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Demidov, V.

Publications and source records attributed to Demidov, V..

2 recordsLinked to original sources

Differentiation of semi-transparent tissue phantom inclusions using optical coherence tomography towards label-free neurography and lymphography

SignificanceLymphatic and peripheral nervous system imaging is of prime importance for monitoring various important pathologic processes including cancer development, metastasis, and response to therapy. AimOptical coherence tomography (OCT) is a promising approach for this imaging task but is challenged by the near-transparent nature of these structures. Our aim is to detect and differentiate semi-transparent materials using OCT texture analysis, towards label-free neurography and lymphography. ApproachWe have recently demonstrated a novel OCT texture analysis-based approach that used speckle statistics to image lymphatics and nerves in-vivo that does not rely on negative contrast. However, these two near-transparent structures could not be differentiated from each other easily in the texture analysis parameter space. Here we perform a rigorous follow-up study to improve upon this differentiation in controlled phantoms mimicking the optical properties of these tissues. ResultsThe results of the three-parameter Rayleigh distribution fit to the OCT images of six types of tissue-mimicking materials varying in transparency and biophysical properties demonstrate clear differences between them, suggesting routes for improved lymphatics-nerves differentiation. ConclusionsWe demonstrate a novel OCT texture analysis based lymphatics-nerves differentiation methodology in tissue-simulating phantoms. Future work will focus on in-vivo lymphangiography and neurography studies of longitudinal treatment monitoring for therapy feedback and optimization.

cancer biology↗

CLASP2 stabilizes GDP-associated terminal tubulins to prevent microtubule catastrophe

CLASPs are ubiquitous stabilizers of microtubule dynamics but their molecular targets at the microtubule plus-end are not understood. Using DNA origami-based reconstructions we show that clusters of human CLASP2 form a load-bearing bond with terminal GDP-tubulins at the stabilized microtubule tip. This activity relies on the unconventional TOG2 domain of CLASP2, which releases its high-affinity bond with the GDP-dimers upon their conversion into polymerization-competent GTP-tubulin. By tethering dynamic microtubule ends near immobilized CLASP2, we show that the targets for CLASP2 binding at the polymerizing tip arise stochastically, leading to nanoscale disruptions in microtubule tip integrity. The ability of CLASP2 to recognize nucleotide-specific tubulin conformation and stabilize the catastrophe-promoting GDP-tubulins intertwines with the previously underappreciated exchange between GDP and GTP at terminal tubulins, providing a distinct molecular mechanism to suppress microtubule catastrophe without affecting tubulin incorporation.

biophysics↗