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La Jolla, CA, United States

Fortunati E.,University of Perugia | Armentano I.,University of Perugia | Zhou Q.,KTH Royal Institute of Technology | Iannoni A.,University of Perugia | And 8 more authors.
Carbohydrate Polymers | Year: 2012

Nanocomposite films were prepared by the addition of cellulose nanocrystals (CNCs) eventually surfactant modified (s-CNC) and silver (Ag) nanoparticles in the polylactic acid (PLA) matrix using melt extrusion followed by a film formation process. Multifunctional composite materials were investigated in terms of morphological, mechanical, thermal and antibacterial response. The nanocomposite films maintained the transparency properties of the PLA matrix. Thermal analysis showed increased values of crystallinity in the nanocomposites, more evident in the s-CNC based formulations that had the highest tensile Young modulus. The presence of surfactant favoured the dispersion of cellulose nanocrystals in the polymer matrix and the nucleation effect was remarkably enhanced. Moreover, an antibacterial activity against Staphylococcus aureus and Escherichia coli cells was detected for ternary systems, suggesting that these novel nanocomposites may offer good perspectives for food packaging applications which require an antibacterial effect constant over time. © 2011 Elsevier Ltd. All rights reserved. Source

Rapposelli S.,University of Pisa | Coi A.,Consortium for Science and Technology of Materials | Imbriani M.,Fondazione S. Maugeri | Bianucci A.M.,University of Pisa | Bianucci A.M.,ICB International
International Journal of Molecular Sciences | Year: 2012

P-glycoprotein (P-gp) is an efflux pump involved in the protection of tissues of several organs by influencing xenobiotic disposition. P-gp plays a key role in multidrug resistance and in the progression of many neurodegenerative diseases. The development of new and more effective therapeutics targeting P-gp thus represents an intriguing challenge in drug discovery. P-gp inhibition may be considered as a valid approach to improve drug bioavailability as well as to overcome drug resistance to many kinds of tumours characterized by the over-expression of this protein. This study aims to develop classification models from a unique dataset of 59 compounds for which there were homogeneous experimental data on P-gp inhibition, ATPase activation and monolayer efflux. For each experiment, the dataset was split into a training and a test set comprising 39 and 20 molecules, respectively. Rational splitting was accomplished using a sphere-exclusion type algorithm. After a two-step (internal/external) validation, the best-performing classification models were used in a consensus predicting task for the identification of compounds named as "true" P-gp inhibitors, i.e., molecules able to inhibit P-gp without being effluxed by P-gp itself and simultaneously unable to activate the ATPase function. © 2012 by the authors; licensee MDPI, Basel, Switzerland. Source

Scudder S.L.,University of California at San Diego | Goo M.S.,University of California at San Diego | Cartier A.E.,ICB International | Molteni A.,University of California at San Diego | And 3 more authors.
Journal of Neuroscience | Year: 2014

The trafficking of AMPA receptors (AMPARs) to and from synapses is crucial for synaptic plasticity. Previous work has demonstrated that AMPARs undergo activity-dependent ubiquitination by the E3 ubiquitin ligase Nedd4-1, which promotes their internalization and degradation in lysosomes. Here, we define the molecular mechanisms involved in ubiquitination and deubiquitination of AMPARs. We report that Nedd4-1 is rapidly redistributed to dendritic spines in response to AMPAR activation and not in response to NMDA receptor (NMDAR) activation in cultured rat neurons. In contrast, NMDAR activation directly antagonizes Nedd4-1 function by promoting the deubiquitination of AMPARs. We show that NMDAR activation causes the rapid dephosphorylation and activation of the deubiquitinating enzyme (DUB) USP8. Surface AMPAR levels and synaptic strength are inversely regulated by Nedd4-1 and USP8. Strikingly, we show that homeostatic downscaling of synaptic strength is accompanied by an increase and decrease in Nedd4-1 and USP8 protein levels, respectively. Furthermore, we show that Nedd4-1 is required for homeostatic loss of surface AMPARs and downscaling of synaptic strength. This study provides the first mechanistic evidence for rapid and opposing activity-dependent control of a ubiquitin ligase and DUB at mammalian CNS synapses. We propose that the dynamic regulation of these opposing forces is critical in maintaining synapses and scaling them during homeostatic plasticity. © 2014 the authors. Source

Visai L.,University of Pavia | Visai L.,ICB International | de Nardo L.,Polytechnic of Milan | Punta C.,Polytechnic of Milan | And 3 more authors.
International Journal of Artificial Organs | Year: 2011

Titanium oxide is a heterogeneous catalyst whose efficient photoinduced activity, related to some of its allotropic forms, paved the way for its widespread technological use. Here, we offer a comparative analysis of the use of titanium oxide as coating for materials in biomedical devices. First, we introduce the photoinduced catalytic mechanisms of TiO 2 and their action on biological environment and bacteria. Second, we overview the main physical and chemical technologies for structuring suitable TiO 2 coatings on biomedical devices. We then present the approaches for in vitro characterization of these surfaces. Finally, we discuss the main aspects of TiO 2 photoactivated antimicrobial activity on medical devices and limitations for these types of applications. © 2011 The Authors. Source

Mtango N.R.,ICB International | Latham K.E.,Michigan State University | Sutovsky P.,University of Missouri
Advances in Experimental Medicine and Biology | Year: 2014

Post-translational modifications of cellular proteins by ubiquitin and ubiquitin-like protein modifiers are important regulatory events involved in diverse aspects of gamete and embryo physiology including oocyte maturation, fertilization and development of embryos to term. Deubiquitinating enzymes (DUBs) regulate proteolysis by reversing ubiquitination, which targets proteins to the 26S proteasome. The ubiquitin C-terminal hydrolases (UCHs) comprise are DUBs that play a role in the removal of multi-ubiquitin chains. We review here the roles of UCHs in oocytes maturation, fertilization and development in mouse, bovine, porcine and rhesus monkeys. Oocyte UCHs contributes to fertilization and embryogenesis by regulating the physiology of the oocyte and blastomere cortex as well as oocyte spindle. Lack of UCHs in embryos reduces fertilization, while mutant embryos fail to undergo compaction and blastocyst formation. In addition to advancing our understanding of reproductive process, research on the role of deubiquitinating enzymes will allow us to better understand and treat human infertility, and to optimize reproductive performance in agriculturally important livestock species. © 2014 Springer Science+Business Media New York. Source

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