Does Plasminogen Activator Inhibitor-1 Drive Lymphangiogenesis?

The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and by regulating endothelial cell survival and migration. Protease system's role in lymphangiogenesis is unknown yet. Thus, based on its important pro-angiogenic effect, we hypothesized that PAI-1 may regulate lymphangiogenesis associated at least with metastatic dissemination of cancer cells. To address this issue, we studied the impact of PAI-1 deficiency in various murine models of tumoral lymphangiogenesis. Wild-type PAI-1 proficient mice were used as controls. We provide for the first time evidence that PAI-1 is dispensable for tumoral lymphangiogenesis associated with breast cancers either induced by mammary carcinoma cell injection or spontaneously appearing in transgenic mice expressing the polyomavirus middle T antigen (PymT) under the control of a mouse mammary tumor virus long-terminal repeat promoter (MMTV-LTR). We also investigated inflammation-related lymphatic vessel recruitment by using two inflammatory models. PAI-1 deficiency did neither affect the development of lymphangioma nor burn-induced corneal lymphangiogenesis. These novel data suggest that vascular remodelling associated with lymphangiogenesis and angiogenesis involve different molecular determinants. PAI-1 does not appear as a potential therapeutic target to counteract pathological lymphangiogenesis

Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis.

ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases. These proteases have been largely implicated in tissue remodeling and angiogenesis associated with physiological and pathological processes. To elucidate the in vivo functions of ADAMTS-12, we have generated a knockout mouse strain (Adamts12−/−) in which Adamts12 gene was deleted. The mutant mice had normal gestations and no apparent defects in growth, life span and fertility. By applying three different in vivo models of angiogenesis (malignant keratinocyte transplantation, Matrigel plug and aortic ring assays) to Adamts12−/− mice, we provide evidence for a protective effect of this host enzyme toward angiogenesis and cancer progression. In the absence of Adamts-12, both the angiogenic response and tumor invasion into host tissue were increased. Complementing results were obtained by using medium conditioned by cells overexpressing human ADAMTS-12, which inhibited vessel outgrowth in the aortic ring assay. This angioinhibitory effect of ADAMTS-12 was independent of its enzymatic activity as a mutated inactive form of the enzyme was similarly efficient in inhibiting endothelial cell sprouting in the aortic ring assay than the wild-type form. Altogether, our results show that ADAMTS-12 displays antiangiogenic properties and protect the host toward tumor progression

Planet Formation Imager (PFI): science vision and key requirements

The Planet Formation Imager (PFI) project aims to provide a strong scientific vision for ground-based optical astronomy beyond the upcoming generation of Extremely Large Telescopes. We make the case that a breakthrough in angular resolution imaging capabilities is required in order to unravel the processes involved in planet formation. PFI will be optimised to provide a complete census of the protoplanet population at all stellocentric radii and over the age range from 0.1 to ~100 Myr. Within this age period, planetary systems undergo dramatic changes and the final architecture of planetary systems is determined. Our goal is to study the planetary birth on the natural spatial scale where the material is assembled, which is the "Hill Sphere" of the forming planet, and to characterise the protoplanetary cores by measuring their masses and physical properties. Our science working group has investigated the observational characteristics of these young protoplanets as well as the migration mechanisms that might alter the system architecture. We simulated the imprints that the planets leave in the disk and study how PFI could revolutionise areas ranging from exoplanet to extragalactic science. In this contribution we outline the key science drivers of PFI and discuss the requirements that will guide the technology choices, the site selection, and potential science/technology tradeoffs.S.K. acknowledges support from an STFC Rutherford Fellowship (ST/J004030/1) and Philip Leverhulme Prize (PLP-2013-110). Part of this work was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration

How to Build a Standardized Country-Specific Environmental Food Database for Nutritional Epidemiology Studies.

There is a lack of standardized country-specific environmental data to combine with nutritional and dietary data for assessing the environmental impact of individual diets in epidemiology surveys, which are consequently reliant on environmental food datasets based on values retrieved from a heterogeneous literature. The aim of this study was to compare and assess the relative strengths and limits of a database of food greenhouse gas emissions (GHGE) values estimated with a hybrid method combining input/output and LCA approaches, with a dataset of GHGE values retrieved from the literature. France is the geographical perimeter considered in this study, but the methodology could be applied to other countries. The GHGE of 402 foodstuffs, representative of French diet, were estimated using the hybrid method. In parallel, the GHGE of individual foods were collected from existing literature. Median per-food-category GHGE values from the hybrid method and the reviewed literature were found to correlate strongly (Spearman correlation was 0.83), showing similar rankings of food categories. Median values were significantly different for only 5 (out of 29) food categories, including the ruminant meats category for which the hybrid method gave lower estimates than those from existing literature. Analysis also revealed that literature values came from heterogeneous studies that were not always sourced and that were conducted under different LCA modeling hypotheses. In contrast, the hybrid method helps build reliably-sourced, representative national standards for product-based datasets. We anticipate this hybrid method to be a starting point for better environmental impact assessments of diets

Estimates calculated with the hybrid method (Red Boxes) and retrieved from the existing literature (icons), by food category.

<p>Shape of icon indicates the system boundary considered in the publication.</p

Food categories compared in terms of GHGE values from existing literature and GHGE values estimated using the hybrid method.

<p>The dotted line plots a fitted least squares regression without intercept. The solid line is the Y = X function. Dried fr, dried fruits and nuts; Proc fr, processed fruits and juices; Fresh fr, fresh fruits; Cooked veg, cooked vegetables; Raw veg, raw vegetables; Veg dishes, vegetarian mixed dishes.</p

Need for a better safety evaluation of food contact materials produced from resins

International audienceHistorically, due to the often overwhelming Complexity Of the Substances migrating from food contact materials (FCMs) into food, the specific legislation in Europe started from the Substances used to manufacture these materials and articles. There are, however, FCMs with migrates almost exclusively consisting of reaction products, such as those produced from resins used, e.g. for coatings (epoxy resins, polyesters, organosols, trimellitic acid resins). Since the reaction products do not necessarily have the same toxicological profile as the starting substances to produce the resins, the use of authorized starting substances does not rule out the migration of compounds endangering human health. The European framework Regulation 1935/2004 requires the safety of all substances migrating from FCMs into food. Resolution AP2004/1 on coatings of the Council of Europe Puts the emphasis on the safety evaluation of the migrants rather than that of the substances used for manufacturing the resins and then the coatings. Nonetheless, the Code of Practice for Coatings recently issued by industry focuses oil the evaluation of the starting substances to produce resins. The authors of this paper consider the present situation unsatisfactory. it is the duty of industry to respect the legal requirements and of the regulatory authorities to ensure that these requirements are met. The authors recommend setting a time limit to have this achieved

Monitoring 25-OH and 1,25-OH vitamin D levels in hemodialysis patients after starting therapy: Does it make sense?

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