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Anti-angiogenic therapies have generated significant interest for their potential to combat tumor growth. However, tumor overproduction of pro-angiogenic ligands can overcome these therapies, hampering success of this approach. To circumvent this problem, we target the resynthesis of phosphoinositides consumed during intracellular transduction of pro-angiogenic signals in endothelial cells (EC), thus harnessing the tumors own production of excess stimulatory ligands to deplete adjacent ECs of the capacity to respond to these signals. Using zebrafish and human endothelial cells in vitro, we show ECs deficient in CDP-diacylglycerol synthase 2 are uniquely sensitive to increased vascular endothelial growth factor (VEGF) stimulation due to a reduced capacity to re-synthesize phosphoinositides, including phosphatidylinositol-(4,5)-bisphosphate (PIP2), resulting in VEGF-exacerbated defects in angiogenesis and angiogenic signaling. Using murine tumor allograft models, we show that systemic or EC specific suppression of phosphoinositide recycling results in reduced tumor growth and tumor angiogenesis. Our results suggest inhibition of phosphoinositide recycling provides a useful anti-angiogenic approach.

Purpose/Objectives: Although meals offered through the National School Lunch Program (NSLP) have been found to be of higher dietary quality than packed lunches, roughly 40% of students bring packed lunches for a variety of reasons, including cost. The purpose of this study was to explore costs, including time, of NSLP and packed lunches. Methods: Data from the lunches of 1,289 pre-kindergarten and kindergarten students enrolled in three schools in southwest Virginia were used for this study, and categorized as homemade packed lunches, convenience packed lunches, replicated school lunches, and NSLP lunches. Each lunch was assigned a food cost based on retail purchase of lunch contents. Each lunch was also assigned a time cost by evaluating the amount of time to prepare each lunch, with a monetary value for labor computed. A full-cost for each lunch was determined by combining food cost and time cost. Nonparametric tests were used to compare the food cost, time cost, and the full cost of the meals. Medians were computed and compared due to outliers in the data. Descriptive statistics were used to calculate the median food cost of sugar-sweetened beverages and desserts in packed lunches. Results: Statistically significant differences in median food costs were found between homemade packed lunches ($1.55) and replicated school lunches ($2.11), convenience packed lunches ($2.12), and NSLP lunches ($2.15). The homemade packed lunch provided a statistically significant reduction in food cost compared to NSLP. When incorporating preparation time (full cost), all one-sided pairwise comparisons of lunch cost were found to be statistically significant (p-values less than 0.0001) in terms of their median values: NSLP ($2.15), convenience packed lunches ($2.56), homemade packed lunches ($2.92), and replicated school lunches ($11.32). Seventy-six percent (414 of 545) of packed lunches contained sugar-sweetened beverages and/or dessert food items, accounting for one-fifth (median of 20.07%) of the food cost of all observed packed lunches. Applications to Child Nutrition Professionals: When time is computed as part of the total cost of NSLP versus packed lunch options, including homemade packed lunches, replicated school meals, and convenience lunch options, the NSLP is the least expensive choice. In conjunction with the nutritional benefits of the NSLP, time-cost data may be used to develop interventions or campaigns on the benefits of participating in the NLSP.

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

Mural cells are critically important for the development, maturation, and maintenance of the blood vasculature. Pericytes are predominantly observed in capillaries and venules, while vascular smooth muscle cells (VSMCs) are found in arterioles, arteries, and veins. In this study, we have investigated functional differences between human pericytes and human coronary artery smooth muscle cells (CASMCs) as a model VSMC type. We compared the ability of these two mural cells to invade three-dimensional (3D) collagen matrices, recruit to developing human endothelial cell (EC)-lined tubes in 3D matrices and induce vascular basement membrane matrix assembly around these tubes. Here, we show that pericytes selectively invade, recruit, and induce basement membrane deposition on EC tubes under defined conditions, while CASMCs fail to respond equivalently. Pericytes dramatically invade 3D collagen matrices in response to the EC-derived factors, platelet-derived growth factor (PDGF)-BB, PDGF-DD, and endothelin-1, while minimal invasion occurs with CASMCs. Furthermore, pericytes recruit to EC tube networks, and induce basement membrane deposition around assembling EC tubes (narrow and elongated tubes) when these cells are co-cultured. In contrast, CASMCs are markedly less able to perform these functions showing minimal recruitment, little to no basement membrane deposition, with wider and shorter tubes. Our new findings suggest that pericytes demonstrate much greater functional ability to invade 3D matrix environments, recruit to EC-lined tubes and induce vascular basement membrane matrix deposition in response to and in conjunction with ECs. [ABSTRACT FROM AUTHOR]

Shortening estimates for fold-thrust belts seldom take into consideration outcrop-scale folding, especially folding related to prethrusting layer-parallel shortening (LPS) and flattening. The Pindos belt of the Peloponnese contains products of Maastrichtian to Paleocene tectonic shortening amenable to assessing strain partitioning. Shortening there initiated with LPS, including outcrop-scale folding, which was superseded by thrusting and macrofolding, with both macromechanisms producing additional outcrop-scale folding and (or) form-modification of initial LPS outcrop-scale folds. Skourlis and Doutsos (2003. International Journal of Earth Sciences, 92: 891-903) concluded that total shortening in this region was 68%, the summation of ~15% LPS, ~6% fault-related macrofolding, and ~47% thrust-slip translation. But even this degree of shortening may be underestimated when outcrop-scale folding is considered. Two limestone-dominated Cretaceous formations and one Cretaceous--Eocene formation of limestone and mudstone display spectacular outcrop-scale folding produced by true multilayer behavior, internal buckling, and disharmonic quasi-flexural folding. Fold forms vary from chevron buckling of multilayers to more rounded folding of true multilayers to disharmonic flattened folds in pseudo-bedded limestone. Ramsay analysis of layer thickness variations across individual disharmonic folds underscores the disharmonic fold forms and intense degree of pressure dissolution generated fold flattening. Line-length shortening for well exposed 'packages' of LPS outcrop-scale folding is as high as 30%, but overlying and underlying panels may be more modestly folded and (or) flattened, suggesting that shortening transfer mechanisms may have caused some sections to be bypassed. Achieving more meaningful shortening estimates of the outcrop-scale folding within an entire progressive deformation will require understanding of the partitioning of distribution of this folding regionally. Key words: folding, layer-parallel shortening, fold flattening, disharmonic folding, thrust belts. Les estimations du raccourcissement de ceintures de plissement et de chevauchement tiennent rarement compte du plissement a l'echelle de l'affleurement, tout particulierement le plissement associe au raccourcissement parallele aux couches (RPC) et a l'aplatissement pre-chevauchement. La ceinture de Pindos du Peloponnese contient des produits d'un raccourcissement tectonique maastrichtien a paleocene qui se pretent a l'evaluation du partitionnement de la deformation. Le raccourcissement y a debute avec un RPC, dont un plissement a l'echelle de l'affleurement, sur lequel se sont superposes un chevauchement et un plissement macroscopique, ces deux derniers mecanismes produisant, a l'echelle de l'affleurement, un autre plissement ou modification des formes des plis initiaux a l'echelle de l'affleurement resultant du RPC. Skourlis et Doutsos (2003. International Journal of Earth Sciences, 92: 891-903) concluaient a un raccourcissement total dans cette region de 68 %, soit la somme de ~15 % de RPC, ~6 % de plissement macroscopique associe a des failles et ~47 % de translation associee au rejet de failles de chevauchement. Mais meme ce degre de raccourcissement pourrait etre sous-estime si le plissement a l'echelle de l'affleurement est pris en consideration. Deux formations cretacees dans lesquels le calcaire domine et une formation cretacee--eocene de calcaire et mudstone presentent un plissement spectaculaire a l'echelle de l'affleurement produit par un vrai comportement multicouche, un flambage interne et un plissement dysharmonique par quasi-flexion. Les formes des plis vont du flambage en chevrons de multicouches au plissement plus arrondi de vraies multicouches a des plis aplatis dysharmoniques dans du calcaire pseudo-lite. L'analyse de Ramsay des variations de l'epaisseur des couches au sein de plis dysharmoniques souligne les formes dysharmoniques des plis et l'intensite de l'aplatissement par dissolution par pression des plis. Si le raccourcissement des longueurs de lignes pour des <> bien exposes de plis de type RPC a l'echelle de l'affleurement peut atteindre 30 %, des panneaux sus-jacents et sous-jacents peuvent etre moins intensement plisses et aplatis, donnant a penser que des mecanismes de transfert du raccourcissement pourraient avoir fait en sorte que certaines sequences soient epargnees. Des estimations plus significatives du raccourcissement associe au plissement a l'echelle de l'affleurement pour l'ensemble d'une deformation progressive necessiteront une comprehension du partitionnement de la repartition de ce plissement a l'echelle regionale. [Traduit par la Redaction] Mots-cles: plissement, raccourcissement parallele aux couches, aplatissement des plis, plissement dysharmonique, ceintures de chevauchement., Introduction Forward To Celal Sengor: It is an honor to prepare a manuscript for a special volume in your name, for I value you as a colleague and friend. Your [...]

Schistosomiasis japonica is a major parasitic disease threatening millions of people in China. Though overall prevalence was greatly reduced during the second half of the past century, continued persistence in some areas and cases of re-emergence in others remain major concerns. As many regions in China are approaching disease elimination, obtaining quantitative data on Schistosoma japonicum parasites is increasingly difficult. This study examines the distribution of schistosomiasis in eastern China, taking advantage of the fact that the single intermediate host serves as a major transmission bottleneck. Epidemiological, population-genetic and high-resolution ecological data are combined to construct a predictive model capable of estimating the probability that schistosomiasis occurs in a target area ("spatially explicit schistosomiasis risk"). Results show that intermediate host genetic parameters are correlated with the distribution of endemic disease areas, and that five explanatory variables--altitude, minimum temperature, annual precipitation, genetic distance, and haplotype diversity-discriminate between endemic and non-endemic zones. Model predictions are correlated with human infection rates observed at the county level. Visualization of the model indicates that the highest risks of disease occur in the Dongting and Poyang lake regions, as expected, as well as in some floodplain areas of the Yangtze River. High risk areas are interconnected, suggesting the complex hydrological interplay of Dongting and Poyang lakes with the Yangtze River may be important for maintaining schistosomiasis in eastern China. Results demonstrate the value of genetic parameters for risk modeling, and particularly for reducing model prediction error. The findings have important consequences both for understanding the determinants of the current distribution of S. japonicum infections, and for designing future schistosomiasis surveillance and control strategies. The results also highlight how genetic information on taxa that constitute bottlenecks to disease transmission can be of value for risk modeling.