Vascular smooth muscle cells remodel collagen matrices by long-distance action and anisotropic interaction

While matrix remodeling plays a key role in vascular physiology and pathology, the underlying mechanisms have remained incompletely understood. We studied the remodeling of collagen matrices by individual vascular smooth muscle cells (SMCs), clusters and monolayers. In addition, we focused on the contribution of transglutaminase 2 (TG2), which plays an important role in the remodeling of small arteries. Single SMCs displaced fibers in collagen matrices at distances up to at least 300 μm in the course of 8–12 h. This process involved both ‘hauling up’ of matrix by the cells and local matrix compaction at a distance from the cells, up to 200 μm. This exceeded the distance over which cellular protrusions were active, implicating the involvement of secreted enzymes such as TG2. SMC isolated from TG2 KO mice still showed compaction, with changed dynamics and relaxation. The TG active site inhibitor L682777 blocked local compaction by wild type cells, strongly reducing the displacement of matrix towards the cells. At increasing cell density, cells cooperated to establish compaction. In a ring-shaped collagen matrix, this resulted in preferential displacement in the radial direction, perpendicular to the cellular long axis. This process was unaffected by inhibition of TG2 cross-linking. These results show that SMCs are capable of matrix remodeling by prolonged, gradual compaction along their short axis. This process could add to the 3D organization and remodeling of blood vessels based on the orientation and contraction of SMCs

Performance and profit sensitivity to risk: a practical evaluation of the agro-industrial projects developed by Israeli companies for the CIS and Eastern European countries

International companies take part in many tenders for agro-industrial projects in the Commonwealth of Independent States and Eastern European countries. The market for these projects is analyzed and found to be favorable for companies and developers. Major projects developed in recent years are presented and evaluated in terms of financial performance. Additionally, a method of project evaluation by profit sensitivity to risk criterion is proposed. In this method, the approximate formula for profit sensitivity to risk (when basic production and market assumptions change simultaneously) is derived using a cost-volume-profit model. This method allows minimal calculations to explain profit sensitivity and elasticity within the usual indicators of business planning: operational profitability and degree of operating leverage. The consistency of project ranking is examined using Cronbach's alpha and correlation coefficients. The ranks obtained by various performance criteria are found to be consistent with each other, but not with those obtained by profit sensitivity to risk. In terms of elasticity, project profitability is a much stronger influence than the degree of operating leverage on profit sensitivity to risk