1,722,582 research outputs found
Stellato Marcello Palingenio
biografia scientifica di Marcello Palingenio Stellato e ricostruzione dei contenuti dello Zodiacus vita
Tibaldo L., Sotto un cielo stellato. Vita e morte di Nicola Sacco e Bartolomeo Vanzetti, pref. di Giuliano Montaldo, Claudiana, Torino 2008
Recensione del volume Tibaldo L., Sotto un cielo stellato. Vita e morte di Nicola Sacco e Bartolomeo Vanzetti, pref. di Giuliano Montaldo, Claudiana, Torino 200
Anice verde e anice stellato, toccasana per migliorare la digestione
Sia l’Anice verde che quello stellato sono impiegati come carminativi, stimolanti, blandi spasmolitici, deboli agenti antibatterici ed espettoranti, ma non solo..
X-ray absorption spectroscopy: a powerful tool for structural studies of molecules involved in the pathogenesis of neurodegenerative diseases
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
Posttranscriptional Gene Regulation: Novel Pathways for Glucocorticoids' Anti-inflammatory Action.
Posttranscriptional gene regulation
(PTR) is a fundamental biological process that
integrates with the master transcriptional control of
gene expression, in ways that only in the last decade
have been increasingly understood [1, 2]. While
epigenetic and transcriptional events shape cell
response qualitatively, deciding the pattern of gene
expression to ‘switch on or off’ in response to
endogenous or environmental triggers, the key task of
PTR is to act as a ‘rheostat’ and rapidly adapt the
cellular response by providing the appropriate
amplitude and timing to the protein expression patterns
[3, 4]. The pivotal role of this mechanism comes to the
forefront in inflammatory and immune response, where
the changes in amplitude and duration in the expression
of dangerous and protective genes are in delicate
balance, and are critical in determining either the
successful resolution of the immune response or its
chronic overexpression [5]. This brief review introduces
members of the main classes of molecules mediating the
cytoplasmic arm of gene regulation, namely RNAbinding proteins and micro-RNA (miRNA), and
summarizes experimental data that underscore the role
of these molecules in the pathophysiology of chronic
inflammation, as well as their promising value as
mechanisms conveying the anti-inflammatory effect of
synthetic glucocorticoids
Glucocorticoid actions on airway epithelial responses in immunity: Functional outcomes and molecular targets
Research on the biology of airway epithelium in the last decades has progressively uncovered the many roles of this cell type during the immune response. Far from the early view of the epithelial layer simply as a passive barrier, the airway epithelium is now considered a central player in mucosal immunity, providing innate mechanisms of first-line host defense as well as facilitating adaptive immune responses. Alterations of the epithelial phenotype are primarily involved in the pathogenesis of allergic airways disease, particularly in severe asthma. Appreciation of the epithelium as target of glucocorticoid therapy has also grown, because of studies defining the pathways and mediators affected by glucocorticoids, and studies illustrating the relevance of the control of the response from epithelium in the overall efficacy of topical and systemic therapy with glucocorticoids. Studies of the mechanism of action of glucocorticoids within the biology of the immune response of the epithelium have uncovered mechanisms of gene regulation involving both transcriptional and posttranscriptional events. The view of epithelium as therapeutic target therefore has plenty of room to evolve, as new knowledge on the role of epithelium in immunity is established and novel pathways mediating glucocorticoid regulation are elucidated
Dictionary, Thesaurus or Ontology? Disentangling Our Choices in the Semantic Web Jungle
The Semantic Web seems finally close to maintaining its promise about a real world-wide graph of interconnected resources. The SPARQL query language and protocols and the Linked Open Data initiative have laid the way for endless data endpoints sparse around the globe. However, for the Semantic Web to really happen, it does not suffice to get billions of triples out there: these must be shareable, interlinked and conform to widely accepted vocabularies. While more and more data are converted from already available large knowledge repositories of companies and organizations, the question whether these should be carefully converted to semantically consistent ontology vocabularies or find other shallow representations for their content naturally arises. The danger is to come up with massive amounts of useless data, a boomerang which could result to be contradictory for the success of the web of data. In this paper, I provide some insights on common problems which may arise when porting huge amount of existing data or conceptual schemes (very common in the agriculture domain) to resource description framwork (RDF), and will address different modeling choices, by discussing in particular the relationship between the two main modeling vocabularies offered by W3C: OWL and SKOS
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