37 research outputs found

    STUDIO IN VIVO E MODELLIZZAZIONE DELLA BIOMECCANICA DI UN ESEMPLARE DI OCTOPUS VULGARIS

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    Obiettivo e risultato dello studio è una prima determinazione di nuovi parametri oggettivi utili ad arricchire le conoscenze biologiche sull’Octopus vulgaris, sia in termini di performance che riguardo le strategie di controllo, e a definire linee guida per la progettazione e gestione di tecnologie bioispirate octopus-like a partire dall’osservazione diretta, ma non invasiva, di un esemplare della specie, con un’analisi delle sue proprietà e caratteristiche attraverso l’utilizzo di strumenti appositamente progettati ed un esame dei risultati attraverso una modellizzazzione. Attraverso tecniche di analisi e ricostruzione del movimento è stata ricostruita la cinematica e la dinamica del movimento attraverso propulsione. Con l’utilizzo di un opportuno setup video e di dispositivi progettati e realizzati ad hoc è stata condotta una caratterizzazione meccanica in vivo sul tentacolo, determinando il range di stretch longitudinale attivo. Con un altro setup strumentale, l'uso di sensori ed il supporto delle videocamere si sono determinate le performance di forza in trazione. Dalle prove di misura della forza è stata studiata la cinematica del movimento di roto-trazione adottato durante i tasks, valutando il contributo dei diversi fasci muscolari. I risultati del lavoro forniscono un esempio di come sia possibile ottenere parametri utili ed oggettivi, sia per la robotica che per la biologia, permettendo una crescita ed un’integrazione reciproca delle discipline

    GDF5 regulates TGFß-dependent angiogenesis in breast carcinoma MCF-7 cells: in vitro and in vivo control by anti-TGFß peptides

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    BACKGROUND: TGFß overproduction in cancer cells is one of the main characteristics of late tumor progression being implicated in metastasis, tumor growth, angiogenesis and immune response. We investigated the therapeutic efficacy of anti-TGFß peptides in the control of angiogenesis elicited by conditional over-expression of TGFß. METHODS: We have inserted in human MCF7 mammary-cancer cells a mutated TGFß gene in a tetracycline-repressible vector to obtain conditional expression of mature TGFß upon transient transfection, evaluated the signaling pathways involved in TGFß-dependent endothelial cells activation and the efficacy of anti-TGFß peptides in the control of MCF7-TGFß-dependent angiogenesis. RESULTS: TGFß over-expression induced in MCF7 several markers of the epithelial-to-mesenchymal transition. Conditioned-medium of TGFß-transfected MCF7 stimulated angiogenesis in vivo and in vitro by subsequent activation of SMAD2/3 and SMAD1/5 signaling in endothelial cells, as well as SMAD4 nuclear translocation, resulting in over-expression of the pro-angiogenic growth and differentiation factor-5 (GDF5). Inhibition or silencing of GDF5 in TGFß-stimulated EC resulted in impairment of GDF5 expression and of TGFß-dependent urokinase-plasminogen activator receptor (uPAR) overproduction, leading to angiogenesis impairment. Two different TGFß antagonist peptides inhibited all the angiogenesis-related properties elicited in EC by exogenous and conditionally-expressed TGFß in vivo and in vitro, including SMAD1/5 phosphorylation, SMAD4 nuclear translocation, GDF5 and uPAR overexpression. Antagonist peptides and anti-GDF5 antibodies efficiently inhibited in vitro and in vivo angiogenesis. CONCLUSIONS: TGFß produced by breast cancer cells induces in endothelial cells expression of GDF5, which in turn stimulates angiogenesis both in vitro and in vivo. Angiogenesis activation is rapid and the involved mechanism is totally opposed to the old and controversial dogma about the AKL5/ALK1 balance. The GDF-dependent pro-angiogenic effects of TGFß are controlled by anti-TGFß peptides and anti-GDF5 antibodies, providing a basis to develop targeted clinical studies

    A model of anti-angiogenesis: differential transcriptosome profiling of microvascular endothelial cells from diffuse systemic sclerosis patients

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    The objective of this work was to identify genes involved in impaired angiogenesis by comparing the transcriptosomes of microvascular endothelial cells from normal subjects and patients affected by systemic sclerosis (SSc), as a unique human model disease characterized by insufficient angiogenesis. Total RNAs, prepared from skin endothelial cells of clinically healthy subjects and SSc patients affected by the diffuse form of the disease, were pooled, labeled with fluorochromes, and hybridized to 14,000 70 mer oligonucleotide microarrays. Genes were analyzed based on gene expression levels and categorized into different functional groups based on the description of the Gene Ontology (GO) consortium to identify statistically significant terms. Quantitative PCR was used to validate the array results. After data processing and application of the filtering criteria, the analyzable features numbered 6,724. About 3% of analyzable transcripts (199) were differentially expressed, 141 more abundantly and 58 less abundantly in SSc endothelial cells. Surprisingly, SSc endothelial cells over-express pro-angiogenic transcripts, but also show up-regulation of genes exerting a powerful negative control, and down-regulation of genes critical to cell migration and extracellular matrix-cytoskeleton coupling, all alterations that provide an impediment to correct angiogenesis. We also identified transcripts controlling haemostasis, inflammation, stimulus transduction, transcription, protein synthesis, and genome organization. An up-regulation of transcripts related to protein degradation and ubiquitination was observed in SSc endothelial cells. We have validated data on the main anti-angiogenesis-related genes by RT-PCR, western blotting, in vitro angiogenesis and immunohistochemistry. These observations indicate that microvascular endothelial cells of patients with SSc show abnormalities in a variety of genes that are able to account for defective angiogenesis
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