37 research outputs found
Oncometabolite induced primary cilia loss in pheochromocytoma
Primary cilia are sensory organelles involved in regulation of cellular signaling. Cilia loss is frequently observed in tumors; yet, the responsible mechanisms and consequences for tumorigenesis remain unclear. We demonstrate that cilia structure and function is disrupted in human pheochromocytomas – endocrine tumors of the adrenal medulla. This is concomitant with transcriptional changes within cilia-mediated signaling pathways that are associated with tumorigenesis generally and pheochromocytomas specifically. Importantly, cilia loss was most dramatic in patients with germline mutations in the pseudohypoxia-linked genes SDHx and VHL. Using a pheochromocytoma cell line derived from rat, we show that hypoxia and oncometabolite-induced pseudohypoxia are key drivers of cilia loss and identify that this is dependent on activation of an Aurora-A/HDAC6 cilia resorption pathway. We also show cilia loss drives dramatic transcriptional changes associated with proliferation and tumorigenesis. Our data provide evidence for primary cilia dysfunction contributing to pathogenesis of pheochromocytoma by a hypoxic/pseudohypoxic mechanism and implicates oncometabolites as ciliary regulators. This is important as pheochromocytomas can cause mortality by mechanisms including catecholamine production and malignant transformation, while hypoxia is a general feature of solid tumors. Moreover, pseudohypoxia-induced cilia resorption can be pharmacologically inhibited, suggesting potential for therapeutic intervention
Recognition and position estimation of 3D objects from range images using algebraic and movement invariants
Performance verification of the anisotropic diffusion technique for range image smoothing
Time-of-flight optical ranging system based on time-correlated single-photon counting
The design and implementation of a prototype time-of-flight optical ranging system based on the time-correlated single-photon-counting technique are described. The sensor is characterized in terms of its longitudinal and transverse spatial resolution, single-point measurement time, and long-term stability. The system has been operated at stand-off distances of 0.5–5 m, has a depth repeatability of <30 μm, and has a lateral spatial resolution of <500 μm