Iskanje po katalogu digitalne knjižnice

Opis: Quantitative analysis of the vascular network anatomy is critical for the understanding of the vasculature structure and function. In this study, we have combined microcomputed tomography (microCT) and computational analysis to provide quantitative three-dimensional geometrical and topological characterization of the normal kidney vasculature, and to investigate how 2 core genes of the Wnt/planar cell polarity, Frizzled4 and Frizzled6, affect vascular network morphogenesis. Experiments were performed on frizzled4 (Fzd4-/-) and frizzled6 (Fzd6-/-) deleted mice and littermate controls (WT) perfused with a contrast medium after euthanasia and exsanguination. The kidneys were scanned with a high-resolution (16 μm) microCT imaging system, followed by 3D reconstruction of the arterial vasculature. Computational treatment includes decomposition of 3D networks based on Diameter-Defined Strahler Order (DDSO). We have calculated quantitative (i) Global scale parameters, such as the volume of the vasculature and its fractal dimension (ii) Structural parameters depending on the DDSO hierarchical levels such as hierarchical ordering, diameter, length and branching angles of the vessel segments, and (iii) Functional parameters such as estimated resistance to blood flow alongside the vascular tree and average density of terminal arterioles. In normal kidneys, fractal dimension was 2.07±0.11 (n = 7), and was significantly lower in Fzd4-/- (1.71±0.04; n = 4), and Fzd6-/- (1.54±0.09; n = 3) kidneys. The DDSO number was 5 in WT and Fzd4-/-, and only 4 in Fzd6-/-. Scaling characteristics such as diameter and length of vessel segments were altered in mutants, whereas bifurcation angles were not different from WT. Fzd4 and Fzd6 deletion increased vessel resistance, calculated using the Hagen-Poiseuille equation, for each DDSO, and decreased the density and the homogeneity of the distal vessel segments. Our results show that our methodology is suitable for 3D quantitative characterization of vascular networks, and that Fzd4 and Fzd6 genes have a deep patterning effect on arterial vessel morphogenesis that may determine its functional efficiency.
Ključne besede: cell polarity, vascular network, metrics, quantitative analyses
Objavljeno v DKUM: 19.06.2017; Ogledov: 1329; Prenosov: 405
Celotno besedilo (2,56 MB)
Gradivo ima več datotek! Več...

Ključne besede: biofizika, gladke mišice, krčenje mišic, matematični modeli, biophysics, smooth muscles, contractions, mathematical modelling
Objavljeno v DKUM: 10.07.2015; Ogledov: 1667; Prenosov: 43
Povezava na celotno besedilo

Opis: We investigated theoretically and experimentally the ▫$Ca^{2+}$▫-contraction couplingin rat tracheal smooth muscle. ▫$[Ca^{2+}]_i$▫, isometric contraction and myosin light chain (MLC) phosphorylation were measured in response to 1 mM carbachol. Theoretical modeling consisted in coupling a model of ▫$Ca^{2+}-dependent$▫ MLC kinase (MLCK) activation with a four-state model of smooth muscle contractile apparatus. Stimulation resulted in a short-time contraction obtained within 1 min, followed by a long-time contraction up to the maximal force obtained in 30 min. ML-7 and Wortmannin (MLCK inhibitors) abolished the contraction. Chelerythrine (PKC inhibitor) did not change the short-time, but reduced the long-time contraction. ▫$[Ca^{2+}]_i$▫ responses of isolated myocytes recorded during the first 90 s consisted in a fast peak, followed by a plateau phase and, in 28 % of the cells, superimposed ▫$Ca^{2+}$▫ oscillations. MLC phosphorylation was maximal at 5 s and then decreased, whereas isometric contraction followed a Hill-shaped curve. The model properlypredicts the time course of MLC phosphorylation and force of the short-time response. With oscillating ▫$Ca^{2+}$▫ signal, the predicted force does not oscillate. According to the model, the amplitude of the plateau and the frequency of oscillations encode for the amplitude of force, whereas the peak encodes for force velocity. The long-time phase of the contraction, associated with a second increase in MLC phosphorylation, may be explained, at least partially, by MLC phosphatase (MLCP) inhibition, possibly via PKC inhibition.
Ključne besede: biophysics, mathematical modelling, modelling, calcium oscillations, contractions, force development, muscle cells, smooth muscles, myosin kinase
Objavljeno v DKUM: 07.06.2012; Ogledov: 2091; Prenosov: 102
Povezava na celotno besedilo