9 research outputs found

    Hedging for Better Bets: Power Shifts, Credible Signals, and Preventive Conflict

    No full text
    10.1177/0022002718772349Journal of Conflict Resolutio

    Lack of Primary Cilia Primes Shear-Induced Endothelial-to-Mesenchymal Transition

    No full text
    Rationale: Primary cilia are cellular protrusions that serve as mechanosensors for fluid flow. In endothelial cells (ECs), they function by transducing local blood flow information into functional responses, such as nitric oxide production and initiation of gene expression. Cilia are present on ECs in areas of low or disturbed flow and absent in areas of high flow. In the embryonic heart, high-flow regime applies to the endocardial cushion area, and the absence of cilia here coincides with the process of endothelial-to-mesenchymal transition (EndoMT). Objective: In this study, we investigated the role of the primary cilium in defining the responses of ECs to fluid shear stress and in EndoMT. Methods and Results: Nonciliated mouse embryonic ECs with a mutation in Tg737/Ift88 were used to compare the response to fluid shear stress to that of ciliated ECs. In vitro, nonciliated ECs undergo shear-induced EndoMT, which is accompanied by downregulation of Klf4. This Tgf beta/Alk5-dependent transformation is prevented by blocking Tgf beta signaling, overexpression of Klf4, or rescue of the primary cilium. In the hearts of Tg737(orpk/orpk) embryos, Tgf beta/Alk5 signaling was activated in areas in which ECs would normally be ciliated but now lack cilia because of the mutation. In these areas, ECs show increased Smad2 phosphorylation and expression of alpha-smooth muscle actin. Conclusions: This study demonstrates the central role of primary cilia in rendering ECs prone to shear-induced activation of Tgf beta/Alk5 signaling and EndoMT and thereby provides a functional link between primary cilia and flow-related endothelial performance. (Circ Res. 2011;108:1093-1101.)Signal transduction in aging related disease

    KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome

    Get PDF
    Contains fulltext : 152408.pdf (publisher's version ) (Open Access)BACKGROUND: Joubert syndrome (JBTS) and related disorders are defined by cerebellar malformation (molar tooth sign), together with neurological symptoms of variable expressivity. The ciliary basis of Joubert syndrome related disorders frequently extends the phenotype to tissues such as the eye, kidney, skeleton and craniofacial structures. RESULTS: Using autozygome and exome analyses, we identified a null mutation in KIAA0556 in a multiplex consanguineous family with hallmark features of mild Joubert syndrome. Patient-derived fibroblasts displayed reduced ciliogenesis potential and abnormally elongated cilia. Investigation of disease pathophysiology revealed that Kiaa0556 (-/-) null mice possess a Joubert syndrome-associated brain-restricted phenotype. Functional studies in Caenorhabditis elegans nematodes and cultured human cells support a conserved ciliary role for KIAA0556 linked to microtubule regulation. First, nematode KIAA0556 is expressed almost exclusively in ciliated cells, and the worm and human KIAA0556 proteins are enriched at the ciliary base. Second, C. elegans KIAA0056 regulates ciliary A-tubule number and genetically interacts with an ARL13B (JBTS8) orthologue to control cilium integrity. Third, human KIAA0556 binds to microtubules in vitro and appears to stabilise microtubule networks when overexpressed. Finally, human KIAA0556 biochemically interacts with ciliary proteins and p60/p80 katanins. The latter form a microtubule-severing enzyme complex that regulates microtubule dynamics as well as ciliary functions. CONCLUSIONS: We have identified KIAA0556 as a novel microtubule-associated ciliary base protein mutated in Joubert syndrome. Consistent with the mild patient phenotype, our nematode, mice and human cell data support the notion that KIAA0556 has a relatively subtle and variable cilia-related function, which we propose is related to microtubule regulation

    Cilia in cell signaling and human disorders

    No full text

    Sex-biased survival and philopatry in birds: Do they interact?

    No full text

    Mathematical Models of Pattern Formation in Planktonic Predation-Diffusion Systems: A Review

    No full text

    Acanthamoeba Keratitis: Current Status and Urgent Research Priorities

    No full text
    corecore