292 research outputs found
identificazione e caratterizzazione di una nuova miopatia vacuolare causata da una mutazione nel gene PLIN4 e possibili strategie per lo sviluppo di una terapia
No full textIn una famiglia affetta da miopatia vacuolare distale abbiamo effettuato esoma genoma e RNAseq non riuscendo ad individuare varianti codificanti verosimilmente patogeniche.
Contemporaneamente, una paziente con una ricombinazione si è sottoposta a biopsia muscolare nella quale un’analisi immunistochimica ha mostrato un aumentato segnale a livello subsarcolemmale e all’interno dei vacuoli, di due proteine legate alla degradazione delle proteine misfolded e aggregate, p62/SQSTM1 e le proteine ubiqutinate (FK2).
La stessa analisi su pazienti con severità del fenotipo media o grave, ha mostrato una correlazione con l’intensità di queste marcature.
Pertanto abbiamo ipotizzato che la proteina che veniva marcata in maniera così specifica dovesse essere la nostra proteina mutata. Abbiamo quindi effettuato una microdissezione laser dei vacuoli con analisi di spettrometria di massa, evidenziando così che la proteina accumulata nei vacuoli e codificata dal gene PLIN4 presente sull’aplotipo comune, era perilipina 4.
Dalla rianalisi dei dati di NGS abbiamo individuato un picco di coverage compatibile con una possibile ripetizione della sequenza.
Un sequenziamento long-read usando la tecnologia Oxford Nanopore Technology, ha identificato una espansione di 9x99 nucleotidi nella regione dell’esone 3, codificante per il dominio anfipatico di perilipina-4, regione strutturalmente correlata alle eliche anfipatiche presenti in α-sinucleina e nelle apolipoproteine.
L’analisi immunoistochimica focalizzata sul pathway dell’aggreafgia, ha confermato che l’accumulo di perilipina-4 nel muscolo è associato all’attivazione di questo pathway, mediato dall’ubiquitinazione degli aggregati e deputato all’eliminazione degli stessi tramite autofagia.
Questa nuova patologia è quindi una malattia da accumulo di aggregati, causata da una espansione di una regione della proteina con apparente incapacità dell’aggrefagia stessa di controllarne l’accumulo.
Lo studio del meccanismo molecolare a livello cellulare, non è stato possibile nei mioblasti derivati da biopsie dei pazienti, in quanto questa proteina non risulta essere espressa a questo livello.
Pertanto, abbiamo deciso di generare un modello di overespressione nel quale la proteina mutata e quella wild-type verranno confrontate per validare la propensità della variante mutata a causare precipitazione di aggregati.In a family affected by distal vacuolar myopathy we performed genome exome and RNAseq, failing to identify probably pathogenic coding variants.
At the same time, a patient with a recombination underwent a muscle biopsy in which an immunohistochemical analysis showed an increased signal at the subsarcolemmal level and within the vacuoles, of two proteins linked to the degradation of the misfolded and aggregated proteins, p62 / SQSTM1 and ubiqutinated proteins (FK2).
The same analysis on patients with increasing severity of the phenotype showed a correlation with the intensity of these proteins’ signals.
Therefore, we hypothesized that the protein that was labeled so specifically must be our mutated protein. We then performed a laser microdissection of the vacuoles with mass spectrometry analysis, thus highlighting that the protein accumulated in the vacuoles and encoded by the PLIN4 gene present on the common haplotype, was perilipin 4.
From the re-analysis of the NGS data we identified a coverage peak compatible with a possible repetition of the sequence.
Long-read sequencing using Oxford Nanopore Technology identified an expansion of 9x99 nucleotides in the exon 3 region, encoding the amphipathic domain of perilipin-4, a region structurally related to the amphipathic helices present in α-synuclein and apolipoproteins.
The immunohistochemical analysis focused on the aggreaphagy pathway confirmed that the accumulation of perilipin-4 in the muscle is associated with the activation of this pathway, mediated by the ubiquitination of the aggregates and responsible for eliminating them through autophagy.
This new pathology is therefore an aggregate accumulation disease, caused by an expansion of a region of the protein with the apparent inability of the aggrephagy itself to control its accumulation.
The study of the molecular mechanism at the cellular level was not possible in myoblasts derived from patient biopsies, as this protein does not appear to be expressed at this level.
Therefore, we decided to generate an overexpression model in which the mutated and wild-type proteins will be compared to validate the propensity of the mutated variant to cause aggregate precipitation
Spectrum of skeletal abnormalities in a complex malformation syndrome with "cutis tricolor" (Ruggieri-Happle syndrome)
No full textBackground: The term cutis tricolor describes the combination of congenital hyper- and hypopigmented skin lesions in close proximity to each other in a background of normal complexion. This phenomenon has been reported: (i) as a purely cutaneous trait; (ii) as a part of a complex malformation syndrome (Ruggieri-Happle syndrome - RHS); (iii) as a distinct type [cutis tricolor parvimaculata]; (iv) in association with other (e.g. vascular) skin disturbances. Objectives: To delineate the spectrum of skeletal defects in cutis tricolor. Methods: Retrospective and prospective analysis of skeletal surveys in 14 subjects (eight men; six women; aged 2-28 years) with cutis tricolor [4 purely cutaneous trait; 10 syndromic (RHS)]. Results: Bone abnormalities were recorded in 71.4% (10/14) of patients [100% (10/10) of cases with (other-than-skeletal) extra-cutaneous manifestations vs. null (0/4) in cases with purely cutaneous traits] and included overall small skull (n = 6); prognathism (n = 6); 'J'-shaped pituitary fossa (n = 1); absence of atlas posterior arch (n = 3); frontal bossing (n = 6); scoliosis (n = 9) with kyphosis (n = 6) and/or lordosis (n = 6); vertebral (n = 9) and ribs (n = 4) defects. Negative ZFHX1B gene analyses excluded overlaps with Mowat-Wilson syndrome. Conclusions: Cutis tricolor may be a marker of underlying skeletal involvement particularly in subjects with a complex syndromic (RHS) phenotype. © 2010 The Author(s)/Acta Pædiatrica © 2010 Foundation Acta Pædiatrica
Studies for the Historical-Critical Analysis of a Historical Center. The Case Study of Castel Camponeschi
No full text[EN] Aim of the paper is the historical-critical study of Castel Camponeschi (aka Castello di Prata), a village
at about 25 km from L’Aquila city (Italy), with peculiar urban characteristics –a herringbone pattern–
probably founded in the thirteenth century and characterized by important phenomena of modification
and stratification. The study roots on the direct analysis of the built heritage through the architectural
surveying, realized at multiple scales from the urban settlement to the masonry structures. According to
the morphology of the historic center, it could be traced to the process of new settlement foundation that
characterized the territory –the border between the Papal State and the Frederic’s Empire first, and then
the Angevin kingdom–. The analysis of the village requires both a correlation with the natural and anthropic historical context in which it is inserted and, a specific study of masonry equipments, characterized by the re-used of stone elements from the nearby Vestino-Roman town of Peltuinum.Trizio, I.; Brusaporci, S.; Continenza, R.; Maiezza, P.; Tata, A.; Ruggieri, A.; Giannageli, A. (2020). Studi per l’analisi storico-critica di un centro storico. Il caso di studio di Castel Camponeschi. Editorial Universitat Politècnica de València. 1449-1456. https://doi.org/10.4995/FORTMED2020.2020.11444OCS1449145
Correlazioni tra l'inquinamento ambientale e la prevalenza di diabete mellito di tipo II
No full textChemical interaction, space-charge layer, and molecule charging energy for a TiO2/TCNQ interface
No full textThree driving forces control the energy level alignment between transition-metal oxides and organic materials: the chemical interaction between the two materials, the organic electronegativity, and the possible space charge layer formed in the oxide. This is illustrated in this study by analyzing experimentally and theoretically a paradigmatic case, the TiO2(110)/TCNQ interface; due to the chemical interaction between the two materials, the organic electron affinity level is located below the Fermi energy of the n-doped TiO2. Then, one electron is transferred from the oxide to this level and a space charge layer is developed in the oxide, inducing an important increase in the interface dipole and in the oxide work function.Peer reviewe
Authentication of PDO saffron of L'Aquila (Crocus sativus L.) by HPLC-DAD coupled with a discriminant multi-way approach
No full textOne hundred and forty-nine (149) Italian saffron samples produced in the years from 2013 to 2016 in distinct sites located in five different Italian regions, Abruzzo, Tuscany, Umbria, Campania and Sardinia, together with twenty-seven (27) commercial samples, have been analyzed by high-performance liquid chromatography with diode array detection (HPLC-DAD). Among the investigated samples, those produced in Abruzzo (L'Aquila area) present an even higher added-value, because, since 2005, saffron of L'Aquila has been granted of the protected designation of origin (PDO) mark. In the present study, two different analytical approaches aimed at distinguishing PDO saffron of L'Aquila from the other samples have been compared. The first strategy is a more traditional approach, where the chromatograms collected at specific wavelengths are classified by Partial Least Squares Discriminant Analysis (PLS-DA). The second strategy exploits the multi-way nature of data, avoiding discarding any source of information. Consequently, the entire spectro-chromatogram is handled by N-Partial Least Squares (N-PLS) and then classified by Linear Discriminant Analysis (LDA). Both approaches provided satisfactory predictions; the best results from the prediction point of view (estimated on an external set of samples) were achieved by the proposed multi-way methodology
Simmel Studies
No full textArticles published in Simmel Studies are original articles, not yet published or considered for publication elsewhere. Contributors may submit articles in English, German and French, and each article should be accompanied by a brief abstract (150 words) in English and the complete address of the author, including e-mail.
Simmel Studies is abstracted and indexed by Sociological Abstracts (SA). Social Planning/Policy & Development Abstracts (SOPODA), and Linguistics and Language Behaviour Abstracts (LLBA)
Aurelio Mariani e il trittico dell'Assunta con i SS. Pietro e Paolo
No full textBreve analisi sul trittico dell'Assunta realizzato da Aurelio Mariani per la Cattedrale di Sor
Constantinopoli vista da P. Giulo Mancinelli S. J. (1583-1585)
No full textREB 60 2002 France p. 113-131
Vincenzo Ruggieri, Constantinopoli vista da P. Giulo Mancinelli S. J. (1583-1585). — The chief of the first Jesuit mission to Constantinople in the 1580's, P. Giulio Mancinelli, is the author of a report of the mission. Preserved in the General Archives of the Jesuit Order (Rome), this document also contains a contemporary description of Constantinople. The article presents an edition and commentary on this topographical part of Mancinelli' s report.La première mission jésuite à Constantinople, effectuée dans les années 1580, a eu pour chef P. Giulio Mancinelli, qui a laissé un rapport de cette mission. Conservé dans les Archives Générales de la Compagnie de Jésus (Rome), ce document comprend également une description contemporaine de Constantinople. C'est cette partie, topographique, qui est éditée et commentée dans l'article.Ruggieri Vincenzo. Constantinopoli vista da P. Giulo Mancinelli S. J. (1583-1585). In: Revue des études byzantines, tome 60, 2002. pp. 113-131
Car Sharing and Relocation Strategies: a Case Study Comparison in the Italian Market
No full textThe sharing economy represents an economic model based on the sharing of goods and services. In particular, this paper examines car sharing model, an attractive alternative to a self-owned car which has found large interest in the recent literature in different research fields. This study aims to investigate innovative and effective relocation strategies based on the analysis of data on users’ consumptions, for the constantly growing car sharing system. For this purpose, after a literature review, the paper presents a case study focused on the car repositioning algorithm developed by one of the market leader in this sector: car2go. More in detail, the paper evaluates differences and similarities in the strategic management of this model within the Italian context, through a comparison among the cities of Rome and Milan. Empirical results and practical implications for users will be provided, by highlighting opportunities and threats concerning the different settings
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