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Open AccessCells in the polyaneuploid cancer cell (PACC) state have increased metastatic potential
Although metastasis is the leading cause of cancer deaths, it is quite rare at the cellular level. Only a rare subset of cancer cells (~ 1 in 1.5 billion) can complete the entire metastatic cascade: invasion, ...
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Article
Open AccessSelective Signal Capture from Multidimensional GPCR Outputs with Biased Agonists: Progress Towards Novel Drug Development
G protein coupled receptors (GPCRs) are a superfamily of transmembrane-spanning receptors that are activated by multiple endogenous ligands and are the most common target for agonist or antagonist therapeutics...
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Article
Open AccessPGC1/PPAR drive cardiomyocyte maturation at single cell level via YAP1 and SF3B2
Cardiomyocytes undergo significant structural and functional changes after birth, and these fundamental processes are essential for the heart to pump blood to the growing body. However, due to the challenges o...
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Article
Open AccessFFAR1 activation attenuates histamine-induced myosin light chain phosphorylation and cortical tension development in human airway smooth muscle cells
Activation of free fatty acid receptors (FFAR1 and FFAR4) which are G protein-coupled receptors (GPCRs) with established (patho)physiological roles in a variety of obesity-related disorders, induce human airwa...
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Article
A microphysiological model of the bronchial airways reveals the interplay of mechanical and biochemical signals in bronchospasm
In asthma, the contraction of the airway smooth muscle and the subsequent decrease in airflow involve a poorly understood set of mechanical and biochemical events. Organ-level and molecular-scale models of the...
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Article
Open AccessBiomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread
The root cause of cancer mortality and morbidity is the metastatic spread of the primary tumor, but underlying mechanisms remain elusive. Here we investigate biomechanical interactions that may accompany invas...
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Article
Open AccessTGFβ1 reinforces arterial aging in the vascular smooth muscle cell through a long-range regulation of the cytoskeletal stiffness
Here we report exquisitely distinct material properties of primary vascular smooth muscle (VSM) cells isolated from the thoracic aorta of adult (8 months) vs. aged (30 months) F344XBN rats. Individual VSM cells d...
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Article
Open AccessAIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination
A defining hallmark of primary and metastatic cancers is the migration and invasion of malignant cells. These invasive properties involve altered dynamics of the cytoskeleton and one of its major structural co...
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Article
Open AccessRole of differentially expressed microRNA-139-5p in the regulation of phenotypic internal anal sphincter smooth muscle tone
The present study focused on the role of microRNA-139-5p (miRNA-139-5p) in the regulation of basal tone in internal anal sphincter (IAS). Applying genome-wide miRNA microarrays on the phenotypically distinct s...
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Article
Open AccessDefining an olfactory receptor function in airway smooth muscle cells
Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant ...
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Article
Directed migration of cancer cells guided by the graded texture of the underlying matrix
Living cells and the extracellular matrix (ECM) can exhibit complex interactions that define key developmental, physiological and pathological processes. Here, we report a new type of directed migration—which ...
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Reply to: Activation of BK channels may not be required for bitter tastant–induced bronchodilation
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Open AccessA novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening
A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a nov...
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Bronchodilator activity of bitter tastants in human tissue
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Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction
G protein-coupled receptor (GPCR)-mediated increases in intracellular calcium generally lead to constriction of airway smooth muscle. Deshpande et al. find that bitter taste receptors, another class of GPCRs, are...
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Article
Universal physical responses to stretch in the living cell
How do cells in our body go about their routine mechanical business of stretching, contracting and remodelling? This question has far-reaching implications for understanding airway narrowing in asthma, cell in...
