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Search Results: 1 - 10 of 13477 matches for " Mario Rosario Guarracino "
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The MetaboX library: building metabolic networks from KEGG database
Francesco Maiorano,Luca Ambrosino,Mario Rosario Guarracino
Quantitative Biology , 2014,
Abstract: In many key applications of metabolomics, such as toxicology or nutrigenomics, it is of interest to profile and detect changes in metabolic processes, usually represented in the form of pathways. As an alternative, a broader point of view would enable investigators to better understand the relations between entities that exist in different processes. Therefore, relating a possible perturbation to several known processes represents a new approach to this field of study. We propose to use a network representation of metabolism in terms of reactants, enzyme and metabolite. To model these systems it is possible to describe both reactions and relations among enzymes and metabolites. In this way, analysis of the impact of changes in some metabolites or enzymes on different processes are easier to understand, detect and predict. Results: We release the MetaboX library, an open source PHP framework for developing metabolic networks from a set of compounds. This library uses data stored in Kyoto Encyclopedia for Genes and Genomes (KEGG) database using its RESTful Application Programming Interfaces (APIs), and methods to enhance manipulation of the information returned from KEGG webservice. The MetaboX library includes methods to extract information about a resource of interest (e.g. metabolite, reaction and enzyme) and to build reactants networks, bipartite enzyme-metabolite and unipartite enzyme networks. These networks can be exported in different formats for data visualization with standard tools. As a case study, the networks built from a subset of the Glycolysis pathway are described and discussed. Conclusions: The advantages of using such a library imply the ability to model complex systems with few starting information represented by a collection of metabolites KEGG IDs.
Rigidity and flexibility in protein-protein interaction networks: a case study on neuromuscular disorders
Ankush Sharma,Maria Brigida Ferraro,Francesco Maiorano,Francesca Del Vecchio Blanco,Mario Rosario Guarracino
Quantitative Biology , 2014,
Abstract: Mutations in proteins can have deleterious effects on a protein's stability and function, which ultimately causes particular diseases. Genetically inherited muscular dystrophies (MDs) include several genetic diseases, which cause increasing weakness in muscles and disability to perform muscular functions progressively. Different types of mutations in the gene coding translates into defunct proteins cause different neuro-muscular diseases. Defunct protein interactions in human proteome may cause a stress to its neighboring proteins and its modules. We therefore aimed to understand the effects of mutated proteins on interacting partners in different muscular dystrophies utilizing network biology to understand system properties of these MDs subnetworks .We investigated rigidity and flexibility of protein-protein interaction subnetworks associated with causative mutated genes showing high mean interference values in muscular dystrophy. Rigid component related to EEF1A1 subnetwork and members of 14.3.3 protein family formed the core of network showed involvement in molecular function related to protein domain specific binding. CACNA1S and CALM1 showing functionality related to Voltage-dependent calcium channel demonstrated highest flexibility. The interconnected subnets of proteins corresponding to known causative genes having large genetic variants are shared in different muscular dystrophies inferred towards comorbidity in diseases. The studies demonstrates core network of MDs as highly rigid, constituting of large intermodular edges and interconnected hub nodes suggesting high information transfer flow. The core skeleton of the network is organized in protein specific domain binding. This suggests neuro-muscular disorders may initiate due to interruption in molecular function related with the core and its aggression may depend on the tolerance level of the networks.
Prediction of the responsiveness to pharmacological chaperones: lysosomal human alpha-galactosidase, a case of study
Giuseppina Andreotti, Mario R Guarracino, Marco Cammisa, Antonella Correra, Maria Cubellis
Orphanet Journal of Rare Diseases , 2010, DOI: 10.1186/1750-1172-5-36
Abstract: We collected the experimental data available in literature on the enzymatic activity of ninety-six missense mutants of lysosomal alpha-galactosidase measured in the presence of pharmacological chaperones. We associated with each mutation seven features derived from the analysis of 3D-structure of the enzyme, two features associated with their thermo-dynamic stability and four features derived from sequence alone. Structural and thermodynamic analysis explains why some mutants of human lysosomal alpha-galactosidase cannot be rescued by pharmacological chaperones: approximately forty per cent of the non responsive cases examined can be correctly associated with a negative prognostic feature. They include mutations occurring in the active site pocket, mutations preventing disulphide bridge formation and severely destabilising mutations. Despite this finding, prediction of mutations responsive to pharmacological chaperones cannot be achieved with high accuracy relying on combinations of structure- and thermodynamic-derived features even with the aid of classical and state of the art statistical learning methods.We developed a procedure to predict responsive mutations with an accuracy as high as 87%: the method scores the mutations by using a suitable position-specific substitution matrix. Our approach is of general applicability since it does not require the knowledge of 3D-structure but relies only on the sequence.Responsiveness to pharmacological chaperones depends on the structural/functional features of the disease-associated protein, whose complex interplay is best reflected on sequence conservation by evolutionary pressure. We propose a predictive method which can be applied to screen novel mutations of alpha galactosidase. The same approach can be extended on a genomic scale to find candidates for therapy with pharmacological chaperones among proteins with unknown tertiary structures.Pharmacological chaperone (PC) therapy has been recently proposed as a promising
L'unificazione nazionale e l’eccezionalità italiana / The National Unification and the Italian Exception
Guarracino, Scipione
Storicamente , 2011,
Abstract:
The Dance of the Dead Rhino: William Kentridge’s Magic Flute
Serena Guarracino
Altre Modernità , 2010,
Abstract: The article offers a reading of the staging of The Magic Flute by visual artist William Kentridge, focusing on his introduction of the rhino in the visual landscape of the opera as symbol for the silenced subject of violence. Operatic tradition has always been concerned with the staging of death, in particular with the death of its female protagonists, and recent scholarship has highlighted the complicity of the genre with the ideology of Western patriarchy and colonial violence. In this light, Kentridge's appropriation stages Mozart's opera as both voice of colonial Europe and place of resistance for the postcolonial artist. Kentridge moves the setting of the opera to colonial Africa, and the Flute becomes haunted with the massacre of the Herero people in South West Africa by the German army led by general von Trotha (1904-1907). The African white rhino, a species under the threat of extinction, works in this work as proxy for the missing corpses of the Herero people; in its being subject to humiliation and ruthless murder, it recalls Judith Butler's recent attempt at a different categorization of human life as both a continuous exposure to violence and what can be mourned after death. With its silence among the powerful sounds of Mozart's opera, the body of the dead, dancing rhino stands at the centre of Kentridge's work, which becomes a ceremony of mourning where the Western canon can be made to "resonate differently" (Trinh T. Minh-ha).
Striatal Signaling in L-DOPA-Induced Dyskinesia: Common Mechanisms with Drug Abuse and Long Term Memory Involving D1 Dopamine Receptor Stimulation
Mario Gustavo Murer,Rosario Moratalla
Frontiers in Neuroanatomy , 2011, DOI: 10.3389/fnana.2011.00051
Abstract: Parkinson’s disease is a common neurodegenerative disorder caused by the degeneration of midbrain substantia nigra dopaminergic neurons that project to the striatum. Despite extensive investigation aimed at finding new therapeutic approaches, the dopamine precursor molecule, 3,4-dihydroxyphenyl-L-alanine (L-DOPA), remains the most effective and commonly used treatment. However, chronic treatment and disease progression lead to changes in the brain’s response to L-DOPA, resulting in decreased therapeutic effect and the appearance of dyskinesias. L-DOPA-induced dyskinesia (LID) interferes significantly with normal motor activity and persists unless L-DOPA dosages are reduced to below therapeutic levels. Thus, controlling LID is one of the major challenges in Parkinson’s disease therapy. LID is the result of intermittent stimulation of supersensitive D1 dopamine receptors located in the very severely denervated striatal neurons. Through increased coupling to Gαolf, resulting in greater stimulation of adenylyl-cyclase, D1 receptors phosphorylate DARPP-32, and other protein kinase A targets. Moreover, D1 receptor stimulation activates extracellular signal-regulated kinase and triggers a signaling pathway involving mammalian target for rapamycin and modifications of histones that results in changes in translation, chromatin modification, and gene transcription. In turn, sensitization of D1 receptor signaling causes a widespread increase in the metabolic response to D1 agonists and changes in the activity of basal ganglia neurons that correlate with the severity of LID. Importantly, different studies suggest that dyskinesias may share mechanisms with drug abuse and long term memory involving D1 receptor activation. Here we review evidence implicating D1 receptor signaling in the genesis of LID, analyze mechanisms that may translate enhanced D1 signaling into dyskinetic movements, and discuss the possibility that the mechanisms underlying LID are not unique to the Parkinson’s disease brain.
Implementing a simple vectorial bridge with a digital oscilloscope
Rosario Bartiromo,Mario De Vincenzi
Physics , 2013, DOI: 10.1119/1.4891655
Abstract: We show how to exploit instrumentation available in undergraduate student laboratories to build a simple vectorial bridge. In particular we take advantage from the possibility to read data from a digital oscilloscope with a personal computer and describe an algorithm to obtain an accurate evaluation of the phase difference between two sinusoidal signals. The use of the bridge to characterize components of a high Q RLC filter is shown to greatly improve the understanding of results in resonance experiments. Direct evidence of dielectric losses, of skin currents and of the effect of distributed capacitance is obtained.
An Analytical Approach to the Analysis of Inhomogeneous Pipes under External Pressure
Massimiliano Fraldi,Federico Guarracino
Journal of Applied Mathematics , 2012, DOI: 10.1155/2012/134896
Abstract: Pipes for deep-water applications possess a diameter-to-thickness ratio in a region where failure is dominated by both instability and plastic collapse. This implies that prior to failure the compressive yield strength of the material must be exceeded, followed by ovalisation and further local yielding. This paper presents an investigation into the mechanics of this specific problem and develops an analytical approach that accounts for the effects of geometrical and material data on the collapse pressure of inhomogeneous rings under external hydrostatic pressure. The analytical expressions have been correlated to numerical and experimental test data, proving their accuracy.
Diophantine approximations and convergence of series in Banach spaces
Giovanni Fiorito,Rosario Musmeci,Mario Strano
Le Matematiche , 1993,
Abstract: n this paper we give a new proof of a known diophantine approximation result, then we apply this to prove convergence of a class of series in a Banach space, whose terms are defined recursively.
Sulle serie il cui termine generale è definito per ricorrenza
Giovanni Fiorito,Rosario Musmeci,Mario Strano
Le Matematiche , 1991,
Abstract: In this paper we prove some theorems that emphasize properties of the series whose terms are defined recursively. Suitable examples and counter-examples complete the theory.
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