Mass-transport deposits on Mediterranean continental margins

Extensive mass transport deposits and multiple slide scars testify widespread and recurrent submarine sediment failures occurring during the late Quaternary on the SW-Adriatic and SE-Sicilian margins. These mass movements and their consequences contributed to shape the continental slopes and fill the basins with characteristic signatures. Geomorphological, seismo-stratigraphic, sedimentological and biostratigraphic data provide clues to: 1) define distinct failure mechanisms investigating on factors that determine dissimilar organization of coeval displaced masses, 2) reconstruct successive phases of failure stressing on the same location where slide scars crosscut and mass-transport deposits overlap, 3) analyze regional setting and indicate the most suitable place where to calculate mass wasting frequency. Discussions on the role of fluid flow, currents activity and tectonic deformation determine a wider view on the construction of the studied continental margins.

High-resolution stratigraphy of Central and Southern Adriatic Quaternary deposits of sub-Milankovian climate change on Mediterranean circulation

This volume is a collection of the work done in a three years-lasting PhD, focused in the analysis of Central and Southern Adriatic marine sediments, deriving from the collection of a borehole and many cores, achieved thanks to the good seismic-stratigraphic knowledge of the study area. The work was made out within European projects EC-EURODELTA (coordinated by Fabio Trincardi, ISMAR-CNR), EC-EUROSTRATAFORM (coordinated by Phil P. E. Weaver, NOC, UK), and PROMESS1 (coordinated by Serge Bernè, IFREMER, France). The analysed sedimentary successions presented highly expanded stratigraphic intervals, particularly for the last 400 kyr, 60 kyr and 6 kyr BP. These three different time-intervals resulted in a tri-partition of the PhD thesis. The study consisted of the analysis of planktic and benthic foraminifers’ assemblages (more than 560 samples analysed), as well as in preparing the material for oxygen and carbon stable isotope analyses, and interpreting and discussing the obtained dataset. The chronologic framework of the last 400 kyr was achieved for borehole PRAD1-2 (within the work-package WP6 of PROMESS1 project), collected in 186.5 m water depth. The proposed chronology derives from a multi-disciplinary approach, consisting of the integration of numerous and independent proxies, some of which analysed by other specialists within the project. The final framework based on: micropaleontology (calcareous nannofossils and foraminifers’ bioevents), climatic cyclicity (foraminifers’ assemblages), geochemistry (oxygen stable isotope, made out on planktic and benthic records), paleomagnetism, radiometric ages (14C AMS), teprhochronology, identification of sapropel-equivalent levels (Se). It’s worth to note the good consistency between the oxygen stable isotope curve obtained for borehole PRAD1-2 and other deeper Mediterranean records. The studied proxies allowed the recognition of all the isotopic intervals from MIS10 to MIS1 in PRAD1-2 record, and the base of the borehole has been ascribed to the early MIS11. Glacial and interglacial intervals identified in the Central Adriatic record have been analysed in detail for the paleo-environmental reconstruction, as well. For instance, glacial stages MIS6, MIS8 and MIS10 present peculiar foraminifers’ assemblages, composed by benthic species typical of polar regions and no longer living in the Central Adriatic nowadays. Moreover, a deepening trend in the paleo-bathymetry during glacial intervals was observed, from MIS10 (inner-shelf environment) to MIS4 (mid-shelf environment).Ten sapropel-equivalent levels have been recognised in PRAD1-2 Central Adriatic record. They showed different planktic foraminifers’ assemblages, which allowed the first distinction of events occurred during warm-climate (Se5, Se7), cold-climate (Se4, Se6 and Se8) and temperate-intermediate-climate (Se1, Se3, Se9, Se’, Se10) conditions, consistently with literature. Cold-climate sapropel equivalents are characterised by the absence of an oligotrophic phase, whereas warm-temeprate-climate sapropel equivalents present both the oligotrophic and the eutrophic phases (except for Se1). Sea floor conditions vary, according to benthic foraminifers’ assemblages, from relatively well oxygenated (Se1, Se3), to dysoxic (Se9, Se’, Se10), to highly dysoxic (Se4, Se6, Se8) to events during which benthic foraminifers are absent (Se5, Se7). These two latter levels are also characterised by the lamination of the sediment, feature never observed in literature in such shallow records. The enhanced stratification of the water column during the events Se8, Se7, Se6, Se5, Se4, and the concurring strong dilution of shallow water, pointed out by the isotope record, lead to the hypothesis of a period of intense precipitation in the Central Adriatic region, possibly due to a northward shift of the African Monsoon. Finally, the expression of Central Adriatic PRAD1-2 Se5 equivalent was compared with the same event, as registered in other Eastern Mediterranean areas. The sequence of substantially the same planktic foraminifers’ bioevents has been consistently recognised, indicating a similar evolution of the water column all over the Eastern Mediterranean; yet, the synchronism of these events cannot be demonstrated. A high resolution analysis of late Holocene (last 6000 years BP) climate change was carried out for the Adriatic area, through the recognition of planktic and benthic foraminifers’ bioevents. In particular, peaks of planktic Globigerinoides sacculifer (four during the last 5500 years BP in the most expanded core) have been interpreted, based on the ecological requirements of this species, as warm-climate, arid intervals, correspondent to periods of relative climatic optimum, such as, for instance, the Medieval Warm Period, the Roman Age, the Late Bronze Age and the Copper Age. Consequently, the minima in the abundance of this biomarker could correspond to relatively cooler and more rainy periods. These conclusions are in good agreement with the isotopic and the pollen data. The Last Occurrence (LO) of G. sacculifer has been dated in this work at an average age of 550 years BP, and it is the best bioevent approximating the base of the Little Ice Age in the Adriatic. Recent literature reports the same bioevent in the Levantine Basin, showing a rather consistent age. Therefore, the LO of G. sacculifer has the potential to be extended to all the Eastern Mediterranean. Within the Little Ice Age, benthic foraminifer V. complanata shows two distinct peaks in the shallower Adriatic cores analysed, collected hundred kilometres apart, inside the mud belt environment. Based on the ecological requirements of this species, these two peaks have been interpreted as the more intense (cold and rainy) oscillations inside the LIA. The chronologic framework of the analysed cores is robust, being based on several range-finding 14C AMS ages, on estimates of the secular variation of the magnetic field, on geochemical estimates of the activity depth of 210Pb short-lived radionuclide (for the core-top ages), and is in good agreement with tephrochronologic, pollen and foraminiferal data. The intra-holocenic climate oscillations find out in the Adriatic have been compared with those pointed out in literature from other records of the Northern Hemisphere, and the chronologic constraint seems quite good. Finally, the sedimentary successions analysed allowed the review and the update of the foraminifers’ ecobiostratigraphy available from literature for the Adriatic region, thanks to the achievement of 16 ecobiozones for the last 60 kyr BP. Some bioevents are restricted to the Central Adriatic (for instance the LO of benthic Hyalinea balthica , approximating the MIS3/MIS2 boundary), others occur all over the Adriatic basin (for instance the LO of planktic Globorotalia inflata during MIS3, individuating Dansgaard-Oeschger cycle 8 (Denekamp)).

Stratigraphy and Palaeontology of the Late Cretaceous Wapiti Formation, west-central Alberta, Canada

A complete stratigraphic assessment and revision of the middle Campanian to upper Maastrichtian Wapiti Formation in north-western Alberta and north-eastern British Columbia is the main aim of this research project. The study area encompasses an area of approximately 200X180 km in the Grande Prairie County (west-central Alberta) and easternmost British Columbia, Canada. Results presented here indicate that the 1300m thick succession currently reported in the literature as “undifferentiated lithostratigraphic unit”, consists of five lithostratigraphic units and four unconformity-bounded depositional sequences; their study and description have been documented integrating several geological disciplines, including sequence stratigraphic methods, well-log signatures, facies analysis, and fossil associations. On the whole, particular attention has been given to 1) age and nature of both basal and upper contacts of the Wapiti Formation, 2) effective mappability of lithostratigraphic units and depositional sequences in western Alberta, and 3) the identification of previously undetermined maximum flooding surface of the Bearpaw seaway and Drumheller Marine Tongue, which are reference marine unit in central and southern Alberta. A second, but not less important, guideline for the project has been the rich paleontological record of the Wapiti deposits. Detailed paleoenvironmental and taxonomical information on old and new finds have been the base for correlation with well known associations of Alaska, southern Alberta, and Montana. Newly discovered rich fossil localities documented an extraordinarily diverse fauna during the latest Cretaceous, including dinosaurs, squamates, and fresh-water fishes and reptiles. Lastly, in order to better characterize the Wapiti Formation, major marker beds were described: these include several bentonites (altered volcanic ash deposits) which have been documented over an area of almost 30.000 km2, as well as four major coal zones, characterized by tabular coal seams with an overall thickness of 2 meters. Such marker beds represent a formidable tool for high-resolution chronology and regional correlations within the Late Cretaceous Alberta foreland basin.

Stem cell pathways in the basal-like breast carcinoma: the role of beta-catenin and HIF-1alpha

Basal-like tumor is an aggressive breast carcinoma subtype that displays an expression signature similar to that of the basal/myoepithelial cells of the breast tissue. Basal-like carcinoma are characterized by over-expression of the Epidermal Growth Factor receptor (EGFR), high frequency of p53 mutations, cytoplasmic/nuclear localization of beta-catenin, overexpression of the Hypoxia inducible factor (HIF)-1alpha target Carbonic Anhydrase isoenzime 9 (CA9) and a gene expression pattern similar to that of normal and cancer stem cells, including the over-expression of the mammary stem cell markers CD44. In this study we investigated the role of p53, EGFR, beta-catenin and HIF-1alpha in the regulation of stem cell features and genes associated with the basal-like gene expression profile. The findings reported in this investigation indicate that p53 inactivation in ductal breast carcinoma cells leads to increased EGFR mRNA and protein levels. In our experimental model, EGFR overexpression induces beta-catenin cytoplasmatic stabilization and transcriptional activity and, by that, leads to increased aggressive features including mammosphere (MS) forming and growth capacity, invasive potential and overexpression of the mammary stem cell gene CD44. Moreover we found that EGFR/beta-catenin axis promotes hypoxia survival in breast carcinoma cells via increased CA9 expression. Indeed beta-catenin positively regulates CA9 expression upon hypoxia exposure. Interestingly we found that beta-catenin inhibits HIF-1alpha transcriptional activity. Looking for the mechanism, we found that CA9 expression is promoted by HIF-1alpha and cytoplasmatic beta-catenin further increased it post-transcriptionally, via direct mRNA binding and stabilization. These data reveal a functional beta-catenin/HIF-1alpha interplay among hallmarks of basal-like tumors and unveil a new functional role for cytoplasmic beta-catenin in the phenotype of such tumors. Therefore it can be proposed that the interplay here described among EGFR/beta-catenin and HIF-1alpha may play a role in breast cancer stem cell survival and function.

The stratigraphic record of the quaternary sea level fluctuations and the impact of the post-glacial sea level rise (Termination I) in the Adriatic basin (Mediterranean sea)

The modern stratigraphy of clastic continental margins is the result of the interaction between several geological processes acting on different time scales, among which sea level oscillations, sediment supply fluctuations and local tectonics are the main mechanisms. During the past three years my PhD was focused on understanding the impact of each of these process in the deposition of the central and northern Adriatic sedimentary successions, with the aim of reconstructing and quantifying the Late Quaternary eustatic fluctuations. In the last few decades, several Authors tried to quantify past eustatic fluctuations through the analysis of direct sea level indicators, among which drowned barrier-island deposits or coral reefs, or indirect methods, such as Oxygen isotope ratios (δ18O) or modeling simulations. Sea level curves, obtained from direct sea level indicators, record a composite signal, formed by the contribution of the global eustatic change and regional factors, as tectonic processes or glacial-isostatic rebound effects: the eustatic signal has to be obtained by removing the contribution of these other mechanisms. To obtain the most realistic sea level reconstructions it is important to quantify the tectonic regime of the central Adriatic margin. This result has been achieved integrating a numerical approach with the analysis of high-resolution seismic profiles. In detail, the subsidence trend obtained from the geohistory analysis and the backstripping of the borehole PRAD1.2 (the borehole PRAD1.2 is a 71 m continuous borehole drilled in -185 m of water depth, south of the Mid Adriatic Deep - MAD - during the European Project PROMESS 1, Profile Across Mediterranean Sedimentary Systems, Part 1), has been confirmed by the analysis of lowstand paleoshorelines and by benthic foraminifera associations investigated through the borehole. This work showed an evolution from inner-shelf environment, during Marine Isotopic Stage (MIS) 10, to upper-slope conditions, during MIS 2. Once the tectonic regime of the central Adriatic margin has been constrained, it is possible to investigate the impact of sea level and sediment supply fluctuations on the deposition of the Late Pleistocene-Holocene transgressive deposits. The Adriatic transgressive record (TST - Transgressive Systems Tract) is formed by three correlative sedimentary bodies, deposited in less then 14 kyr since the Last Glacial Maximum (LGM); in particular: along the central Adriatic shelf and in the adjacent slope basin the TST is formed by marine units, while along the northern Adriatic shelf the TST is represented by costal deposits in a backstepping configuration. The central Adriatic margin, characterized by a thick transgressive sedimentary succession, is the ideal site to investigate the impact of late Pleistocene climatic and eustatic fluctuations, among which Meltwater Pulses 1A and 1B and the Younger Dryas cold event. The central Adriatic TST is formed by a tripartite deposit bounded by two regional unconformities. In particular, the middle TST unit includes two prograding wedges, deposited in the interval between the two Meltwater Pulse events, as highlighted by several 14C age estimates, and likely recorded the Younger Dryas cold interval. Modeling simulations, obtained with the two coupled models HydroTrend 3.0 and 2D-Sedflux 1.0C (developed by the Community Surface Dynamics Modeling System - CSDMS), integrated by the analysis of high resolution seismic profiles and core samples, indicate that: 1 - the prograding middle TST unit, deposited during the Younger Dryas, was formed as a consequence of an increase in sediment flux, likely connected to a decline in vegetation cover in the catchment area due to the establishment of sub glacial arid conditions; 2 - the two-stage prograding geometry was the consequence of a sea level still-stand (or possibly a fall) during the Younger Dryas event. The northern Adriatic margin, characterized by a broad and gentle shelf (350 km wide with a low angle plunge of 0.02° to the SE), is the ideal site to quantify the timing of each steps of the post LGM sea level rise. The modern shelf is characterized by sandy deposits of barrier-island systems in a backstepping configuration, showing younger ages at progressively shallower depths, which recorded the step-wise nature of the last sea level rise. The age-depth model, obtained by dated samples of basal peat layers, is in good agreement with previous published sea level curves, and highlights the post-glacial eustatic trend. The interval corresponding to the Younger Dyas cold reversal, instead, is more complex: two coeval coastal deposits characterize the northern Adriatic shelf at very different water depths. Several explanations and different models can be attempted to explain this conundrum, but the problem remains still unsolved.

Generation and characterization of mouse models of Small cell lung cancer and Basal cell carcinoma for the preclinical evaluation of new therapies

Background. Human small cell lung cancer (SCLC) accounting for approximately 15-20% of all lung cancers, is an aggressive tumor with high propensity for early regional and distant metastases. Although the initial tumor rate response to chemotherapy is very high, SCLC relapses after approximately 4 months in ED and 12 months in LD. Basal cell carcinoma (BCC) is the most prevalent cancer in the western world, and its incidence is increasing worldwide. This type of cancer rarely metastasizes and the death rate is extraordinary low. Surgery is curative for most of the patients, but for those that develop locally advanced or metastatic BCC there is currently no effective treatment. Both types of cancer have been deeply investigated and genetic alterations, MYCN amplification (MA) among the most interesting, have been found. These could become targets of new pharmacological therapies. Procedures. We created and characterized novel BLI xenograft orthotopic mouse models of SCLC to evaluate the tumor onset and progression and the efficacy of new pharmacological strategies. We compared an in vitro model with a transgenic mouse model of BCC, to investigate and delineate the canonical HH signalling pathway and its connections with other molecular pathways. Results and conclusions. The orthotopic models showed latency and progression patterns similar to human disease. Chemotherapy treatments improved survival rates and validated the in vivo model. The presence of MA and overexpression were confirmed in each model and we tested the efficacy of a new MYCN inhibitor in vitro. Preliminar data of BCC models highlighted Hedgehog pathway role and underlined the importance of both in vitro and in vivo strategies to achieve a better understanding of the pathology and to evaluate the applicability of new therapeutic compounds

Airway Basal Cell Vascular Endothelial Growth Factor-mediated Cross-Talk Regulates Endothelial Cell Dependent Growth Support of Human Airway Basal Cells

The human airway epithelium is a pseudostratified heterogenous layer comprised of cili-ated, secretory, intermediate and basal cells. As the stem/progenitor population of the airway epi-thelium, airway basal cells differentiate into ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. Transcriptome analysis of airway basal cells revealed high expression of vascular endothelial growth factor A (VEGFA), a gene not typically associated with the function of this cell type. Using cultures of primary human airway basal cells, we demonstrate that basal cells express all of the 3 major isoforms of VEGFA (121, 165 and 189) but lack functional expression of the classical VEGFA receptors VEGFR1 and VEGFR2. The VEGFA is actively secreted by basal cells and while it appears to have no direct autocrine function on basal cell growth and proliferation, it functions in a paracrine manner to activate MAPK signaling cascades in endothelium via VEGFR2 dependent signaling pathways. Using a cytokine- and serum-free co-culture system of primary human airway basal cells and human endothelial cells revealed that basal cell secreted VEGFA activated endothelium to ex-press mediators that, in turn, stimulate and support basal cell proliferation and growth. These data demonstrate novel VEGFA mediated cross-talk between airway basal cells and endothe-lium, the purpose of which is to modulate endothelial activation and in turn stimulate and sustain basal cell growth.

Paleosol-based stratigraphy of late Quaternary deposits from the Po basin, between Bologna and the Po river (Northern Italy)

Stratigraphic studies carried out over the last decades in Italy and elsewhere testify a growing interest in Quaternary deposits and in the influence of climate change on their architecture. The subsurface of the Po Plain, in its topmost portion, is made up of alluvial deposits organized in depositional cycles at different scales. This PhD thesis provides millennial-scale stratigraphic reconstruction of the Late Pleistocene-Holocene deposits beneath the southern Po Plain, based on basin-scale correlation of laterally-extensive buried soil horizons. Far from the aim of characterizing palaeosols from a mineralogical and geochemical point of view, we focused on the physical and stratigraphic significance of these horizons. In the Bologna urban area, which hosts an abundance of stratigraphic data, the correlation between seventeen continuously-cored boreholes led to the identification of five vertically-stacked palaeosol-bounded sequences within the 14C time window. In a wide portion of the alluvial plain north of Bologna, far away from the Apenninic margin and from the Po River, where subsurface stratigraphic architecture is dominated by markedly lenticular sediment bodies, palaeosols revealed to be the only stratigraphic marker of remarkable lateral continuity. These horizons are characterized by peculiar resistance values, which make them easily identifiable via pocket penetration tests. Palaeosols reveal specific geometric relationships with the associated alluvial facies associations, allowing reliable estimates of soil development as a function of alluvial dynamics. With the aid of sixty new radiocarbon dates, a reliable age attribution and likely time intervals of exposure were assigned to each palaeosol. Vertically-stacked palaeosols delimitate short-term depositional cycles, likely related to the major episodes of climatic change of the last 40 ky. Through integration of stratigraphic data with 750 archaeological reports from the Bologna area, the impact of human settlements on depositional and pedogenic processes during the late Holocene was investigated.