Getting in and out of shape : relevance for organ formation and cancer

A central question during development is how single cells form functional multi-cellularorgan structures. The high reproducibility indicates intricate synchronization of cellular behaviors such as migration, proliferation and cell shape changes. How mechanical signals or forces regulate cell shape changes is less studied, however several reports indicate a role of mechanical forces in malignancy Increased force or stiffness in the matrix cause loss of tissue architecture associated with tumor progression. Important hallmarks of advanced cancerous tumors are the loss of epithelial character from the original tissue and the appearance of more mesenchymal-like cells, especially at the periphery, where the tumor cells are in contact with surrounding stromal cells. Typical of this epithelial–mesenchymal transition (EMT) is the loss of cell–cell adhesion and apical–basal cell polarity as well as the increased motility of tumor cells. Although the importance of EMT for tumor progression is widely accepted muchless is known about the relationship between cell polarity and early events in carcinogenesis. The aim of this thesis was to study the role of AmotL2 during blood vessel formation and tumor progression. In this thesis it is demonstrated that angiomotin-like 2 is expressed as two isoforms with distinct functions. The longer isoform p100 AmotL2 is localized to cell-cell junctions, and associates to the VE-cadherin complex where it couples adherent junctions to contractile actin fibers. Using gene inactivation strategies in zebrafish, mouse and endothelial cell culture systems, we show that inactivation of p100 AmotL2 dissociates VE-cadherin from cytoskeletal tensile forces that affect endothelial cell shape. We report that AmotL2 is essential for vascular lumen expansion, by transmission of junctional force between cells. We propose a novel mechanism for which transmission of mechanical force is essential for the coordination of cellular morphogenesis. This thesis also provides data regarding p60 AmotL2, the shorter isoform. We show that hypoxic stress activates c-Fos dependent transcription of p60 AmotL2 resulting in disruption of apical basal polarity. Activation of p60 AmotL2 results in formation or of largeintracellular vesicles that sequester Crb3 and Par3 polarity complexes inside the cell. In human tumors from breast and colon cancer patient’s p60 AmotL2 expression correlates with loss of tissue architecture and cell polarity. Furthermore we provide data showing that p60 AmotL2 acts as a p100 AmotL2 antagonist sequestering p100 into intracellular vesicles. This results in alterations in actin reorganization and weakened cell-cell adhesions. These data point to a novel pathway, which controls metastatic sprea

Riordan graphs II : spectral properties

The authors of this paper have used the theory of Riordan matrices to introduce the notion of a Riordan graph in [3]. Riordan graphs are proved to have a number of interesting (fractal) properties, and they are a far-reaching generalization of the well known and well studied Pascal graphs and Toeplitz graphs, and also some other families of graphs. The main focus in [3] is the study of structural properties of families of Riordan graphs obtained from certain infinite Riordan graphs. In this paper, we use a number of results in [3] to study spectral properties of Riordan graphs. Our studies include, but are not limited to the spectral graph invariants for Riordan graphs such as the adjacency eigenvalues, (signless) Laplacian eigenvalues, nullity, positive and negative inertia indices, and rank. We also study determinants of Riordan graphs, in particular, giving results about determinants of Catalan graphs

Riordan graphs I : structural properties

In this paper, we use the theory of Riordan matrices to introduce the notion of a Riordan graph. The Riordan graphs are a far-reaching generalization of the well known and well studied Pascal graphs and Toeplitz graphs, and also some other fami- lies of graphs. The Riordan graphs are proved to have a number of interesting (fractal) properties, which can be useful in creating computer networks with certain desirable features, or in obtaining useful information when designing algorithms to compute values of graph invariants. The main focus in this paper is the study of structural properties of families of Riordan graphs obtained from infinite Riordan graphs, which includes a fundamental decomposition theorem and certain conditions on Riordan graphs to have an Eulerian trail/cycle or a Hamiltonian cycle. We will study spectral properties of the Riordan graphs in a follow up paper

Reticulated livedoid skin patterns after soft-tissue filler–related vascular adverse events

Background: For the treatment of vascular adverse events caused by filler injections, duplex ultrasound imaging may be used. The findings of duplex ultrasound examination and the clinical features of reticulated livedoid skin patterns were compared with the hemifaces anatomy. Objective: The objective of this study was to link the reticulated livedoid skin patterns to the corresponding duplex ultrasound findings and the facial perforasomes. Methods: Duplex ultrasound imaging was used for the diagnosis and treatment of vascular adverse events. The clinical features and duplex ultrasound findings of 125 patients were investigated. Six cadaver hemifaces were examined to compare the typical livedo skin patterns with the vasculature of the face. Results: Clinically, the affected skin showed a similar reticulated pattern in each facial area corresponding with arterial anatomy and their perforators in the cadaver hemifaces. With duplex ultrasound, a disturbed microvascularization in the superficial fatty layer was visualized. After hyaluronidase injection, clinical improvement of the skin pattern was seen. Normalization of blood flow was noted accompanied by restoration of flow in the corresponding perforator artery. The skin patterns could be linked to the perforators of the superficial fat compartments. Conclusion: The livedo skin patterns seen in vascular adverse events may reflect the involvement of the perforators.</p

Finite element analysis of biomechanical interactions of a subcutaneous suspension suture and human face soft-tissue: a cadaver study

In order to study the local interactions between facial soft-tissues and a Silhouette Soft suspension suture, a CE marked medical device designed for the repositioning of soft tissues in the face and the neck, Finite element simulations were run, in which a model of the suture was embedded in a three-layer Finite Element structure that accounts for the local mechanical organization of human facial soft tissues. A 2D axisymmetric model of the local interactions was designed in ANSYS, in which the geometry of the tissue, the boundary conditions and the applied loadings were considered to locally mimic those of human face soft tissue constrained by the suture in facial tissue repositioning. The Silhouette Soft suture is composed of a knotted thread and sliding cones that are anchored in the tissue. Hence, simulating these interactions requires special attention for an accurate modelling of contact mechanics. As tissue is modelled as a hyper-elastic material, the displacement of the facial soft tissue changes in a nonlinear way with the intensity of stress induced by the suture and the number of the cones. Our simulations show that for a 4-cone suture a displacement of 4.35mm for a 2.0N external loading and of 7.6mm for 4.0N. Increasing the number of cones led to the decrease in the equivalent local strain (around 20%) and stress (around 60%) applied to the tissue. The simulated displacements are in general agreement with experimental observations

The qq-Analogue of Zero Forcing for Certain Families of Graphs

Zero forcing is a combinatorial game played on a graph with the ultimate goal of changing the colour of all the vertices at minimal cost. Originally this game was conceived as a one player game, but later a two-player version was devised in-conjunction with studies on the inertia of a graph, and has become known as the $q$-analogue of zero forcing. In this paper, we study and compute the $q$-analogue zero forcing number for various families of graphs. We begin with by considering a concept of contraction associated with trees. We then significantly generalize an equation between this $q$-analogue of zero forcing and a corresponding nullity parameter for all threshold graphs. We close by studying the $q$-analogue of zero forcing for certain Kneser graphs, and a variety of cartesian products of structured graphs.Comment: 29 page