Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo

Endothelial tip cells guide angiogenic sprouts by exploring the local environment for guidance cues such as vascular endothelial growth factor (VegfA). Here we present Flt1 (Vegf receptor 1) loss- and gain-of-function data in zebrafish showing that Flt1 regulates tip cell formation and arterial branching morphogenesis. Zebrafish embryos expressed soluble Flt1 (sFlt1) and membrane-bound Flt1 (mFlt1). In Tg(flt1(BAC):yfp) × Tg(kdrl:ras-cherry)(s916) embryos, flt1:yfp was expressed in tip, stalk and base cells of segmental artery sprouts and overlapped with kdrl:cherry expression in these domains. flt1 morphants showed increased tip cell numbers, enhanced angiogenic behavior and hyperbranching of segmental artery sprouts. The additional arterial branches developed into functional vessels carrying blood flow. In support of a functional role for the extracellular VEGF-binding domain of Flt1, overexpression of sflt1 or mflt1 rescued aberrant branching in flt1 morphants, and overexpression of sflt1 or mflt1 in controls resulted in short arterial sprouts with reduced numbers of filopodia. flt1 morphants showed reduced expression of Notch receptors and of the Notch downstream target efnb2a, and ectopic expression of flt4 in arteries, consistent with loss of Notch signaling. Conditional overexpression of the notch1a intracellular cleaved domain in flt1 morphants restored segmental artery patterning. The developing nervous system of the trunk contributed to the distribution of Flt1, and the loss of flt1 affected neurons. Thus, Flt1 acts in a Notch-dependent manner as a negative regulator of tip cell differentiation and branching. Flt1 distribution may be fine-tuned, involving interactions with the developing nervous system.

Association behavior of the synthetic protein-lipid complex analogues

Hypercoiling poly(styrene-ALT-maleic anhydride) (PSMA) is known to undergo conformational transition in response to environmental stimuli. This behavior allows it to associate with the phospholipid, 2-dilauryl-SN-glycero-3- phosphocholine (DLPC) to produce nanostructures analogous to lipoproteins. The complex represents a new bio-mimetic delivery vehicle with applications in the cosmetic and pharmaceutical industries. This study investigates, for the first time, the association behavior of PSMA and DLPC through the combination of different analytical techniques. The results indicate that the association is primarily driven by hydrophobic interactions and depends on various factors including the polymer/lipid ratio, the polymer molecular weight and the pH of the aqueous environment. The conformational transition of PSMA leads to the formation of discrete micellar complexes involving anisotropic-to-isotropic lipid phase transformation. As the number of hydrophobic moieties in the polymer is increased, the pH-dependent conformational transition of the polymer plays less important part in achieving this phase transition of the lipid. © (2012) Trans Tech Publications.

Formation and precise geometry control of SNAP microresonators by external electrostatic fields

In SNAP (Surface nanoscale axial photonics) resonators propagation of a slow whispering gallery mode along an optical fiber is controlled by nanoscale variation of the effective radius of the fiber [1]. Similar behavior can be realized in so - called nanobump microresonators in which the introduced variation of the effective radius is asymmetric, i.e. depends on the axial coordinate [2]. The possibilities of realization of such structures “on the fly” in an optical fiber by applying external electrostatic fields to it is discussed in this work. It is shown that local variations in effective radius of the fiber and in its refractive index caused by external electric fields can be large enough to observe SNAP structure - like behavior in an originally flat optical fiber. Theoretical estimations of the introduced refractive index and effective radius changes and results of finite element calculations are presented. Various effects are taken into account: electromechanical (piezoelectricity and electrostriction), electro-optical (Pockels and Kerr effects) and elasto-optical effect. Different initial fibre cross-sections are studied. The aspects of use of linear isotropic (such as silica) and non-linear anisotropic (such as lithium niobate) materials of the fiber are discussed. REFERENCES [1] M. Sumetsky, J. M. Fini, Opt. Exp. 19, 26470 (2011). [2] L. A. Kochkurov, M. Sumetsky, Opt. Lett. 40, 1430 (2015).