Mechanisms of lumen formation during sprouting angiogenesis in vivo

During development, vascular networks expand following a process known as sprouting angiogenesis. New vascular branches arise from pre-existing vessels through the coordinated migration and proliferation of endothelial cells, and eventually connect to form new vascular loops. The functionality of these new vessel segments is dependent on the opening of a central lumen to allow perfusion. While mechanisms of lumen formation during the establishment of the primary vasculature by vasculogenesis have been well characterised, the mechanisms underlying lumen formation during sprouting angiogenesis in vivo are still poorly understood and subject to debate. In this work, I established high spatial and temporal imaging of apical membrane dynamics during sprouting angiogenesis in vivo, both in the zebrafish trunk vasculature and the mouse retina primary inner plexus. By doing so, I identified a novel mechanism of lumen formation, where blood flow expands luminal compartments by driving spherical deformations reminiscent of membrane blebs at the apical membrane of sprouting endothelial cells. Additionally, I show that this process, that I chose to term inverse membrane blebbing, is tightly controlled through local and transient recruitment and contraction of actomyosin at the surface of growing blebs. This mechanism eventually leads to the selective retraction of inverse blebs along the apical membrane, allowing unidirectional lumen expansion. When endothelial cells ability to retract is inhibited through expression of a dominant-negative form of myosin II, cells fail to lumenise or show dilated lumens with multiple unresolved side blebs and branches. Together, this work provides a mechanism for lumen expansion within sprouting endothelial cells in vivo, and identifies for the first time inverse blebbing as a reaction of membranes to high external pressure. In the context of sprouting endothelial cells, I show that a tight equilibrium between the forces exerted by the blood and the contractile responses from the cells is required for lumen expansion within angiogenic sprouts

Optimizing Segment Based Document Protection (Corrected Version)

In this paper we provide a corrected and generalized version of the scheme presented at SOFSEM\u272012 in our paper ``Optimizing Segment Based Document Protection\u27\u27 (SOFSEM 2012: Theory and Practice of Computer Science, LNCS 7147, pp. 566-575). We develop techniques for protecting documents with restricted access rights. In these documents so called \emph{segments} are encrypted. Different segments may be encrypted with different keys so that different user may be given different \emph{access rights}. Hierarchy of access rights is represented by means of a directed acyclic \emph{access graph}. The segments are encrypted with keys - where each key corresponds to one node in the access graph. The main feature of the access graph is that if there is an arch $\overrightarrow{AB}$ in the graph, then all segments labelled with $B$ can be decrypted with the key corresponding to node $A$. We show how to minimize the space overhead necessary for auxiliary keying information stored in the document. We provide an algorithm based on node disjoint paths in the access graph and key derivation based on one-way functions. Our current solution, based on maximal weighted matchings, provides an optimal solution for creating subdocuments, in case when frequency of creating each subdocument is known

Blood flow drives lumen formation by inverse membrane blebbing during angiogenesis in vivo

How vascular tubes build, maintain and adapt continuously perfused lumens to meet local metabolic needs remains poorly understood. Recent studies showed that blood flow itself plays a critical role in the remodelling of vascular networks, and suggested it is also required for the lumenization of new vascular connections. However, it is still unknown how haemodynamic forces contribute to the formation of new vascular lumens during blood vessel morphogenesis. Here we report that blood flow drives lumen expansion during sprouting angiogenesis in vivo by inducing spherical deformations of the apical membrane of endothelial cells, in a process that we have termed inverse blebbing. We show that endothelial cells react to these membrane intrusions by local and transient recruitment and contraction of actomyosin, and that this mechanism is required for single, unidirectional lumen expansion in angiogenic sprouts. Our work identifies inverse membrane blebbing as a cellular response to high external pressure. We show that in the case of blood vessels such membrane dynamics can drive local cell shape changes required for global tissue morphogenesis, shedding light on a pressure-driven mechanism of lumen formation in vertebrates

Axiomatic Design: Making the Abstract Concrete

Design broadly defined deals with mapping from societal wants or needs to means for satisfying these needs. Axiomatic design is a well-known approach to design that was initially proposed by Nam P. Suh in the late 1970s. Since that time, it has underpinned much academic research in engineering design; it has been taught internationally as part of engineering curricula; and it has been used across many industries. This paper presents a summary of axiomatic design and provides practical suggestions for best practices in implementation and education

Pericytes or mesenchymal stem cells: is that the question?

For almost a decade, mesenchymal stem cells (MSCs) were believed to reside as perivascular cells in vivo. In this issue of Cell Stem Cell, Guimaraes-Camboa et al. (2017) challenge this idea and use lineage tracing to demonstrate that perivascular cells do not behave as tissue-specific progenitors in various organs, despite showing MSC potential in vitro

Selected physical medicine interventions in the treatment of diabetic foot syndrome

The diabetic foot syndrome (DFS) is among chronic complications of diabetes mellitus; it can affect individuals with both type 1 and type 2 diabetes. Diabetic patients have up to a 25% lifetime risk of developing DFS, which is both a medical and social problem. Several studies have indicated that, apart from pharmacotherapy and modern active wound dressings, physical medicine also has a role in prevention and management of diabetic foot ulcers. The paper presents physical medicine interventions most recognized in the conservative management of DFS.The diabetic foot syndrome (DFS) is among chronic complications of diabetes mellitus; it can affect individuals with both type 1 and type 2 diabetes. Diabetic patients have up to a 25% lifetime risk of developing DFS, which is both a medical and social problem. Several studies have indicated that, apart from pharmacotherapy and modern active wound dressings, physical medicine also has a role in prevention and management of diabetic foot ulcers. The paper presents physical medicine interventions most recognized in the conservative management of DFS

Selected physical medicine interventions in the treatment of diabetic foot syndrome

The diabetic foot syndrome (DFS) is among chronic complications of diabetes mellitus; it can affect individuals with both type 1 and type 2 diabetes. Diabetic patients have up to a 25% lifetime risk of developing DFS, which is both a medical and social problem. Several studies have indicated that, apart from pharmacotherapy and modern active wound dressings, physical medicine also has a role in prevention and management of diabetic foot ulcers. The paper presents physical medicine interventions most recognized in the conservative management of DFS

Artery-vein specification in the zebrafish trunk is pre-patterned by heterogeneous Notch activity and balanced by flow-mediated fine tuning

How developing vascular networks acquire the right balance of arteries, veins and lymphatic vessels to efficiently supply and drain tissues is poorly understood. In zebrafish embryos, the robust and regular 50:50 global balance of intersegmental veins and arteries that form along the trunk, prompts the intriguing question how the organism keeps "count". Previous studies suggest that the ultimate fate of an intersegmental vessel (ISV) is determined by the identity of the approaching secondary sprout emerging from the posterior cardinal vein (PCV). Here, we show that the formation of a balanced trunk vasculature involves an early heterogeneity in endothelial cell (EC) behavior and Notch signaling activity in the seemingly identical primary ISVs that is independent of secondary sprouting and flow. We show that Notch signaling mediates the local patterning of ISVs, and an adaptive flow-mediated mechanism subsequently fine-tunes the global balance of arteries and veins along the trunk. We propose that this dual mechanism provides the adaptability required to establish a balanced network of arteries, veins and lymphatic vessels

A new crystal modification of diammonium hydrogen phosphate, (NH4)2(HPO4)

The addition of hexa­fluorido­phosphate salts (ammonium, silver, thallium or potassium) is usually used to precipitate complex cations from aqueous solutions. It has long been known that PF6 − is sensitive towards hydrolysis under acidic conditions [Gebala & Jones (1969 ▶). J. Inorg. Nucl. Chem. 31, 771–776; Plakhotnyk et al. (2005 ▶). J. Fluorine Chem. 126, 27–31]. During the course of our investigation into coinage metal complexes of diphosphine ligands, we used ammonium hexa­fluorido­phosphate in order to crystallize [Ag(diphos­phine)2]PF6 complexes. From these solutions we always obtained needle-like crystals which turned out to be the title compound, 2NH4 +·HPO4 2−. It was received as the hydrolysis product of NH4PF6. The crystals are a new modification of diammonium hydrogen phosphate. In contrast to the previously published polymorph [Khan et al. (1972 ▶). Acta Cryst. B28, 2065–2069], Z′ of the title compound is 2. In the new modification of the title compound, there are eight mol­ecules of (NH4)2(HPO4) in the unit cell. The structure consists of PO3OH and NH4 tetra­hedra, held together by O—H⋯O and N—H⋯O hydrogen bonds