Alterazioni dell'immunità umorale nei pazienti con sarcoma di Kaposi classico: caratterizzazione dei linfociti B circolanti e delle loro sottopopolazioni

Objectives: Human Herpesvirus 8 (HHV-8) is the etiological agent of Kaposi’s Sarcoma (KS) and it is also associated with two B cell lymphoproliferative diseases: primary effusion lymphoma (PEL), and the plasmablastic form of multicentric Castelman’s disease (MCD). HHV-8 establishes persistent infection in the host with tropism for multiple cell types. In KS patients, the virus is found in tumor-spindle cells, peripheral blood monocytes, endothelial progenitor circulating cells, T and B lymphocytes. Peripheral B cells represent one of the major virus reservoir, but the consequences of HHV-8 infection of these cells have been poorly characterized. Therefore, in this study the frequency, the immunophenotypic profile and the functional activity of different peripheral B cell subsets in patients with classic KS (cKS) was analysed in order to identify potential alterations of these cells. The classic variant of KS is ideal to perform such studies, as it lacks confounding factors such as HIV or EBV infection and immunosuppression. Methods: Whole-blood samples from patients with the classical form of KS (cKS) (n=62) and healthy age and sex-matched seronegative controls (HSN) (n=43) were analyzed by multiparametric flow-cytometry to determine the frequency of B cells and their subpopulations, as well as their surface expression of immunoglobulins and activation markers. Results: The frequency of circulating B cells was significantly higher in cKS patients than in controls. In particular, the analysis of the B cell subsets revealed a higher frequency of naïve B cells (CD19+CD27-), among which transitional CD19+CD38highCD5+ and pre-naïve (CD27-CD38intCD5+ ) B cells demonstrated an expansion. Memory B cells (CD19+CD27+) did not differ between the two study groups, except from a higher frequency of CD19+CD27+IgM+IgD+ B cells, the typical phenotype of marginal zone (MZ) B cells, in cKS patients. The characterization of membrane surface activation markers showed lower levels of the activation marker HLA-DR only on CD27- B cells, while CD80 and CD86 were less represented in all the the B cells from cKS patients. Moreover, B cells from cKS patients were smaller and with less granules than the ones from controls. Conclusion: Taken together, these results clearly indicate that circulating B cells are altered in patients with cKS, showing an expansion of the immature phenotypes. These B cell alterations may be due to an indirect viral effect rather than to a direct one: the cytokines expressed in the microenvironment typical of cKS may cause a faster release of immature cells from the bone marrow and a lower grade of peripheral differentiation, as already suggested for other chronic viral infections such as HIV and HCV. Further studies will be necessary to understand how these alterations contribute to the pathogenesis of KS and, eventually, to the different clinical evolution of the disease.

Zum Transport von partikelgebundenen Schadstoffen in der ungesättigten Zone

Bei einer Risikoabschätzung bezüglich einer Gefährdung des Schutzgutes Grundwasser müssen alle relevanten Transportpfade, auf denen Schadstoffe durch die Bodenzone bis ins Grundwasser verlagert werden, identifiziert und quantifiziert werden. Die Verlagerung von Schadstoffen gebunden an mobile Partikel im Sickerwasser wird dabei oft vernachlässigt. In dieser Arbeit wurden sowohl experimentelle Untersuchungen zum Partikeltransport in der Bodenzone als auch Szenarienmodellierungen hinsichtlich der Wechselwirkung Partikel/Schadstoff durchgeführt. Die experimentellen ungesättigten Säulenversuche wurden unter naturnahen stationären und instationären hydraulischen und hydrochemischen Bedingungen durchgeführt. Dabei wurde der Einfluss der Parameter Durchmesser Bodenmatrix, Partikelgröße, Beregnungsintensität, Oberflächenspannung und Hydrochemie auf den Transport von natürlichen und synthetischen Partikeln untersucht. Des Weiteren wurden Untersuchungen zur partikelgebundenen Verlagerung von Phenanthren durchgeführt. In einer numerischen Szenarienmodellierung mit dem Modell SMART wurde untersucht, unter welchen Randbedingungen der Transport von Partikeln gleichzeitig zu signifikanten partikelgebundenen Schadstoffkonzentrationen im Grundwasser führt. Dabei wurden die Parameter Lithologie Partikel/Boden, Hydrophobizität Schadstoff, Partikelkonzentration, Partikeldurchmesser sowie Körnung Bodenmatrix variiert. Die Ergebnisse dieser Arbeit zeigen, dass der partikelgebundene Schadstofftransportpfad in der ungesättigten Bodenzone in verschiedenen Szenarien den Anteil mobiler Schadstoffe, die mit dem Sickerwasser ins Grundwasser gelangen, signifikant erhöht. Auf Basis der experimentellen und theoretischen Untersuchungen wurde ein zweistufiges Bewertungsschema entwickelt, das bereits im Vorfeld einer Risikoabschätzung als Entscheidungshilfe hinsichtlich der Relevanz einer Mobilisierung, eines Transports und des Rückhalts von partikelgebundenen Schadstoffen in der ungesättigten Zone dient.

Climate impact studies of sediment transport on the Adriatic coastal zone

The study of the impact of climate change on the environment has been based, until very recently, on an global approach, whose interest from a local point of view is very limited. This thesis, on the contrary, has treated the study of the impact of climate change in the Adriatic Sea basin following a twofold strategy of regionalization and integration of numerical models in order to reproduce the present and future scenarios of the system through a more and more realistic and solid approach. In particular the focus of the study was on the impact on the physical environment and on the sediment transport in the basin. This latter is a very new and original issue, to our knowledge still uninvestigated. The study case of the coastal area of Montenegro was particularly studied, since it is characterized by an important supply of sediment through the Buna/Bojana river, second most important in the Adriatic basin in terms of flow. To do this, a methodology to introduce the tidal processes in a baroclinic primitive equations Ocean General Circulation Model was applied and tidal processes were successfully reproduced in the Adriatic Sea, analyzing also the impacts they have on the mean general circulation, on salt and heat transport and on mixing and stratification of the water column in the different seasons of the year. The new hydrodynamical model has been further coupled with a wave model and with a river and sea sediment transport model, showing good results in the reproduction of sediment transport processes. Finally this complex coupled platform was integrated in the period 2001-2030 under the A1B scenario of IPCC, and the impact of climate change on the physical system and on sediment transport was preliminarily evaluated.

The pre-alpine evolution of the basement of the Pelagonian Zone and the Vardar Zone, Greece

The Pelagonian Zone and the Vardar Zone in Greece represent the western part of the Hellenide hinterland (Internal Hellenides). While the Pelagonian Zone comprises predominantly crystalline basement and sedimentary cover rocks, the Vardar Zone has long been regarded as an ophiolite-decorated suture zone separating the Pelagonian Zone from the Serbo-Macedonian Massif to the east. Felsic basement rocks from both areas, with the main focus put on the Pelagonian Zone, were dated in order to identify the major crust-forming episodes and to improve the understanding of the evolutionary history of the region. The interpretation of the single-zircon geochronology results was aided by geochemical investigations. The majority of the basement rocks from the Pelagonian Zone yielded Permo-Carboniferous intrusion ages around 300 Ma, underlining the importance of this crust-forming event for the Internal Hellenides of Greece. Geochemically these basement rocks are classified as subduction-related granitoids, which formed in an active continental margin setting. An important result was the identification of a Precambrian crustal unit within the crystalline basement of the Pelagonian Zone. Orthogneisses from the NW Pelagonian Zone yielded Neoproterozoic ages of c. 700 Ma and are so far the oldest known rocks in Greece. These basement rocks, which are also similar to active margin granitoids, were interpreted as remnants of a terrane, the Florina Terrane, which can be correlated to a Pan-African or Cadomian arc. Since the gneisses contain inherited zircons of Middle to Late Proterozoic ages, the original location of the Florina Terrane was probably at the northwestern margin of Gondwana. In the Vardar Zone an important phase of Upper Jurassic felsic magmatism is documented by igneous formation ages ranging from 155 to 164 Ma. The chemical and isotopic composition of these rocks is also in accord with their formation in a volcanic-arc setting at an active continental margin. Older continental material incorporated in the Vardar Zone is documented by 319-Ma-old gneisses and by inherited zircons of mainly Middle Palaeozoic ages. The prevalence of subduction-related igneous rocks indicates that arc formation and accretion orogeny were the most important processes during the evolution of this part of the Internal Hellenides. The geochronological results demonstrate that most of the Pelagonian Zone and the Vardar Zone crystalline basement formed during distinct pre-Alpine episodes at c. 700, 300 and 160 Ma with a predominance of the Permo-Carboniferous magmatic phase.

Relazione fra comunità macrobentoniche e morfodinamica nelle zone costiere dell’Alto Adriatico

Numerosi studi hanno messo in evidenza che la struttura delle comunità macrobentoniche delle spiagge sabbiose dipende da una serie di forzanti fisiche; queste ultime interagendo tra loro determinano la morfodinamica della spiagge stesse. Lo scopo di questo lavoro consiste nell’analisi dei popolamenti macrobentonici di due siti presenti lungo la costa emiliano - romagnola, che differiscono per caratteristiche morfodinamiche, grado di antropizzazione e modalità gestionali di difesa dall’erosione costiera. I siti oggetto di studio sono Lido Spina e Bellocchio; il primo è soggetto ad interventi di ripascimento periodici, mentre il secondo rappresenta un’opportunità rara, per lo studio degli effetti del retreat, in quanto è in forte erosione da molti anni ma, essendo inserito all’interno di una riserva naturale, non è sottoposto ad alcuna misura di gestione. Sono state analizzate le comunità macrobentoniche e le variabili abiotiche (mediana e classazione del sedimento, ampiezza della zona intertidale, pendenza della spiaggia, contenuto di sostanza organica totale presente nel sedimento e i principali parametri chimico-fisici). I risultati del presente studio hanno evidenziato un’elevata eterogeneità della struttura di comunità all’interno del sito di Bellocchio rispetto a Spina; inoltre i popolamenti presenti a Bellocchio mostrano una netta differenza tra i due livelli mareali. Per quanto riguarda i descrittori abiotici, i due siti differiscono per ampiezza della zona intertidale e pendenza della spiaggia; in particolare Lido Spina presenta una condizione di minore dissipatività, essendo caratterizzata da un profilo più ripido e una granulometria più grossolana rispetto a Bellocchio. Nel complesso le caratteristiche granulometriche (mediana e classazione) e il contenuto di materia organica rappresentano le variabili ambientali maggiormente responsabili delle differenze osservate tra i popolamenti macrobentonici analizzati. Al fine di valutare la resistenza dell’habitat intertidale agli eventi naturali di disturbo (storm surge e flooding), sono state effettuare delle simulazioni considerando lo scenario attuale (SLR=0), mediante un modello ibrido fuzzy naive Bayes. I risultati indicano una maggiore resistenza delle comunità presenti nel sito di Spina, in quanto non si hanno variazioni significative del numero medio di taxa e di individui; viceversa le simulazioni relative a Bellocchio mostrano una diminuzione del numero medio di taxa e aumento del numero medio di individui, sottolineando una maggiore vulnerabilità delle comunità macrobentoniche presenti in questo sito. L’inasprimento dei fenomeni estremi potrebbe quindi avere un effetto negativo sulla diversità della componente macrobentonica, soprattutto per gli ambienti di transizione già interessati da fenomeni erosivi, come nel caso di Bellocchio. La perdita di specie, che svolgono processi ecosistemici particolarmente importanti, come il riciclo di nutrienti, potrebbe favorire l’aumento di abbondanza di specie opportunistiche, l’insediamento di specie alloctone, con la conseguente alterazione, se non scomparsa delle principali funzioni ecologiche svolte da questi ecosistemi costieri.

Ophiolites of the eastern Vardar Zone, N. Greece

In the present thesis, the geochemistry, petrology and geochronology of ophiolite complexes from central northern Greece were studied in detail in order to gain insights on the petrogenetic pathways and geodynamic processes that lead to their formation and evolution. The major- and trace-element content of minerals and whole rocks from all four ophiolite complexes was determined using high-precision analytical equipment. These results were then coupled with Nd and Sr isotopic measurements. In order to precisely place the evolution of these ophiolites in time, U-Pb geochronology on zircons was conducted using a SHRIMP-II. The data obtained suggest that the ophiolites studied invariably show typical characteristics of subduction-zone magmatism (e.g. negative Nb anomalies, Th enrichment). In N-MORB-normalised multielement profiles the high field-strength elements display patterns that vary from depleted to N-MORB-like. Chondrite-normalised rare-earth element (REE) profiles show flat heavy-REE patterns suggesting a shallow regime of source melting for all the ophiolites, well within the stability field of spinel lherzolite. The majority of the samples have light-REE depleted patterns. 87Sr/86Sr isotopic ratios range from 0.703184 to 0.715853 and are in cases influenced by alteration. The εNd values are positive (the majority of the mafic samples is typically 7.1-3.1) but lower than N-MORB and depleted mantle. With the exception of the Thessaloniki ophiolite that has uniform island-arc tholeiitic chemical characteristics, the rest of the ophiolites show dual chemistry consisting of rocks with minor subduction-zone characteristics that resemble chemically back-arc basin basalts (BABB) and rocks with more pronounced subduction-zone characteristics. Tectonomagmatic discrimination schemes classify the samples as island-arc tholeiites and back-arc basin basalts or N-MORB. Melting modelling carried out to evaluate source properties and degree of melting verifies the dual nature of the ophiolites. The samples that resemble back-arc basin basalts require very small degrees of melting (<10%) of fertile sources, whereas the rest of the samples require higher degrees (25-15%) of melting. As deduced from the present geochemical and petrological investigation, the ophiolites from Guevguely, Oraeokastro, Thessaloniki, and Chalkidiki represent relics of supra-subduction zone crust that formed in succeeding stages of island-arc rifting and back-arc spreading as well as in a fore arc setting. The geochronological results have provided precise determination of the timing of formation of these complexes. The age of the Guevguely ophiolite has been determined as 167±1.2 Ma, that of Thessaloniki as 169±1.4 Ma, that of Kassandra as 167±2.2 Ma and that of Sithonia as 160±1.2 Ma.