Systemic Sclerosis Sera Impair Angiogenic Performance of Dermal Microvascular Endothelial Cells: Therapeutic Implications of Cyclophosphamide

In systemic sclerosis (SSc), dermal capillaries are progressively lost with consequent chronic tissue hypoxia insufficiently compensated by angiogenesis. Clinical studies reported that intravenous cyclophosphamide (CYC) may improve SSc-related peripheral microvascular damage. Recently, we showed that CYC treatment may normalize SSc sera-induced abnormalities in endothelial cell-matrix interactions. Our objective was to evaluate in vitro the effects of sera from treatment-naïve or CYC-treated SSc patients on dermal blood microvascular endothelial cell (dMVEC) angiogenesis, migration, proliferation and apoptosis. dMVECs were challenged with sera from 21 SSc patients, treatment-naïve (n = 8) or under CYC treatment (n = 13), and 8 healthy controls. Capillary morphogenesis on Geltrex matrix was significantly reduced upon challenge with sera from naïve SSc patients compared with healthy controls. When dMVECs were challenged with sera from CYC-treated SSc patients, their angiogenic capacity was comparable to that of cells treated with healthy sera. Wound healing capacity and chemotaxis in Boyden chamber were both significantly decreased in the presence either of naïve or CYC-treated SSc sera compared with healthy sera. WST-1 assay revealed that cell proliferation was significantly decreased in dMVECs challenged with sera from naïve SSc patients compared with healthy sera. Conversely, dMVEC proliferation was not impaired in the presence of sera from CYC-treated SSc patients. Accordingly, the percentage of TUNEL-positive apoptotic dMVECs was significantly higher in the presence of sera from naïve SSc patients than healthy controls, while CYC-treated SSc sera did not induce dMVEC apoptosis. Levels of the angiostatic mediators endostatin, pentraxin 3, angiostatin and matrix metalloproteinase-12 were all significantly elevated in sera from naïve SSc patients compared with sera from both healthy controls and CYC-treated SSc patients. In SSc, CYC treatment might boost angiogenesis and consequently improve peripheral microangiopathy through the normalization of the endothelial cell-matrix interactions, reduction of endothelial cell apoptosis and rebalance of dysregulated angiostatic factors

Territorial Resilience: Toward a Proactive Meaning for Spatial Planning

The international debate on resilience has grown around the ability of a community to prepare for and adapt to natural disasters, with a growing interest in holistically understanding complex systems. Although the concept of resilience has been investigated fromdifferent perspectives, the lack of understanding of its conceptual comprehensive aspects presents strong limitations for spatial planning and for the adoption of policies and programs for its measurement and achievement. In this paper, we refer to “territorial resilience” as an emerging concept capable of aiding the decision-making process of identifying vulnerabilities and improving the transformation of socio-ecological and technological systems (SETSs). Here,we explore the epistemology of resilience, reviewing the origins and the evolution of this term, providing evidence on how this conceptual umbrella is used by different disciplines to tackle problem-solving that arises from disaster management and command-control practices to augment the robustness. Assuming the SETSs paradigm, the seismic and structural engineering, social sciences and history, urban planning and climatology perspectives intersects providing different analytical levels of resilience, including vulnerability and patrimony from a community and cultural perspective. We conclude that territorial resilience surpasses the analytical barriers between different disciplines, providing a useful concept related to complex problem-solving phenomena for land use planning, opening a new research question: how can territorial resilience be measured, acknowledging different units and levels of analysis aiding decision-making in spatial plans and projects? In attempting to understand a resilient system, quantitative and qualitative measurements are crucial to supporting planning decisions

PHOX2B-Mediated Regulation of ALK Expression: In Vitro Identification of a Functional Relationship between Two Genes Involved in Neuroblastoma

BACKGROUND: Neuroblastoma (NB) is a severe pediatric tumor originating from neural crest derivatives and accounting for 15% of childhood cancer mortality. The heterogeneous and complex genetic etiology has been confirmed with the identification of mutations in two genes, encoding for the receptor tyrosine kinase Anaplastic Lymphoma Kinase (ALK) and the transcription factor Paired-like Homeobox 2B (PHOX2B), in a limited proportion of NB patients. Interestingly, these two genes are overexpressed in the great majority of primary NB samples and cell lines. These observations led us to test the hypothesis of a regulatory or functional relationship between ALK and PHOX2B underlying NB pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Following this possibility, we first confirmed a striking correlation between the transcription levels of ALK, PHOX2B and its direct target PHOX2A in a panel of NB cell lines. Then, we manipulated their expression in NB cell lines by siRNA-mediated knock-down and forced over-expression of each gene under analysis. Surprisingly, PHOX2B- and PHOX2A-directed siRNAs efficiently downregulated each other as well as ALK gene and, consistently, the enhanced expression of PHOX2B in NB cells yielded an increment of ALK protein. We finally demonstrated that PHOX2B drives ALK gene transcription by directly binding its promoter, which therefore represents a novel PHOX2B target. CONCLUSIONS/SIGNIFICANCE: These findings provide a compelling explanation of the concurrent involvement of these two genes in NB pathogenesis and are going to foster a better understanding of molecular interactions at the base of the disease. Moreover, this work opens new perspectives for NBs refractory to conventional therapies that may benefit from the design of novel therapeutic RNAi-based approaches for multiple gene targets

Traceability and authentication in agri-food production: a multivariate approach to the characterization of the Italian food excellence elephant garlic (Allium ampeloprasum L.), a vasoactive nutraceutical

A research platform for food authentication was set up by combining stable isotope ratio analysis, metabolomics by gas and liquid mass-spectrometry and NMR investigations, chemometric analyses for food excellences. This multi-analytical approach was tested on samples of elephant garlic (Allium ampeloprasum L.), a species belonging to the same genus of common garlic (Allium ampeloprasum L.), mainly produced in southern Tuscany-(Allium ampeloprasum). The isotopic composition allowed the product to be geographically characterized. Flavonoids, like (+)-catechin, cinnamic acids, quercetin glycosides were identified. The samples showed also a significant amount of dipeptides, sulphur-containing metabolites and glutathione, the latter of which could be considered a molecular marker of the analyzed elephant garlic. For nutraceutical profiling to reach quality labels, extracts were investigated in specific biological assays, displaying interesting vasorelaxant properties in rat aorta by mediating nitric oxide release from the endothelium and exhibited positive inotropic and negative chronotropic effects in rat perfused hear

Scénario n.10. Un laboratoire pour un nouveau centre de consommation sur l'île de Hoffman, New York (USA)

Le projet s'inscrit dans la continuité d'une recherche théorique au sujet du système de consommation et de son implosion, telle que Baudrillard l'avait décrite: il utilise la même logique du systématique et l'alimente à tel point que le paradigme se change. L'île abandonnée de Hoffman Island dans la Lower Bay à New York donne le prétexte pour analyser les noyaux critiques du mall. Le choix stratégique de l'implantation permet une approche expérimentale et à la fois libérée du contexte: un laboratoire architectural et social. Le programme est composé par éléments hétérogènes qui se formalisent dans un seul volume hybride qui permet de révéler les contrastes entre le domaine de la consommation et sa conséquence, les déchets. Le projet propose une structure qui abrite une activité commerciale et un centre de recyclage des déchets produits par le centre même. L'objectif est de montrer le processus de la consommation de façon métabolique et de donner vie à un autre produit à partir des déchets. Tout ce qui est produit par le shopping mall est réintroduit dans le bâtiment, soit sous forme d'énergie, soit sous forme de produit. La plupart des déchets est composée de carton d'emballage et de papier qui deviennent la matière première pour concrétiser l'implosion. L'espace commercial se substitue peu à peu pour laisser place à l'archivage des livres produits avec ses déchets dans un processus dynamique et chronologique. Dans cette logique, plus le centre commercial consomme, plus il est attractif, plus il a du succès, plus il va produire de déchets et plus il est consumé. Le projet proposé invite à réfléchir sur l'instabilité et les contrastes en touchant les points faibles du centre commercial, en bouleversant le monde bruyant, attractif et pop du shopping mall, et en l'entraînant au moyen de ses propres cendres dans le monde du silence, du discret. Le mall apparait comme un vestige, une ruine pop du XXIe siècle qui vise à interpeller, à révéler, à faire prendre conscience

Production of bio-diesel from macro-algae of the Orbetello lagoon by various extraction methods

In the last few years, there has been a significant increase in finding alternative energy sources to fossil fuel. Bio-diesel derived from vegetable oils has been shown to be a potential alternative. Presently, most of the available bio-diesel is made from edible oils, but it is believed that with a large-scale production of bio-diesel these stocks may cause an imbalance to the food supply. Algae and aquatic bio-mass have the potential to provide a new range of third generation bio-fuels. Recently, there has been substantial increase in attention to the possibility of using aquatic bio-mass. The aim of this study was to evaluate the macro-algae oil yield and lipid composition in order to produce bio-diesel from waste bio-mass. The algal bio-mass comes from the Orbetello lagoon (Southern Tuscany, Italy), where macro-algae grow naturally due to eutrophication and are harvested and stored in a landfill as a special waste product. Lipid extraction was carried out according to the Bligh and Dyer method and also by using a Dionex ASE200 (accelerated solvent extractor). The total lipid content was determined by micro-gravimetry and the fatty acids (FAs) by GC-FID and GC-MS after acid transesterification. Chaetomorpha linum was the most abundant species and had the highest lipid content. Lipid concentrations and profiles of the Orbetello lagoon's macro-algae were comparable with those reported in the literature for the same species or genus. Algal FAs corresponded to those that normally constitute bio-diesel. Thus, the results indicate that bio-diesel could be produced from the harvested algal bio-mass. © 2013 Taylor & Francis

Antimicrobial activity against Helicobacter pylori strains and antioxidant properties of blackberry leaves (Rubus ulmifolius) and isolated compounds

8noRubus spp. (Rosaceae) provide extracts used in traditional medicine as antimicrobial, anticonvulsant, muscle relaxant and radical scavenging agents. Resistance to antibiotics used to treat Helicobacter pylori infection as well as their poor availability in developing countries prompted us to test the antimicrobial activity of Rubus ulmifolius leaves and isolated polyphenols against two H. pylori strains with different virulence (CagA+ strain 10K and CagA(-) strain G21). The antioxidant activity (TEAC values) of the tested compounds ranged from 4.88 (gallic acid) to 1.60 (kaempferol), whilst the leaf extract gave a value of 0.12. All the isolated polyphenols as well as the leaf extract showed antibacterial activity against both of the H. pylori strains. The minimum bactericidal concentrations (MBCs) of the extract for H. pylori strains G21 and 10K, respectively, were 1200 microg/mL and 1500 microg/mL after 24h of exposure and 134 microg/mL and 270 microg/mL after 48 h exposure. Ellagic acid showed very low MBC values towards both of the H. pylori strains after 48 h (2 microg/mL and 10 microg/mL for strains G21 and 10K, respectively) and kaempferol toward G21 strain (MBC=6 microg/mL). A relationship between antimicrobial activity and antioxidant capacity was found only for H. pylori strain G21 CagA(-) strain.reservedmixedMartini, Silvia; D'Addario, C.; Colacevich, Andrea; Focardi, Silvia; Borghini, Francesca; Santucci, Annalisa; Figura, Natale; Rossi, ClaudioMartini, Silvia; D'Addario, C.; Colacevich, Andrea; Focardi, Silvia; Borghini, Francesca; Santucci, Annalisa; Figura, Natale; Rossi, Claudi