Faculty Bibliography
Searched for:
Department/Unit:Cell Biology
Total Results:
14297
Editorial commentary: The hot phases of arrhythmogenic cardiomyopathy: A burning issue [Editorial]
PMID: 41713668
ISSN: 1873-2615
CID: 6005162
Majocchi's Granuloma [Case Report]
PMID: 41700678
ISSN: 1533-4406
CID: 6004502
Structures of naked mole-rat, tuco-tuco, and guinea pig ribosomes-is rRNA fragmentation linked to translational fidelity?
Ribosomes are central to protein synthesis in all organisms. In mammals, the ribosome functional core is highly conserved. Remarkably, two rodent species, the naked mole-rat (NMR) and tuco-tuco, display fragmented 28S ribosomal RNA (rRNA), coupled with high translational fidelity and long lifespan. The unusual ribosomal architecture in the NMR and tuco-tuco has been speculated to be linked to high translational fidelity. Here, we show, by single-particle cryo-electron microscopy, that despite the fragmentation of their rRNA, NMR and tuco-tuco ribosomes retain their core functional architecture. Compared to ribosomes of the guinea pig, a phylogenetically related rodent without 28S rRNA fragmentation, ribosomes of NMR and tuco-tuco exhibit poorly resolved density for certain expansion segments. In contrast, the structure of the guinea pig ribosome shows high similarity to the human ribosome. Enhanced translational fidelity in the NMR and tuco-tuco may stem from subtle, allosteric effects in dynamics, linked to rRNA fragmentation.
PMID: 41603730
ISSN: 1362-4962
CID: 6003492
HDL Regulates TGFβ-Receptor Lipid Raft Partitioning, Restoring Contractile Features of Cholesterol-Loaded Vascular Smooth Muscle Cells
Many cells identified as macrophage-like in human and mouse atherosclerotic plaques are thought to be of vascular smooth muscle cell (VSMC) origin. We identified cholesterol-mediated down-regulation of TGFβ signaling in vitro in human (h)VSMCs by localization of TGFβ receptors in membrane lipid rafts, which was reversed by high-density lipoprotein (HDL)-mediated cholesterol efflux. This restored VSMC contractile marker (Acta2) and suppressed macrophage marker (CD68) expression by promoting TGFβ enhancement of Mir145 expression. In vivo, administration of ApoA1 (which forms HDL) to atherosclerotic mice also promoted VSMC Acta2 expression and reduced CD68 expression. Because macrophage-like VSMCs are thought to have adverse properties, our studies not only show mechanistically how cholesterol causes their transition, but also suggest that efflux-competent HDL particles may have a therapeutic role by restoring a more favorable phenotypic state of VSMCs in atherosclerotic plaques.
PMID: 41687341
ISSN: 2452-302x
CID: 6002622
Compressed sensing-based approach identifies modular neural circuitry driving learned pathogen avoidance
An animal's survival hinges on its ability to integrate past information to modify future behavior. The nematode Caenorhabditis elegans adapts its behavior based on prior experiences with pathogen exposure, transitioning from attraction to avoidance of the pathogen. A systematic screen for the neural circuits that integrate the information of previous pathogen exposure to modify behavior has not been feasible because of the lack of tools for neuron type-specific perturbations. We overcame this challenge using methods based on compressed sensing to efficiently determine the roles of individual neuron types in learned avoidance behavior. Our screen revealed that distinct sets of neurons drive exit from lawns of pathogenic bacteria and prevent lawn re-entry. Using calcium imaging of freely behaving animals and optogenetic perturbations, we determined the neural dynamics that regulate one key behavioral transition after infection: stalled re-entry into bacterial lawns. We find that key neuron types govern pathogen lawn-specific stalling but allow the animal to enter nonpathogenic Escherichia coli lawns. Our study shows that learned pathogen avoidance requires coordinated transitions in discrete neural circuits and reveals the modular structure of this complex adaptive behavioral response to infection.
PMID: 41666040
ISSN: 2050-084x
CID: 6001952
Non-coding RNAs in lipid metabolism and their roles in atherosclerosis
The discovery of non-coding RNAs has expanded our understanding of how genetic features are linked to cellular function. The illumination of this so-called dark matter of the genome has revealed new categories of RNA with essential roles in the regulation of protein-coding genes and genome organization. In particular, microRNAs and long non-coding RNAs have emerged as important regulators of cardiovascular health and disease. In this Review, we summarize our current understanding of the mechanisms and functional roles of microRNAs and long non-coding RNAs in the regulation of lipid homeostasis, vascular biology and atherosclerosis. We discuss how interruption of non-coding RNA regulatory circuits influence lipoprotein metabolism in the liver and the circulation, as well as the effects of non-coding RNAs on inflammatory processes in the artery wall that contribute to atherosclerotic plaque formation. Finally, we highlight potential opportunities to harness non-coding RNAs as biomarkers and targeted therapeutics for atherosclerotic cardiovascular disease.
PMID: 41478885
ISSN: 1759-5010
CID: 6001262
Synovial Fluid Biomarkers in the Contralateral Knee Predict Patient-Reported Outcomes After Injury at Long-term Follow-up
BACKGROUND:Inflammatory biomarkers in an injured knee have been shown to predict outcomes, yet the role of the subsequent systemic inflammatory response to injury remains poorly understood. PURPOSE/OBJECTIVE:To investigate whether synovial fluid (SF) biomarkers from the contralateral uninjured knee could predict long-term patient-reported outcomes (PROs) for the operative knee in patients undergoing arthroscopic knee surgery. STUDY DESIGN/METHODS:Case series; Level of evidence, 4. METHODS:This retrospective analysis included patients undergoing knee SF aspiration before arthroscopy with ≥8 years of follow-up. SF was aspirated from both the injured and healthy contralateral knees, and concentrations of 10 pro- and anti-inflammatory biomarkers were quantified. Patients completed visual analog scale (VAS) for pain score, Lysholm, Tegner, and Knee injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS) surveys preoperatively and at the final follow-up. Stepwise linear regression was performed to identify the most significant predictor(s) of PRO scores utilizing log-normalized contralateral biomarker concentration, age, body mass index, injury type, and Outerbridge grade as covariates. Concentrations from the contralateral knee were also compared with the injured knee to assess for correlations. RESULTS:= .006) score at the final follow-up. Contralateral concentrations of monocyte chemotactic protein 1, macrophage inflammatory protein 1β, vascular endothelial growth factor, and TIMP-1 were correlated with levels in the operative knee but at significantly lower concentrations. CONCLUSION/CONCLUSIONS:SF biomarker levels in the contralateral uninjured knee at the time of arthroscopy were predictive of long-term outcomes for the operative knee. Increased levels of pro-inflammatory biomarkers were predictive of worse outcomes, while anti-inflammatory cytokines predicted improved scores. These results suggest that unilateral knee injury can result in a broader systemic inflammatory response that influences long-term outcomes in patients.
PMID: 41626727
ISSN: 1552-3365
CID: 5999512
Establishing dermatopathology encyclopedia DermpathNet with Artificial Intelligence-Based Workflow
Accessing high-quality, open-access dermatopathology image datasets for learning and cross-referencing is a common challenge for clinicians and trainees. To establish a comprehensive open-access dermatopathology dataset for educational, cross-referencing, and machine-learning purposes, we employed a hybrid workflow to curate and categorize images from the PubMed Central (PMC) repository. We used specific keywords to extract relevant images, and classified them using a novel hybrid method that combined deep learning-based image modality classification with figure caption analyses. Validation on 651 manually annotated images demonstrated the robustness of our workflow, with an F-score of 89.6% for the deep learning approach, 61.0% for the keyword-based retrieval method, and 90.4% for the hybrid approach. We retrieved over 7,772 images across 166 diagnoses and released this fully annotated dataset, reviewed by board-certified dermatopathologists. Using our dataset as a challenging task, we found the current image analysis algorithm from OpenAI inadequate for analyzing dermatopathology images. In conclusion, we have developed a large, peer-reviewed, open-access dermatopathology image dataset, DermpathNet, which features a semi-automated curation workflow.
PMID: 41651886
ISSN: 2052-4463
CID: 6000722
A targetable developmental program co-regulates angiogenesis and immune evasion in melanoma
Ultraviolet (UV)-induced DNA mutations generate genetic drivers of cutaneous melanoma and numerous neoantigens that can trigger anti-tumor immunity. Melanoma cells must therefore rapidly evade immune detection by modulating cell-autonomous epigenetic mechanisms and tumor-microenvironment interactions. Although angiogenesis typically facilitates immune infiltration, solid tumors increase vascularization while limiting immune cell entry. By comparing transcription factor (TF) expression across early-stage melanoma, naevi, and other cancers, we found that the homeodomain TF HOXD13 drives a melanoblast-like program upregulated in melanoma and strongly correlated with angiogenesis and immune cell exclusion. Using transcriptomics, 3D chromatin profiling, and in vivo models, we show that HOXD13 promotes tumor growth by enhancing angiogenesis and suppressing T-cell infiltration. HOXD13 orchestrates 3D enhancer-promoter contacts activating VEGFA, SEMA3A, and CD73, which remodel vasculature and elevate immunosuppressive adenosine. Consistently, HOXD13-induced tumor growth is reversed by combined VEGFR and adenosine receptor (AdR) inhibition, revealing a dual pro-angiogenic and immunosuppressive HOXD13 axis with therapeutic relevance.
PMID: 41631877
ISSN: 2159-8290
CID: 5999692
The International Guideline for the Definition, Classification, Diagnosis and Management of Urticaria
This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA2LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
PMID: 41649409
ISSN: 1398-9995
CID: 6000592
