862 research outputs found

    «Fragmenta ne pereant». Sul ritrovamento di un nuovo testimone delle ‘Decretales’ di papa Gregorio IX

    No full text
    Sintesi e rielaborazione dei temi oggetto del precedente contributo - “Un nuovo frammento delle ‘Decretales’ di papa Gregorio IX, “AOFL. Università degli Studi di Ferrara. Annali online” 13 (2018), pp. 31-46 - incentrato sulla scoperta di un frammento delle ‘Decretales’ di Gregorio IX, tràdito da uno dei lacerti membranacei riutilizzati per rivestire la legatura di una cinquecentina contenente opere di Felino Sandeo, conservata nel Fondo antico della Biblioteca del Dipartimento di Giurisprudenza di Unife

    Un nuovo frammento delle ‘Decretales’ di papa Gregorio IX

    No full text
    Ricerca interdisciplinare su un antico stampa conservato presso la Biblioteca di Giurisprudenza dell'Univ. di Ferrara, mirata soprattutto allo studio dei frammenti pergamenacei utilizzati come rinforzo alla legatura di detto stampa. E' emerso così un nuovo testimone delle Decretali di papa Gregorio IX

    Meccanobiologia di sistemi biologici: da doppi strati lipidici a cellule in-vitro

    No full text
    Le proprietà meccaniche dei sistemi biologici hanno una grande importanza nel determinare il loro comportamento. Molti potenziali farmaci possono modificare le proprietà meccaniche della membrana biologica e indirettamente modulare la funzione di proteine di membrana. Analogamente, molti stati patologici a livello cellulare presentano un fenotipo con proprietà meccaniche alterate e la modifica di tali proprietà è tipicamente il risultato di una riorganizzazione del citoscheletro. Allo stesso tempo, le cellule sondano le proprietà reologiche della matrice extracellulare (ECM) attivando, a seconda della risposta ottenuta, diversi percorsi biochimici. Tali fenomeni sono spesso caratterizzati da una riorganizzazione citoscheletrica a seguito di stimoli periodici, come avviene ad esempio nel sistema cardiovascolare o nei polmoni. La scienza che tratta questi fenomeni è la meccanobiologia. Il lavoro di questa tesi di dottorato è dedicato all’analisi delle proprietà meccaniche di costituenti biologici, da semplici modelli di membrana, come doppi-strati-lipidici supportati (SLB) e vescicole giganti unilamellari (GUV), a sistemi quali colture cellulari in-vitro. Le tecniche di indagine usate hanno coinvolto: microscopia ottica in contrasto di fase, DIC e fluorescente; microscopia a forza atomica (AFM). Sono stati sviluppati, all’interno della tesi, metodi di analisi e dispositivi dedicati per specifiche applicazioni e misure di campioni. È stato progettato, testato e impiegato un incubatore per esperimenti di live-cell imaging da integrare direttamente sul tavolino (on-stage) di un microscopio ottico. Sono stati ottenuti simultaneamente parametri di migrazione di cellule esposte a diversi trattamenti, o poste su substrati aventi diversa rigidità meccanica. Lo stesso incubatore è stato ridisegnato per poter alloggiare uno stretcher uniassiale in grado di fornire al substrato specifiche funzioni periodiche di deformazione e valutare la conseguente risposta delle cellule in termini di migrazione e polarizzazione. Tra i metodi di indagine, è stata sviluppata l’analisi quantitativa di migrazione di singola cellula, ed è stato impiegato il modello “Persistence-Random-Walk”. Lo scopo era quello di analizzare l’effetto citostatico di un potenziale farmaco nelle cellule U87MG, usate come modello del glioblastoma multiforme. L’analisi effettuata ha infatti mostrato l’efficacia sia citostatica che antimitotica della molecola. Sono stati indagati inoltre i possibili meccanismi biochimici alla base di tali effetti. Nel contesto dei SLB e GUV è stata implementata rispettivamente l’analisi sulla tensione di linea di domini che simulano lipid-rafts e la costante di bending, basandosi sulla teoria delle fluttuazioni di membrana. Nel primo caso sono stati confrontati i risultati sulla misura della tensione di linea di miscele ternarie costituite da diverse componenti rilevanti nella formazione di lipid-rafts. Nel secondo caso, è stato valutato il ruolo di molecole esogene (peptidi antimicrobici e lipopeptidi) nella determinazione della costante di bending. Nella caratterizzazione visco-elastica del citoscheletro con AFM, è stato implementato un software basato sul modello di Ting, in grado di estrapolare i parametri viscoelastici dalle singole curve andata-ritorno. Si è studiato l’effetto del potenziale farmaco prima citato, sulle proprietà reologiche di cellule U87MG al fine di correlare migrazione e proprietà meccaniche cellulari. Sono stati sviluppati software dedicati alla ricerca di eventi Jump-Through-Force nell’analisi di SLB, e di eventi di estrazioni di tubi durante la retrazione della punta AFM sulla membrana plasmatica come possibile metodo per evidenziare variazioni di proprietà reologiche di membrane esposte a diversi trattamenti farmacologici.Mechanical properties of biological systems play a crucial role for their own behavior. As an example, many potential drugs could modify mechanical properties of the biological membrane and indirectly modulate transmembrane protein functions. Similarly, many pathological conditions at the cellular level are characterized by a phenotype with altered mechanical properties, and these alterations are due to cytoskeleton reorganization. At the same time, cells continuously probe rheological properties of extracellular matrix (ECM) enabling, depending on response obtained by the substrate, different downstream signaling cascades. In many cases, cytoskeleton reorganization occurs also when cells are experiencing periodic mechanical stimuli, as it happens for example in the cardiovascular system or in lungs. All these aspects are treated by a recent branch of physic and biology sciences: “Mechano-biology”. This PhD thesis work has been devoted to study some specific aspects of mechanical properties of biological systems: from simple models of the biological-membrane, like supported-lipid-bilayer (SLB) or giant-unilamellar-vescicle (GUV), to in-vitro cells. Investigation techniques exploited in this work include: phase-contrast optical microscopy, DIC and fluorescence microscopy and atomic force microscopy (AFM). In the thesis we developed analysis-methods and devices dedicated to specific application and measurements of biological samples. It has been designed, tested and employed successfully an on-stage cell incubator for live cell imaging. From time-lapse microscopy experiments we obtained different quantitative migration parameters both for cell exposed to different drugs and for cells seeded on substrates with different mechanical rigidity. The same cell incubator has been modified to include an uniaxial stretcher, able to provide specific periodic deformation functions to the substrate on which cells are growing, and we studied the effect of the periodic stimulation on cell migration and polarization. Among the different analysis methods, a single cell migration analysis protocol has been developed, exploiting the “Persistence-Random-Walk” model. The ultimate goal was that of analyzing the cytostatic effect of a potential drug for U87MG cell line, employed as model of the glioblastoma multiforme disease. The analysis has in fact shown the efficiency of this molecule for both migration and replication of this cell line. Furthermore, possible biochemical mechanisms of action involved in these effects have been investigated. In the context of SLBs and GUVs a line tension analysis of domains recapitulating lipid-raft and a bending constant measurement have been implemented, both based on Flickering spectroscopy theory. In the former case, line tension results of ternary mixture containing different components relevant for lipid-rafts formation have been compared for different lipid compositions. In the latter case, the role of exogenous molecules (antimicrobial peptides and lipopeptides) on the bending constant has been investigated. In viscoelastic characterization of the cell cytoskeleton through AFM, a Ting model-based software has been implemented, allowing to extrapolate viscoelastic parameters from single indentation-retraction curves. Using this method, the effect of the previously mentioned potential drug has been investigated, trying to correlate rheological properties to migration capabilities of U87MG. Finally, software dedicated to Jump-Through-Force curves by AFM to identify specific events on SLB, and tether pulling events during AFM tip retraction on plasma-membrane have been developed; in order to find possible methods to highlight variations in rheological properties of membrane exposed to different drug treatments

    Instantaneous Kinematics and Singularities of Two Types of Under-Actuated Parallel Wrists

    No full text
    S-(nS)PU-SPU and S-(nS)PU-2SPU are two out of three types of under-actuated wrists that are generated from the “ordinary” wrists of type S-3SPU (fully-parallel wrists), by replacing a spherical pair (S) with a nonholonomic spherical pair (nS) according to the rules stated in [1]. Position analysis, controllability, and path planning of these two wrist types have been addressed and solved in two previous papers [2, 3] of this author. Their kinetostatics and singularity analysis have not been addressed, yet; and they are studied in this paper. [1] Grosch, P., Di Gregorio, R., and Thomas, F., 2010, “Generation of under-actuated manipulators with nonholonomic joints from ordinary manipulators,” ASME J. of Mechanisms and Robotics, 2(1): 011005-(8 pages). [2] Di Gregorio R., 2011, “Under-Actuated Nonholonomic Parallel Wrists,” In: Proc. of the 13th World Congress in Mechanism and Machine Science (IFToMM 2011), Guanajuato, México, 19-25 June, 2011, Paper No. A12-264 [3] Di Gregorio, R., 2011, “On the S-(nS)PU-SPU and S-(nS)PU-2SPU under-actuated wrists,” Procs. of the ASME 2011 International Design Engineering Technical Conference & Computers and Information in Engineering Conference, IDETC/CIE 2011, August 28-31, 2011, Washington (DC, USA), Paper No.: DETC2011-47541

    Co-authorship network dataset on psoriasis research papers from Medline database (1942-2013).

    No full text
    A ".xlsx" file which provides data used by Gregorio González-Alcaide & collaborators in the article “Evolution of cooperation patterns in psoriasis research: co-authorship network analysis of papers in Medline (1942-2013).” The worksheet “labels” describes every variable. The worksheet “dataset” presents the following data: PMID: PubMed Identifier for indexed documents in Pubmed used for the study. PMIDs do not change over time or during processing and are never reused. DP: Date that the article was published. FAU: Author name for articles published. From 2002 forward, the full author name of authors is provided, if available. FAU-Revised: Author name after cleansing process. A standardization process of the variations in signatures from single authors was carried out. The main discrepancies we found were caused by one or more first or last names being included, the authors’ first names being either spelled out or abbreviated to the initials, and typos

    Co-authorship network dataset on psoriasis research papers from Medline database (1942-2013).

    No full text
    A ".xlsx" file which provides data used by Gregorio González-Alcaide & collaborators in the article “Evolution of cooperation patterns in psoriasis research: co-authorship network analysis of papers in Medline (1942-2013).” The worksheet “labels” describes every variable. The worksheet “dataset” presents the following data: PMID: PubMed Identifier for indexed documents in Pubmed used for the study. PMIDs do not change over time or during processing and are never reused. DP: Date that the article was published. FAU: Author name for articles published. From 2002 forward, the full author name of authors is provided, if available. FAU-Revised: Author name after cleansing process. A standardization process of the variations in signatures from single authors was carried out. The main discrepancies we found were caused by one or more first or last names being included, the authors’ first names being either spelled out or abbreviated to the initials, and typos

    Complex Phase Behavior of GUVs Containing Different Sphingomyelins

    No full text
    Understanding the lateral organization of biological membranes plays a key role on the road to fully appreciate the physiological functions of this fundamental barrier between the inside and outside regions of a cell. Ternary lipid bilayers composed of a high and a low melting temperature lipid and cholesterol represent a model system that mimics some of the important thermodynamical features of much more complex lipid mixtures such as those found in mammal membranes. The phase diagram of these ternary mixtures can be studied exploiting fluorescence microscopy in giant unilamellar vesicles, and it is typically expected to give rise, for specific combinations of composition and temperature, to regions of two-phase coexistence and a region with three-phase coexistence, namely, the liquid-ordered, liquid-disordered, and solid phases. Whereas the observation of two-phase coexistence is routinely possible using fluorescence microscopy, the three-phase region is more elusive to study. In this article, we show that particular lipid mixtures containing diphytanoyl-phosphatidylcholine and cholesterol plus different types of sphingomyelin (SM) are prone to produce bilayer regions with more than two levels of fluorescence intensity. We found that these intensity levels occur at low temperature and are linked to the copresence of long and asymmetric chains in SMs and diphytanoyl-phosphatidylcholine in the lipid mixtures. We discuss the possible interpretations for this observation in terms of bilayer phase organization in the presence of sphingolipids. Additionally, we also show that in some cases, liposomes in the three-phase coexistence state exhibit extreme sensitivity to lateral tension. We hypothesize that the appearance of the different phases is related to the asymmetric structure of SMs and to interdigitation effects

    Daptomycin Strongly Affects the Phase Behavior of Model Lipid Bilayers

    No full text
    Daptomycin (DAP) is a calcium-dependent cyclic lipopeptide with great affinity for negatively charged phospholipids bearing the phosphatidylglycerol (PG) headgroup and has been used since 2003 as a last resort antibiotic in the treatment of severe infections caused by Gram-positive bacteria. The first step of its mechanism of action involves the interaction with the bacterial membrane, which not only represents a physical barrier but also accommodates transmembrane proteins, such as receptors, transporters, and enzymes, whose activity is crucial for the survival of bacteria. This results in a less efficient development of resistance strategies by pathogens compared to common antibiotics that activate or inhibit biochemical pathways connected to specific target proteins. Although already on the market, the molecular mechanism of action of DAP is still a controversial subject of investigation and it is most likely the result of a combination of distinct effects. Understanding how DAP targets the membrane of pathogens could be of great help in finding its analogues that could better avoid the development of resistance. Here, exploiting fluorescence microscopy and atomic force microscopy (AFM), we demonstrated that DAP affects the thermodynamic behavior of lipid mixtures containing PG moieties. Regardless of whether the PG lipids are in the liquid or solid phase, DAP preferably interacts with this headgroup and is able to penetrate more deeply into the lipid bilayer in the regions where this headgroup is present. In particular, considering the results of an AFM/spectroscopy investigation, DAP appears to produce a stiffening effect of the domains where PG lipids are mainly in the fluid phase, whereas it causes fluidification of the domains where PG lipids are in the solid phase

    Scientometrics analysis of research activity and collaboration patterns in Chagas cardiomyopathy

    No full text
    An XLSX Excel file which provides data used by Gregorio González-Alcaide & collaborators in the article “Scientometrics analysis of research activity and collaboration patterns in Chagas cardiomyopathy” The worksheet “labels” describes the variables of the bibliographic databases that allow identifying the documents used to carry out the study. The worksheet “documents” present the following data: PMID: PubMed Identifier. TI: Title of journal article. AU: Author(s) of the document. SO: Source/journal title. PY: Publication year. MH: Medical Subject Headings (controlled vocabulary of biomedical terms) that is used to describe the subject of each journal article in MEDLINE. UT-WOS: Article Identifier in Web of Science (only present in articles indexed in Web of Science). TC: Times Cites in Web of Science Core Collection

    Scientometrics analysis of research activity and collaboration patterns in Chagas cardiomyopathy

    No full text
    An XLSX Excel file which provides data used by Gregorio González-Alcaide & collaborators in the article “Scientometrics analysis of research activity and collaboration patterns in Chagas cardiomyopathy” The worksheet “labels” describes the variables of the bibliographic databases that allow identifying the documents used to carry out the study. The worksheet “documents” present the following data: PMID: PubMed Identifier. TI: Title of journal article. AU: Author(s) of the document. SO: Source/journal title. PY: Publication year. MH: Medical Subject Headings (controlled vocabulary of biomedical terms) that is used to describe the subject of each journal article in MEDLINE. UT-WOS: Article Identifier in Web of Science (only present in articles indexed in Web of Science). TC: Times Cites in Web of Science Core Collection
    corecore