Interannual analysis of high spatially-resolved δ18O and δ2H data in precipitation across North-East Italy

Stable water isotopes are widely-used tracers to investigate hydrological processes occurring in the atmosphere and to determine the geospatial origin of water, i.e. to acquire useful information about the hydrological cycles over catchment basins and to find the origin of water recharging rivers, aquifers, and springs. Mapping the isotopic composition of precipitation provides hydrological and climate information at regional and global scales. However, the isotopic composition of precipitation is usually analyzed at large scales with a limited spatial resolution. In Italy, a few studies mapped the oxygen stable isotopes using annually-averaged data, not accounting for the strong seasonality of the isotopic composition linked to climatic and weather factors. To partially fill this gap, the present study proposes a detailed analysis of more than 2250 isotope data (δ18O, δ2H, and deuterium excess) related to precipitations collected in the Friuli Venezia Giulia (FVG) region (Italy) with monthly or seasonal frequency in 36 sites between 1984 and 2015. The FVG region lies at the north-eastern end of Italy, bordering Austria in the North and Slovenia in the East, and extends over ~7.9·103 km2. From a hydrogeological point of view, FVG is an interesting case study. Large highly-permeable carbonate aquifers are present in the Alps and Prealps, while the southern part of the region is characterized by an alluvial plain, split by the spring belt into two sectors: the High Plain in the North, characterized by an highly-permeable unconfined aquifer, and the Low Plain in the South, characterized by a system of confined and artesian aquifers. All the aquifers are recharged by the effective precipitations which in the FVG exhibits among the highest annual precipitation rates in Italy (with peaks >3000 mm/year). For the present research, the isotopic data were used: (i) to analyze the spatial and seasonal variability of isotopic composition; (ii) to relate water isotopes with orography and weather parameters collected from meteorological stations as well as using ECMWF ERA5 reanalysis; (iii) to reconstruct the local meteoric water lines across the FVG at annual and seasonal bases; (iv) to quantify interannual trends and analyze their spatial distribution; and (iv) to model the spatial distribution of isotope content in precipitation and create annual and seasonal maps

Three-year monitoring of stable isotopes of precipitation at Concordia Station, East Antarctica

Past temperature reconstructions from Antarctic ice cores require a good quantification and understanding of the relationship between snow isotopic composition and 2m air or inversion (condensation) temperature. Here, we focus on the French-Italian Concordia Station, central East Antarctic plateau, where the European Project for Ice Coring in Antarctica (EPICA) Dome C ice cores were drilled. We provide a multi-year record of daily precipitation types identified from crystal morphologies, daily precipitation amounts and isotopic composition. Our sampling period (2008-2010) encompasses a warmer year (2009, +1.2 degrees C with respect to 2m air temperature long-term average 1996-2010), with larger total precipitation and snowfall amounts (14 and 76% above sampling period average, respectively), and a colder and drier year (2010, -1.8 degrees C, 4% below long-term and sampling period averages, respectively) with larger diamond dust amounts (49% above sampling period average). Relationships between local meteorological data and precipitation isotopic composition are investigated at daily, monthly and inter-annual scale, and for the different types of precipitation. Water stable isotopes are more closely related to 2m air temperature than to inversion temperature at all timescales (e.g. R-2 = 03 and 0.44, respectively for daily values). The slope of the temporal relationship between daily delta O-18 and 2m air temperature is approximately 2 times smaller (0.49 parts per thousand degrees C-1) than the average Antarctic spatial (0.8 parts per thousand degrees C-1) relationship initially used for the interpretation of EPICA Dome C records. In accordance with results from precipitation monitoring at Vostok and Dome F, deuterium excess is anticorrelated with delta O-18 at daily and monthly scales, reaching maximum values in winter. Hoar frost precipitation samples have a specific fingerprint with more depleted delta O-18 (about 5% below average) and higher deuterium excess (about 8% above average) values than other precipitation types. These datasets provide a basis for comparison with shallow ice core records, to investigate post-deposition effects. A preliminary comparison between observations and precipitation from the European Centre for Medium-RangeWeather Forecasts (ECMWF) reanalysis and the simulated water stable isotopes from the Laboratoire de Meteorologie Dynamique Zoom atmospheric general circulation model (LMDZiso) shows that models do correctly capture the amount of precipitation as well as more than 50% of the variance of the observed delta O-18, driven by large-scale weather patterns. Despite a warm bias and an underestimation of the variance in water stable isotopes, LMDZiso correctly captures these relationships between delta O-18, 2m air temperature and deuterium excess. Our dataset is therefore available for further in-depth model evaluation at the synoptic scale

Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer

Osteopontin (OPN), also known as SPP1 (secreted phosphoprotein), is an integrin binding glyco-phosphoprotein produced by a variety of tissues. In cancer patients expression of OPN has been associated with poor prognosis in several tumor types including breast, lung, and colorectal cancers. Despite wide expression in tumor cells and stroma, there is limited evidence supporting role of OPN in tumor progression and metastasis. Using phage display technology we identified a high affinity anti-OPN monoclonal antibody (hereafter AOM1). The binding site for AOM1 was identified as SVVYGLRSKS sequence which is immediately adjacent to the RGD motif and also spans the thrombin cleavage site of the human OPN. AOM1 efficiently inhibited OPNa binding to recombinant integrin αvβ3 with an IC50 of 65 nM. Due to its unique binding site, AOM1 is capable of inhibiting OPN cleavage by thrombin which has been shown to produce an OPN fragment that is biologically more active than the full length OPN. Screening of human cell lines identified tumor cells with increased expression of OPN receptors (αvβ3 and CD44v6) such as mesothelioma, hepatocellular carcinoma, breast, and non-small cell lung adenocarcinoma (NSCLC). CD44v6 and αvβ3 were also found to be highly enriched in the monocyte, but not lymphocyte, subset of human peripheral blood mononuclear cells (hPBMCs). In vitro, OPNa induced migration of both tumor and hPBMCs in a transwell migration assay. AOM1 significantly blocked cell migration further validating its specificity for the ligand. OPN was found to be enriched in mouse plasma in a number of pre-clinical tumor model of non-small cell lung cancers. To assess the role of OPN in tumor growth and metastasis and to evaluate a potential therapeutic indication for AOM1, we employed a KrasG12D-LSLp53fl/fl subcutaneously implanted in vivo model of NSCLC which possesses a high capacity to metastasize into the lung. Our data indicated that treatment of tumor bearing mice with AOM1 as a single agent or in combination with Carboplatin significantly inhibited growth of large metastatic tumors in the lung further supporting a role for OPN in tumor metastasis and progression

Spatial distribution and interannual trends of \u3b418O, \u3b42H, and deuterium excess in precipitation across North-Eastern Italy

NE Italy presents high-quantity, high-quality and easily exploitable groundwater resources that are seriously threatened by anthropogenic pressures. This study analyzes the oxygen and hydrogen isotopic composition of 2250 precipitation samples collected in 36 sites across the north-easternmost region of Italy, Friuli Venezia Giulia, between 1984 and 2015. This is an unprecedented dataset for North Italy with a high density of sampling sites and a decadal temporal extension. A series of both routine and original chemometric approaches were applied to investigate the temporal and spatial variability of the isotopic composition through relationships with geographical and weather variables. New statistical approaches were presented to model the seasonal and spatial patterns of isotopic composition as well as to summarize the large amount of isotopic data. Significant gradients of \u3b418O and \u3b42H were detected in the area due to the peculiar orography and climate of the region; the amplitude of the monthly patterns also presented similar gradients. The deuterium excess did not present a clear seasonality, but higher values were found in autumn. The deuterium excess-to-\u3b418O ratio exhibited typical patterns throughout the region when grouping the sites for altitude and continentality; in winter, large differences of \u3b418O were detected among groups, but deuterium excess remained almost unchanged. The inter-site correlations were moderately high across all the territory even for deseasonalized data. The local meteoric water line (using all the single samples \u3b42H=7.8\ub7\u3b418O+8.9) was also estimated at annual and seasonal basis, evidencing the presence of spatial gradients according to the orographic and weather characteristics of the region. Statistically significant increasing interannual trends (0.23\u20130.87\u2030/y) were detected in 11 sites for deuterium excess; the presence of these trends was linked to local processes. Two multiple linear regression models were applied to reconstruct the isotopic composition of precipitation at a regional scale. The stepwise approach returned the best results with root mean square errors in the 0.5-1\u2030, 3.5\u20138.2\u2030 and 0.9\u20131.5\u2030 intervals for \u3b418O, \u3b42H, and deuterium excess, respectively. The deuterium excess was not modelled in winter, where no relationships were found with geographic variables

Spatial distribution and interannual trends of δ18O, δ2H, and deuterium excess in precipitation across North-Eastern Italy

NE Italy presents high-quantity, high-quality and easily exploitable groundwater resources that are seriously threatened by anthropogenic pressures. This study analyzes the oxygen and hydrogen isotopic composition of 2250 precipitation samples collected in 36 sites across the north-easternmost region of Italy, Friuli Venezia Giulia, between 1984 and 2015. This is an unprecedented dataset for North Italy with a high density of sampling sites and a decadal temporal extension. A series of both routine and original chemometric approaches were applied to investigate the temporal and spatial variability of the isotopic composition through relationships with geographical and weather variables. New statistical approaches were presented to model the seasonal and spatial patterns of isotopic composition as well as to summarize the large amount of isotopic data. Significant gradients of δ18O and δ2H were detected in the area due to the peculiar orography and climate of the region; the amplitude of the monthly patterns also presented similar gradients. The deuterium excess did not present a clear seasonality, but higher values were found in autumn. The deuterium excess-to-δ18O ratio exhibited typical patterns throughout the region when grouping the sites for altitude and continentality; in winter, large differences of δ18O were detected among groups, but deuterium excess remained almost unchanged. The inter-site correlations were moderately high across all the territory even for deseasonalized data. The local meteoric water line (using all the single samples ) was also estimated at annual and seasonal basis, evidencing the presence of spatial gradients according to the orographic and weather characteristics of the region. Statistically significant increasing interannual trends (0.23-0.87 ‰/y) were detected in 11 sites for deuterium excess; the presence of these trends was linked to local processes. Two multiple linear regression models were applied to reconstruct the isotopic composition of precipitation at a regional scale. The stepwise approach returned the best results with root mean square errors in the 0.5-1‰, 3.5-8.2‰ and 0.9-1.5‰ intervals for δ18O, δ2H, and deuterium excess, respectively. The deuterium excess was not modelled in winter, where no relationships were found with geographic variables