Nanoparticles exposing neurotensin tumor-specific drivers

Nanoparticles have attracted much attention for their potential application as in vivo carriers of drugs. Labeling of nanoparticles with bioactive markers that are able to direct them toward specific biological target receptors has led to a new generation of drug delivery systems. In particular, low molecular weight peptides that remain stable in vivo could be promising tools to selectively drive nanoparticles loaded with active components to tumor cells. We reported, recently, that tetrabranched neurotensin peptides (NT4) may be used to selectively target tumor cells with liposomes. Liposomes functionalized with tetrabranched neurotensin peptide, NT4, and loaded with doxorubicin showed clear advantages in cell binding, anthracyclin internalization, and cytotoxicity in respect of not functionalized liposomes. In this study, we compare branched (NT4) versus linear (NT) peptides in the ability to drive liposomes to target cells and deliver their toxic cargo. We showed here that the more densely decorated liposomes had a better activity profile in terms of drug delivery. Presentation of peptides to the cell membranes in the grouped shape provided by branched structure facilitates liposome cell binding and fusion

A hierarchical Bayesian model for inference of copy number variants and their association to gene expression

A number of statistical models have been successfully developed for the analysis of high-throughput data from a single source, but few methods are available for integrating data from different sources. Here we focus on integrating gene expression levels with comparative genomic hybridization (CGH) array measurements collected on the same subjects. We specify a measurement error model that relates the gene expression levels to latent copy number states which, in turn, are related to the observed surrogate CGH measurements via a hidden Markov model. We employ selection priors that exploit the dependencies across adjacent copy number states and investigate MCMC stochastic search techniques for posterior inference. Our approach results in a unified modeling framework for simultaneously inferring copy number variants (CNV) and identifying their significant associations with mRNA transcripts abundance. We show performance on simulated data and illustrate an application to data from a genomic study on human cancer cell lines.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS705 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients

Temporal lobe epilepsy (TLE) is the most common type of partial epilepsy referred for surgery due to antiepileptic drug (AED) resistance. A common molecular target for many of these drugs is the voltage-gated sodium channel (VGSC). The VGSC consists of four domains of pore-forming α-subunits and two auxiliary β-subunits, several of which have been well studied in epileptic conditions. However, despite the β4-subunits’ role having been reported in some neurological conditions, there is little research investigating its potential significance in epilepsy. Therefore, the purpose of this work was to assess the role of SCN4β in epilepsy by using a combination of molecular and bioinformatics approaches. We first demonstrated that there was a reduction in the relative expression of SCN4B in the drug-resistant TLE patients compared to non-epileptic control specimens, both at the mRNA and protein levels. By analyzing a co-expression network in the neighborhood of SCN4B we then discovered a linkage between the expression of this gene and K+ channels activated by Ca2+, or K+ two-pore domain channels. Our approach also inferred several potential effector functions linked to variation in the expression of SCN4B. These observations support the hypothesis that SCN4B is a key factor in AED-resistant TLE, which could help direct both the drug selection of TLE treatments and the development of future AED

Neurotensin receptor 1 facilitates intracellular and transepithelial delivery of macromolecules

G protein-coupled receptors are expressed on the surface of eukaryotic cells and internalise in response to ligand binding. The actions of the hormone and neurotransmitter neurotensin (NT) are predominantly mediated by specific interactions with one such receptor. Neurotensin receptor 1 (NTS1), which is upregulated in a variety of cancers, including pancreatic and breast tumours. NTS1 could therefore serve as a target for selective delivery of therapeutics. This study characterised the expression of NTS1 in HEK293 cells, as well as both polarised and non-polarised intestinal epithelial Caco-2 cells. NT-conjugated fluorophores were internalised in NTS1-expressing HEK293 and Caco-2 cells in a receptor-mediated fashion. Confocal microscopy revealed fluorophore localisation in the perinuclear region. Cell uptake and transport across the Caco-2 intestinal model of two NT-conjugated fluorophores (GFP and fluorescein) were compared to evaluate the effect of cargo size on cellular uptake. This work demonstrates that NT ligand conjugation is able to deliver relatively large macromolecular cargoes selectively into cells overexpressing NTS1 and the system is able to effectively translocate macromolecules across an intestinal epithelial model. NTS1 therefore shows potential as a drug delivery target not only for targeted but also non-invasive (oral) delivery of biotherapeutics for cancer

Miglioramento della sicurezza per l'accessibilita al centro abitato di Porto Ercole (GR)

Sostituzione di due intersezioni a raso con due rotatorie gemelle in modo da rendere più fluidi i flussi di traffico e diminuire il tasso di incidentalità

Studio del mercato e dei trend del settore Automotive con particolare interesse sui Laboratori di ricerca a livello internazionale e impostazione di una strategia vincente per lo start-up e sviluppo del laboratorio di ricerca COMPOLAB di Livorno

Il lavoro riguarda l'analisi del Laboratorio di ricerca automotive CompoLab situato a Livorno. Il lavoro è sviluppato secondo la tecnica della formula imprenditoriale, ovvero una strategia risulta vincente se coerenti sono tra loro le variabili: azienda (ovvero le competenze distintive), il mercato di riferimento e il prodotto offerto. Per cui nella prima parte è stato analizzato il mercato automotive e le sue esigenze, focalizzandosi su i distretti tecnologici, ovvero realtà dove l'innovazione e il contenuto tecnologico sono elevati. In seguito è stato analizzato il comparto automotive livornese individuandone le criticità e le possibili soluzioni e da questo l'esigenza di creare una struttura in grado di incrementare la competitività del territorio (Compolab). Sono state descritte le competenze distintive individuate per il laboratorio e di conseguenza i servizi che è in grado di offrire. Le competenze distintive principalmente sono la validazione virtuale (analisi delle tolleranze di superfici, analisi del rumore e reverse engineering)e la progettazione avanzata. Dall'analisi risulta che le tre variabili sono coerenti tra loro, per cui la strategia di per se è vincente; da ciò è stato possibile concludere che il laboratorio è in grado di crescere e autososteners