618 research outputs found
Relationship between rainfall and flood frequency curves in high elevation areas
Flood hazard assessment and its relationship with extreme rainfall probabilities is a welladdressed
topic in the literature, but not enough in mountain areas, where the climate change
effect can hit much more than in other physical contexts. In mountain basins, the lack of
systematic data and the complexity of the rain/snow phenomena make investigations even more
necessary to figure out the consequences of global warming.
This study explores how the partial contributing area effect due to snow accumulation, on the one
hand, and the basin runoff coefficient, on the other hand, shape the relationship between rainfall
and flood probabilities in high elevation areas. To this aim, the FloodAlp geomorphoclimatic
model (Allamano P. et al., 2009) is used.
The model is based on the derived distribution approach, producing as a result a simplified flood
frequency curve based on the intra-annual variability of the portion of the catchment area covered
by snow, according to simple descriptions of the seasonal variation of the freezing elevation and of
the hypsographic curve of the basin.
To model the basin hypsometric features, we propose the use of a two-parameter Strahler
function, which is a more accurate and alternative formulation to the simple one-parameter
function originally used in the model. The role of the extreme rainfall frequency analysis is also
explicitly analysed, by applying the model using rainfall extremes recorded both in the daily and
24-hours windows. In this application, the only parameter that requires calibration is the runoff
coefficient. Considering recordings of annual maximum daily discharges, the runoff coefficients for
more than 100 gauged basins in north-western Italy have been calibrated. Comparisons are then
possible between the shapes of rainfall and flood frequency distributions within the sample
analysed, that also take into account the basin geomorphoclimatic features. Results of this
application address the selection of relevant characteristics in relation to the impact of climate
change on mountain floods as a result of changes in temperatures and in the statistics of rainfall
extremes
The miRNA Pull Out Assay as a Method to Validate the miR-28-5p Targets Identified in Other Tumor Contexts in Prostate Cancer
miR-28-5p is an intragenic miRNA which is underexpressed in several tumor types showing a tumor suppressor (TS) activity. Routinely, the known miR-28-5p targets are validated in specific tumor contexts but it is unclear whether these targets are also being regulated in other tumor types. To this end, we adopted the miRNA pull out assay to capture the miR-28-5p targets in DU-145 prostate cancer (PCa) cells. Firstly, we demonstrated that miR-28-5p acts as a TS-miRNA in PCa, affecting cell proliferation, survival, and apoptosis. Secondly, we evaluated the enrichment of the 10 validated miR-28-5p targets in the pull out sample. We showed that E2F6, TEX-261, MAPK1, MPL, N4BP1, and RAP1B but not BAG1, OTUB1, MAD2L1, and p21 were significantly enriched, suggesting that not all the miR-28-5p targets are regulated by this miRNA in PCa. We then verified whether the miR-28-5p-interacting targets were regulated by this miRNA. We selected E2F6, the most enriched target in the pull out sample, and demonstrated that miR-28-5p downregulated E2F6 at the protein level suggesting that our approach was effective. In general terms, these findings support the miRNA pull out assay as a useful method to identify context-specific miRNA targets
Water-Soluble Gold Nanoparticles Protected by Fluorinated Amphiphilic Thiolates
The preparation and the properties of gold nanoparticles (Au NPs) protected by perfluorinated amphiphiles are described. The thiols were devised to form a perfluorinated region close to the gold surface and to have a hydrophilic portion in contact with the bulk solvent to impart solubility in water. The monolayer protected clusters were prepared, in an homogeneous phase using sodium thiolates because of the low nucleophilicity of the alpha-perfluorinated thiols, and fully characterized with 1H, 19F NMR spectrometry, IR and UV-vis absorption spectroscopies, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). Au NPs with core diameters ranging from 1.6 to 2.9 nm, depending on the reaction conditions, were obtained. Water-soluble NPs (MPC-F8-PEGs) were obtained with the thiol HS-F8-PEG ending with a short poly(ethylene glycol) unit (PEG-OMe 550), whereas thiols with shorter PEG chains give rise to NPs insoluble in water. MPC-F8-PEGs undergo an exchange reaction with amphiphilic alkyl thiols. ESR investigations, using a hydrophobic radical probe, indicate that the MPC-F8-PEG monolayer shows a greater hydrophobicity compared to the analogous hydrogenated monolayer.
Mechanisms of endothelial cell dysfunction in cystic fibrosis
Although cystic fibrosis (CF) patients exhibit signs of endothelial perturbation, the functions of the cystic fibrosis
conductance regulator (CFTR) in vascular endothelial cells (EC) are poorly defined. We sought to uncover
biological activities of endothelial CFTR, relevant for vascular homeostasis and inflammation. We examined cells
from human umbilical cords (HUVEC) and pulmonary artery isolated from non-cystic fibrosis (PAEC) and CF
human lungs (CF-PAEC), under static conditions or physiological shear. CFTR activity, clearly detected in
HUVEC and PAEC, was markedly reduced in CF-PAEC. CFTR blockade increased endothelial permeability to
macromolecules and reduced trans‑endothelial electrical resistance (TEER). Consistent with this, CF-PAEC displayed
lower TEER compared to PAEC. Under shear, CFTR blockade reduced VE-cadherin and p120 catenin
membrane expression and triggered the formation of paxillin- and vinculin-enriched membrane blebs that
evolved in shrinking of the cell body and disruption of cell-cell contacts. These changes were accompanied by
enhanced release of microvesicles, which displayed reduced capability to stimulate proliferation in recipient EC.
CFTR blockade also suppressed insulin-induced NO generation by EC, likely by inhibiting eNOS and AKT
phosphorylation, whereas it enhanced IL-8 release. Remarkably, phosphodiesterase inhibitors in combination
with a β2 adrenergic receptor agonist corrected functional and morphological changes triggered by CFTR dysfunction
in EC. Our results uncover regulatory functions of CFTR in EC, suggesting a physiological role of CFTR
in the maintenance EC homeostasis and its involvement in pathogenetic aspects of CF. Moreover, our findings
open avenues for novel pharmacology to control endothelial dysfunction and its consequences in CF
The miR-28-5p Targetome Discovery Identified SREBF2 as One of the Mediators of the miR-28-5p Tumor Suppressor Activity in Prostate Cancer Cells
miR-28-5p is downregulated in some tumor tissues in which it has been demonstrated to have tumor suppressor (TS) activity. Here, we demonstrate that miR-28-5p acts as a TS in prostate cancer (PCa) cells affecting cell proliferation/survival, as well as migration and invasion. Using the miRNA pull out assay and next generation sequencing, we collected the complete repertoire of miR-28-5p targets, obtaining a data set (miR-28-5p targetome) of 191 mRNAs. Filtering the targetome with TargetScan 7, PITA and RNA22, we found that 61% of the transcripts had miR-28-5p binding sites. To assign a functional value to the captured transcripts, we grouped the miR-28-5p targets into gene families with annotated function and showed that six transcripts belong to the transcription factor category. Among them we selected SREBF2, a gene with an important role in PCa. We validated miR-28-5p/SREBF2 interaction, demonstrating that SREBF2 inhibition affects almost all the tumor processes altered by miR-28-5p re-expression, suggesting that SREBF2 is an important mediator of miR-28-5p TS activity. Our findings support the identification of the targetome of cancer-related miRNAs as a tool to discover genes and pathways fundamental for tumor development, and potential new targets for anti-tumor therapy
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