CAUSES TISSUE-DEPENDENT IRON HOMEOSTASIS ALTERATIONS: IMPLICATIONS FOR FRIEDREICH ATAXIA
Authors: Pazos-Gil Maria , Medina-Carbonero Marta , Sanz-Alcázar Arabela , Portillo-Carrasquer Marta , Oliveira Luiza , Hernandez Gonzalo , Sánchez Mayka , Delaspre Fabien , Cabiscol Elisa , Ros Joaquim , Tamarit Jordi 
Published: July 2024

ABSTRACTFriedreich Ataxia (FA) is a cardio-neurodegenerative disease caused by mutations in the frataxin gene, which result in low frataxin expression. It is well-established that frataxin deficiency affects iron homeostasis, but the tissue-specificity of these alterations is poorly understood. In this study, we have analyzed iron homeostasis alterations in the FXNI151F mouse model, which presents systemic frataxin deficiency and neurological defects resembling FA patients. Iron overload is observed in the brain from 21-week old FXNI151F mice, both males and females, and it does not further accumulate in older animals. It is also observed in livers from 39-week old mutant females, but not in males. Iron signaling is altered in all tissues: in brain and liver Iron Regulatory Protein 1 (IRP1) content is decreased, while in heart increased IRP2 and decreased specific aconitase 2 activity are observed. Remarkably, these cardiac alterations are partially restored in 39- week-old animals, suggesting that the heart is activating an iron-deficiency response to compensate for deficient iron-sulfur biogenesis. Our findings demonstrate that frataxin deficiency affects iron homeostasis in a time dependent and tissue-specific manner, and that the pathological mechanisms in FA comprise both iron accumulation and limited iron availability. Understanding this specificity is crucial for the design of iron-related therapeutic interventions aiming to improve FA symptomatology.