87,013 research outputs found

    Stellato Marcello Palingenio

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    biografia scientifica di Marcello Palingenio Stellato e ricostruzione dei contenuti dello Zodiacus vita

    X-ray absorption spectroscopy: a powerful tool for structural studies of molecules involved in the pathogenesis of neurodegenerative diseases

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    Questa tesi descrive l’applicazione della spettroscopia di assorbimento dei raggi X allo studio di sistemi biologici che sono particolarmente interessanti per la loro rilevanza biomedica. Si usa una combinazione della XAS e di altre tecniche sperimentali per studiare tre classi di molecole (i peptidi Aβ, la proteina prionica e la neuromelanina) coinvolte nella patogenesi delle malattie neurodegenerative. I peptidi Aβ sono la principale componente delle placche amiloidi, che costituiscono una delle lesioni caratteristiche osservate nel cervello dei malati di Alzheimer. È stato osservato che le placche amiloidi contengono elevate concentrazioni di ioni metallici quali Cu e Zn. Si effettuano misure di densità ottica, di spettroscopia infrarossa in trasformata di Fourier e di XAS per determinare la struttura atomica locale dei siti di legame dei metalli. Gli esperimenti mostrano che Cu e Zn hanno ruoli diversi nel processo di aggregazione, ed in particolare che lo Zn è più efficace del Cu nel promuoverla. La proteina prionica è coinvolta nella patogenesi di una classe di malattie neurodegenerative infettive. In particolare, la conversione di questa proteina dalla sua forma normale alla cosiddetta forma scrapie causa l’enecefalopatia spongiforme trasmissibile. Si è osservato che la regione N-terminale della proteina prionica ha un’elevata affinità per metalli quali Cu e Zn. Gli esperimenti XAS descritti in questa tesi mostrano che il modo di coordinazione del Cu dipende dalla presenza di ioni Zn e che, pur non essendo lo Zn in grado di rimuovere il Cu legato alla proteina, è in grado di modificarne il modo di coordinazione. La neuromelanina è una molecola che si accumula nei neuroni soggetti a processi neurodegenerativi nelle persone affette dalla malattia di Parkinson. La XAS è qui utilizzata per studiare la coordinazione dello zolfo nella neuromelanina umana, in alcune melanine sintetiche ed in due composti modello contenenti zolfo, la cisteina ed il tricocromo C. Sulla base di fit della neuromelanina umana e delle melanine sintetiche in termini dei composti modello, si riconosce la presenza di modi di coordinazione dello zolfo simili a quelli sia della cisteina, sia del tricocromo, e si quantifica la loro abbondanza relativa. Infine, la XAS è utilizzata per studiare un problema non connesso alla patogenesi di una malattia neurodegenerativa, ovvero la mancanza di prolidasi. La prolidasi umana è un enzima importante nelle fasi finali del metabolismo delle proteine, e la sua carenza o il suo mancato funzionamento sono alla base di una grave malattia. Nel presente tesi si usa la XAS per determinare il sito di legame di Mn e Zn, mostrando la presenza di un sito di legame dimetallico nella forma attiva della proteina.This thesis describes the application of the X-ray Absorption Spectroscopy (XAS) to the study of biological systems that are particularly interesting for their biomedical role. Three classes of molecules, namely the Aβ peptides, the prion protein and the neuromelanin, which are related to the pathogenesis of neurodegenerative diseases, are studied by using a combination of XAS and other experimental techniques. Aβ peptides aggregates are the main component of the amyloid plaques, which are a peculiar lesion found in Alzheimer’s disease brains. The plaques have been shown to contain increased concentration of transition metals like Cu and Zn. Sedimentation assays, Fourier Transform Infrared Spectroscopy and XAS are used to determine the atomic structure around the metal binding site in samples where Aβ peptides are in complex with either Cu or Zn ions. The experiments show that Cu and Zn play different roles, and that Zn is more effective than Cu in promoting peptides aggregation. The prion protein is related to the pathogenesis of a class of infectious, neurodegenerative diseases. In particular, the conversion of the prion protein from its normal cellular form to the so-called scrapie form is responsible for the transmissible spongiform encephalopathies, and it has been shown that the prion protein is able to bind Cu and Zn ions in its N-terminal octarepeat domain. The XAS experiments reported in this thesis show that the Cu binding mode depends on the presence of Zn ions and, even if Zn is not able to displace Cu, Zn is able to change the way Cu is bound to the prion protein. Neuromelanin is a complex molecule accumulating in the neurons that undergo a degenerative process in Parkinson’s Disease. XAS is employed to investigate the sulphur binding mode in natural human neuromelanin, in synthetic melanins and in certain structurally known model compounds, namely cysteine and trichochrome C. Based on comparative fits of human and synthetic neuromelanin spectra in terms of those of model compounds, the occurrence of both cysteine- and trichochrome-like sulphur coordination modes is recognized and the relative abundance of these two types of structural arrangement is determined. Finally, XAS is used to study a biomedical problem not connected to neurodegenerative diseases, that is the prolidase deficiency. Human prolidase is a metalloenzyme that is important in the latest stages of protein catabolism. XAS is employed here to obtain a structural characterization of the Mn and Zn binding sites and shows the existence of heterogeneous dimeric metallic sites in the active form of the protein

    A case study on possible radiological contamination in the Lo Uttaro landfill site (Caserta, Italy)

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    The prevention of radioactive pollution is a primary objective of environmental protection codes in the operation of solid waste landfill activities. Several studies have demonstrated the effectiveness of radiological monitoring of the main constituents of urban landfill waste. The present contribution reports on an investigation plan carried out to evaluate the possible radiological contamination in the municipal landfill Lo Uttaro, district of Caserta (Italy). The investigation focused primarily on the perimeter area of the landfill in order to assess the possible impact on the surrounding population. The results of measurements of the equivalent dose rate along the perimeter of the landfill show average values lower than the population dose limit due to natural background radiation. Several samples of soil, groundwater and leachate representative of the subsoil of the study area were collected and the radionuclides were measured by gamma spectrometry. The results of these measurements show the absence of artificial radionuclides, except for small amounts of 137Cs due to nuclear disasters occurring in the last 50 years on Earth, and the mere presence of 40K and other natural radionuclides belonging to natural radioactive chains of 238U, 235U and 232Th

    Migrating bibliographic datasets to the Semantic Web: The AGRIS case

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    AGRIS is among the most comprehensive online collections of agricultural and related sciences information. It is a growing global catalog of 5 million high-quality structured bibliographic records indexed from a worldwide group of providers. AGRIS relies heavily on the AGROVOC thesaurus for its indexing. Following the conversion of that thesaurus into a SKOS concept-scheme and its publication as Linked Open Data (LOD), the entire set of AGRIS records was also triplified and released as LOD. As part of this exercise, OpenAGRIS, a semantic mashup application, was developed to dynamically combine AGRIS data with external data sources, using a mixture of SPARQL queries and web services. The re-engineering of AGRIS for the Semantic Web raised numerous issues regarding the relative lack of administrative metadata required to compellingly address the proof and trust layers of the Semantic Web stack, both within the AGRIS repository and in the external data pulled into OpenAGRIS. The AGRIS team began a process of disambiguation and enrichment to continue moving toward an entity-based view of its resources, beginning with the tens of thousands of journals attached to its records. The evolution of the system, the issues raised during the triplification process and the steps necessary for publishing the result as LOD content are hereby discussed and evaluated

    The AGROVOC Linked Dataset

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    Born in the early eighties as a multilingual authority file of agricultural index terms, AGROVOC has steadily evolved these last thirty years, moving to an electronic version around the year 2000 and shortly thereafter embracing the Semantic Web. Today AGROVOC is a SKOS-XL concept scheme published as Linked Open Data cloud, containing links (as well as backlinks) and references to many other Linked Datasets in the LOD cloud. In this paper we provide a brief historical summary of AGROVOC and detail its specification as a Linked Dataset

    Semantic Turkey - A new Web experience in between ontology editing and semantic annotation

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    In this work we describe Semantic Turkey, a Semantic Extension for the popular web browser Mozilla Firefox. Semantic Turkey can be used to keep track of relevant information from visited web sites and organize collected content according to a personally defined ontology. In this sense, Semantic Turkey can be seen both as an advanced semantic bookmarking system as well as an ontology editing assistant, which allows domain experts and ontology developers to build ontologies starting from the very raw source of information which they find on the web. The open architecture of Semantic Turkey and the specific three-layered approach of its design also allows for scaling the basic personal desktop application embodied by this tool up to a distributed framework for collaborative semantic annotation and ontology editing. This paper describes the architecture and the functionalities of the Semantic Turkey extension for Firefox, and describe possible evolutions for future improvement of the tool

    The role of metals in amyloid aggregation: A test case for ab initio simulations

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    First principle ab initio molecular dynamics simulations of the Car-Parrinello type have proved to be of invaluable help in understanding the microscopic mechanisms of chemical bonding both in solid state physics and in structural biophysics. In this work we present as test cases the study of the Cu coordination mode in two especially important examples: Prion protein and beta-amyloids. Using medium size PC-clusters as well as larger parallel platforms, we are able to deal with systems comprising 300 to 500 atoms and 1000 to 1500 electrons for as long as 2 - 3 ps. We present structural results which confirm indications coming from NMR and XAS data
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