Valentina Cappello

Bio: Valentina Cappello is an academic researcher from Istituto Italiano di Tecnologia. The author has contributed to research in topics: Autophagy & Duchenne muscular dystrophy. The author has an hindex of 23, co-authored 56 publications receiving 7819 citations. Previous affiliations of Valentina Cappello include University of Catania & Nest Labs.

Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease.

Abstract: Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of β- galactosylceramidase enzymatic activity and by widespread accumulation of the cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells. Despite the wide use of Twitcher mice as experimental model for KD, the ultrastructure of this model is partial and mainly addressing peripheral nerves. More details are requested to elucidate the basis of the motor defects, which are the first to appear during KD onset. Here we use transmission electron microscopy (TEM) to focus on the alterations produced by KD in the lower motor system at postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30 mouse. We find mild effects on motorneuron soma, severe ones on sciatic nerves and very severe effects on nerve terminals and neuromuscular junctions at P30, with peripheral damage being already detectable at P15. Finally, we find that the gastrocnemius muscle undergoes atrophy and structural changes that are independent of denervation at P15. Our data further characterize the ultrastructural analysis of the KD mouse model, and support recent theories of a dying-back mechanism for neuronal degeneration, which is independent of demyelination.

Autophagy as a new therapeutic target in Duchenne muscular dystrophy

Abstract: A resolutive therapy for Duchene muscular dystrophy, a severe degenerative disease of the skeletal muscle, is still lacking. Because autophagy has been shown to be crucial in clearing dysfunctional organelles and in preventing tissue damage, we investigated its pathogenic role and its suitability as a target for new therapeutic interventions in Duchenne muscular dystrophy (DMD). Here we demonstrate that autophagy is severely impaired in muscles from patients affected by DMD and mdx mice, a model of the disease, with accumulation of damaged organelles. The defect in autophagy was accompanied by persistent activation via phosphorylation of Akt, mammalian target of rapamycin (mTOR) and of the autophagy-inhibiting pathways dependent on them, including the translation-initiation factor 4E-binding protein 1 and the ribosomal protein S6, and downregulation of the autophagy-inducing genes LC3, Atg12, Gabarapl1 and Bnip3. The defective autophagy was rescued in mdx mice by long-term exposure to a low-protein diet. The treatment led to normalisation of Akt and mTOR signalling; it also reduced significantly muscle inflammation, fibrosis and myofibre damage, leading to recovery of muscle function. This study highlights novel pathogenic aspects of DMD and suggests autophagy as a new effective therapeutic target. The treatment we propose can be safely applied and immediately tested for efficacy in humans.

Cholesterol reduction impairs exocytosis of synaptic vesicles.

Abstract: Cholesterol and sphingolipids are abundant in neuronal membranes, where they help the organisation of the membrane microdomains involved in major roles such as axonal and dendritic growth, and synapse and spine stability. The aim of this study was to analyse their roles in presynaptic physiology. We first confirmed the presence of proteins of the exocytic machinery (SNARES and Ca(v)2.1 channels) in the lipid microdomains of cultured neurons, and then incubated the neurons with fumonisin B (an inhibitor of sphingolipid synthesis), or with mevastatin or zaragozic acid (two compounds that affect the synthesis of cholesterol by inhibiting HMG-CoA reductase or squalene synthase). The results demonstrate that fumonisin B and zaragozic acid efficiently decrease sphingolipid and cholesterol levels without greatly affecting the viability of neurons or the expression of synaptic proteins. Electron microscopy showed that the morphology and number of synaptic vesicles in the presynaptic boutons of cholesterol-depleted neurons were similar to those observed in control neurons. Zaragozic acid (but not fumonisin B) treatment impaired synaptic vesicle uptake of the lipophilic dye FM1-43 and an antibody directed against the luminal epitope of synaptotagmin-1, effects that depended on the reduction in cholesterol because they were reversed by cholesterol reloading. The time-lapse confocal imaging of neurons transfected with ecliptic SynaptopHluorin showed that cholesterol depletion affects the post-depolarisation increase in fluorescence intensity. Taken together, these findings show that reduced cholesterol levels impair synaptic vesicle exocytosis in cultured neurons.

Effects of Cerium Oxide Nanoparticles on PC12 Neuronal-Like Cells: Proliferation, Differentiation, and Dopamine Secretion

Abstract: Purpose Oxidative stress has been found to play a key role in several diseases, that range from cancer to neurodegenerative disorders. Besides traditional anti-oxidant agents, in recent years much attention has been focused on nanotechnological solutions, including cerium oxide nanoparticles (nanoceria).

Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease.

Abstract: Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of β- galactosylceramidase enzymatic activity and by widespread accumulation of the cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells. Despite the wide use of Twitcher mice as experimental model for KD, the ultrastructure of this model is partial and mainly addressing peripheral nerves. More details are requested to elucidate the basis of the motor defects, which are the first to appear during KD onset. Here we use transmission electron microscopy (TEM) to focus on the alterations produced by KD in the lower motor system at postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30 mouse. We find mild effects on motorneuron soma, severe ones on sciatic nerves and very severe effects on nerve terminals and neuromuscular junctions at P30, with peripheral damage being already detectable at P15. Finally, we find that the gastrocnemius muscle undergoes atrophy and structural changes that are independent of denervation at P15. Our data further characterize the ultrastructural analysis of the KD mouse model, and support recent theories of a dying-back mechanism for neuronal degeneration, which is independent of demyelination.

of amyotrophic lateral sclerosis

Abstract: Background: Components of the innate immune complement system have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS); however, a comprehensive examination of complement expression in this disease has not been performed. This study therefore aimed to determine the expression of complement components (C1qB, C4, factor B, C3/C3b, C5 and CD88) and regulators (CD55 and CD59a) in the lumbar spinal cord of hSOD1 G93A mice during defined disease stages. Methods: hSOD1 G93A and wild-type mice were examined at four different ages of disease progression. mRNA and protein expression of complement components and regulators were examined using quantitative PCR, western blotting and ELISA. Localisation of complement components within lumbar spinal cord was investigated using immunohistochemistry. Statistical differences between hSOD1 G93A and wild-type mice were analysed using a two-tailed t-test at each stage of disease progression. Results: We found several early complement factors increased as disease progressed, whilst complement regulators decreased; suggesting overall increased complement activation through the classical or alternative pathways in hSOD1 G93A mice. CD88 was also increased during disease progression, with immunolocalisation demonstrating expression on motor neurons and increasing expression on microglia surrounding the regions of motor neuron death. Conclusions: These results indicate that local complement activation and increased expression of CD88 may contribute to motor neuron death and ALS pathology in the hSOD1 G93A mouse. Hence, reducing complement-induced

Soft Robotic Grippers.

Abstract: Advances in soft robotics, materials science, and stretchable electronics have enabled rapid progress in soft grippers. Here, a critical overview of soft robotic grippers is presented, covering different material sets, physical principles, and device architectures. Soft gripping can be categorized into three technologies, enabling grasping by: a) actuation, b) controlled stiffness, and c) controlled adhesion. A comprehensive review of each type is presented. Compared to rigid grippers, end-effectors fabricated from flexible and soft components can often grasp or manipulate a larger variety of objects. Such grippers are an example of morphological computation, where control complexity is greatly reduced by material softness and mechanical compliance. Advanced materials and soft components, in particular silicone elastomers, shape memory materials, and active polymers and gels, are increasingly investigated for the design of lighter, simpler, and more universal grippers, using the inherent functionality of the materials. Embedding stretchable distributed sensors in or on soft grippers greatly enhances the ways in which the grippers interact with objects. Challenges for soft grippers include miniaturization, robustness, speed, integration of sensing, and control. Improved materials, processing methods, and sensing play an important role in future research.

Dynamin, a membrane-remodelling GTPase

Abstract: Dynamin, the founding member of a family of dynamin-like proteins (DLPs) implicated in membrane remodelling, has a critical role in endocytic membrane fission events. The use of complementary approaches, including live-cell imaging, cell-free studies, X-ray crystallography and genetic studies in mice, has greatly advanced our understanding of the mechanisms by which dynamin acts, its essential roles in cell physiology and the specific function of different dynamin isoforms. In addition, several connections between dynamin and human disease have also emerged, highlighting specific contributions of this GTPase to the physiology of different tissues.

Soft matter with hard skin : From skin wrinkles to templating and material characterization

Abstract: The English-language dictionary defines wrinkles as "small furrows, ridges, or creases on a normally smooth surface, caused by crumpling, folding, or shrinking". In this paper we review the scientific aspects of wrinkling and the related phenomenon of buckling. Specifically, we discuss how and why wrinkles/buckles form in various materials. We also describe several examples from everyday life, which demonstrate that wrinkling or buckling is indeed a commonplace phenomenon that spans a multitude of length scales. We will emphasize that wrinkling is not always a frustrating feature (e.g., wrinkles in human skin), as it can help to assemble new structures, understand important physical phenomena, and even assist in characterizing chief material properties.