Annexin 2A sustains glioblastoma cell dissemination and proliferation.

Glioblastoma (GBM) is the most devastating tumor of the brain, characterized by an almost inevitable tendency to recur after intensive treatments and a fatal prognosis. Indeed, despite recent technical improvements in GBM surgery, the complete eradication of cancer cell disseminated outside the tumor mass still remains a crucial issue for glioma patients management. In this context, Annexin 2A (ANXA2) is a phospholipid-binding protein expressed in a variety of cell types, whose expression has been recently associated with cell dissemination and metastasis in many cancer types, thus making ANXA2 an attractive putative regulator of cell invasion also in GBM.Here we show that ANXA2 is over-expressed in GBM and positively correlates with tumor aggressiveness and patient survival. In particular, we associate the expression of ANXA2 to a mesenchymal and metastatic phenotype of GBM tumors. Moreover, we functionally characterized the effects exerted by ANXA2 inhibition in primary GBM cultures, demonstrating its ability to sustain cell migration, matrix invasion, cytoskeletal remodeling and proliferation. Finally, we were able to generate an ANXA2-dependent gene signature with a significant prognostic potential in different cohorts of solid tumor patients, including GBM.In conclusion, we demonstrate that ANXA2 acts at multiple levels in determining the disseminating and aggressive behaviour of GBM cells, thus proving its potential as a possible target and strong prognostic factor in the future management of GBM patients

Precipitation products from the hydrology SAF

Abstract. The EUMETSAT Satellite Application Facility on Support to Operational Hydrology and Water Management (H-SAF) was established by the EUMETSAT Council on 3 July 2005, starting activity on 1 September 2005. The Italian Meteorological Service serves as Leading Entity on behalf of twelve European member countries. H-SAF products include precipitation, soil moisture and snow parameters. Some products are based only on satellite observations, while other products are based on the assimilation of satellite measurements/products into numerical models. In addition to product development and generation, H-SAF includes a product validation program and a hydrological validation program that are coordinated, respectively, by the Italian Department of Civil Protection and by the Polish Institute of Meteorology and Water Management. The National Center of Aeronautical Meteorology and Climatology (CNMCA) of the Italian Air Force is responsible for operational product generation and dissemination. In this paper we describe the H-SAF precipitation algorithms and products, which have been developed by the Italian Institute of Atmospheric Sciences and Climate (in collaboration with the international community) and by CNMCA during the Development Phase (DP, 2005–2010) and the first Continuous Development and Operations Phase (CDOP-1, 2010–2012). The precipitation products are based on passive microwave measurements obtained from radiometers onboard different sun-synchronous low-Earth-orbiting satellites (especially, the SSM/I and SSMIS radiometers onboard DMSP satellites and the AMSU-A + AMSU-B/MHS radiometer suites onboard EPS-MetOp and NOAA-POES satellites), as well as on combined infrared/passive microwave measurements in which the passive microwave precipitation estimates are used in conjunction with SEVIRI images from the geostationary MSG satellite. Moreover, the H-SAF product generation and dissemination chain and independent product validation activities are described. Also, the H-SAF program and its associated activities that currently are being carried out or are planned to be performed within the second CDOP phase (CDOP-2, 2012–2017) are presented in some detail. Insofar as CDOP-2 is concerned, it is emphasized that all algorithms and processing schemes will be improved and enhanced so as to extend them to satellites that will be operational within this decade – particularly the geostationary Meteosat Third Generation satellites and the low-Earth-orbiting Core Observatory of the international Global Precipitation Measurement mission. Finally, the role of H-SAF within the international science and operations community is explained.</p

Synthesis and Biological Evaluation of 2-Methyl-4,5-Disubstituted Oxazoles as a Novel Class of Highly Potent Antitubulin Agents

Antimitotic agents that interfere with microtubule formation are one of the major classes of cytotoxic drugs for cancer treatment. Multiple 2-methyl-4-(3′,4′,5′-trimethoxyphenyl)-5-substituted oxazoles and their related 4-substituted-5-(3′,4′,5′-trimethoxyphenyl) regioisomeric derivatives designed as cis-constrained combretastatin A-4 (CA-4) analogues were synthesized and evaluated for their antiproliferative activity in vitro against a panel of cancer cell lines and, for selected highly active compounds, interaction with tubulin, cell cycle effects and in vivo potency. Both these series of compounds were characterized by the presence of a common 3′,4′,5′-trimethoxyphenyl ring at either the C-4 or C-5 position of the 2-methyloxazole ring. Compounds 4g and 4i, bearing a m-fluoro-p-methoxyphenyl or p-ethoxyphenyl moiety at the 5-position of 2-methyloxazole nucleus, respectively, exhibited the greatest antiproliferative activity, with IC50 values of 0.35-4.6 nM (4g) and 0.5–20.2 nM (4i), which are similar to those obtained with CA-4. These compounds bound to the colchicine site of tubulin and inhibited tubulin polymerization at submicromolar concentrations. Furthermore, 4i strongly induced apoptosis that follows the mitochondrial pathway. In vivo, 4i in a mouse syngeneic model demonstrated high antitumor activity which significantly reduced the tumor mass at doses ten times lower than that required for CA-4P, suggesting that 4i warrants further evaluation as a potential anticancer drug

A composite approach to produce reference datasets for extratropical cyclone tracks: application to Mediterranean cyclones

Many cyclone detection and tracking methods (CDTMs) have been developed in the past to study the climatology of extratropical cyclones. However, all CDTMs have different approaches in defining and tracking cyclone centers. This naturally leads to cyclone track climatologies with inconsistent physical characteristics. More than that, it is typical for CDTMs to produce a non-negligible number of tracks of weak atmospheric features, which do not correspond to large-scale or mesoscale vortices and can differ significantly between CDTMs. Lack of consensus in CDTM outputs and the inclusion of significant numbers of uncertain tracks therein have long prohibited the production of a commonly accepted reference dataset of extratropical cyclone tracks. Such a dataset could allow comparable results on the analysis of storm track climatologies and could also contribute to the evaluation and improvement of CDTMs. To cover this gap, we present a new methodological approach that combines overlapping tracks from different CDTMs and produces composite tracks that concentrate the agreement of more than one CDTM. In this study we apply this methodology to the outputs of 10 well-established CDTMs which were originally applied to ERA5 reanalysis in the 42-year period of 1979–2020. We tested the sensitivity of our results to the spatiotemporal criteria that identify overlapping cyclone tracks, and for benchmarking reasons, we produced five reference datasets of subjectively tracked cyclones. Results show that climatological numbers of composite tracks are substantially lower than the ones of individual CDTMs, while benchmarking scores remain high (i.e., counting the number of subjectively tracked cyclones captured by the composite tracks). Our results show that composite tracks tend to describe more intense and longer-lasting cyclones with more distinguished early, mature and decay stages than the cyclone tracks produced by individual CDTMs. Ranking the composite tracks according to their confidence level (defined by the number of contributing CDTMs), it is shown that the higher the confidence level, the more intense and long-lasting cyclones are produced. Given the advantage of our methodology in producing cyclone tracks with physically meaningful and distinctive life stages, we propose composite tracks as reference datasets for climatological research in the Mediterranean. The Supplement provides the composite Mediterranean tracks for all confidence levels, and in the conclusion we discuss their adequate use for scientific research and applications.</p

Chemical characterization of cloud episodes at a ridge site in Tuscan Appennines, Italy

Cloudwater samples were collected from November 1992 to March 1995 in Vallombrosa, a mountain site of the Tuscan Apennines (central Italy). Chemical analyses show that all examined inorganic ions contributed significantly to the total ionic content (TIC). The ratio SO4/NO4 ranged from 0.92 to 3.46 and was > 1 for 86% of samples. There is a wide range in the chemical composition of the cloudwater. The total ionic content ranged from 640 to 7476 Aeq l 1 and pH from 3.17 to 6.22. The liquid water content (LWC) ranged from 0.06 to 0.94 g m 3 and electrical conductivity from 47 to 485 AV 1. The total ionic content decreases while the liquid water content increases. Also analyzed were soluble trace metals (Fe, Pb, Cu, Mn, Cd, Al), synthetic anionic surfactants and the methanesulphonic acid. Chemical analyses evidenced in some cases a high concentration of organic matter. The meteorological analysis for a few samples of individual passages was carried out for the possibility of establishing a correspondence between meteorological events and chemical composition. The sources (marine, crustal and anthropogenic) of chemical components were deduced

Cloud cover associated to cut-off low systems in the Mediterranean region

Cut-off low (COL) are middle and upper troposphere closed cyclonically circulating eddies isolated from the main westerly stream; they are common features of Mediterranean meteorology in warm month and are often related to sever weather. Ten years (1992-2001) of warm season ERA-40 reanalysis, available every six hours on 2.5°x2.5° grid, are processed to extract a database of cut-off low occurrence in the Mediterranean basin and continental Europe. The cloud structures related to the COL are analyzed using International Satellite Cloud Climatology Project DX data available every 3 hours on a 30x30 km2 grid. For each COL occurrence, the size of the related cloud shield is estimated, and the mean optical depth and cloud top height computed. Cloud patterns are studied for different COL classes according to their vertical characteristics. Out of a total of 273 COL selected episodes, for about the two thirds (184) the cloud analysis is possible. For remaining third of the events the analysis is not carried out because it is not possible to automatically isolate the cloud cover to be associated to a given COL. For 23 COL systems analyzed no cloudiness is associated at any stage of the development, while for about 20 COL events the size of the cloud structure exceeds few millions of square kilometres. The cloudiness size is related to the vertical structure of the COL: large size are found for those systems that show a corresponding depression at the ground, small size or no cloudiness are found for systems dynamically confined to upper tropospheric levels

Multiparametric radar/microwave precipitation retrieval

The use of polarisation difference over the land for three cases of different nature has been investigated: Poldirad (14/07/1997, strong convective event), Graz (10/07/1997, convective event) and Chilbolton (27/06/1997, stratified event). The correlation between vertical and horizontal polarisation Tbs differences at 85 and 19 GHz and ZH and ZDR as measured by the available radar has been evaluated. The radar domain has been classified in three rain classes by means of the ZH values: no rain (030 dBZ). It was found that the 19 GHz polarisation differences decrease when Zdr increase. On the contrary, 85 GHz channels Tb differences are not related to Zdr variations. At 85 GHz the increase of Zdr results in an average increase of the polarisation difference from the satellite; this implies a rather strong correlation between the rain layer at the ground (as seen by radar) and the ice layer on the top of the cloud as seen at 85 GHz

Drop Size Distribution over the Tibetan Plateau.

A disdrometric campaign has been carried out over the Tibetan Plateau from November 2009 to September 2010 in the frame of CEOP-AEGIS, a Collaborative Project funded under FP7 . Three PLUDIX X-band disdrometers have been installed in Lhasa, Linzhi and Namco in the eastern part of the Plateau, to measure Drop Size Distribution (DSD) of solid and liquid precipitation with two aims: 1) to study the precipitation characteristics over the Plateau and 2) to provide data for weather ground radar calibration. PLUDIX estimates DSD and rainfall-rate measuring the Doppler frequency shift between the radiation transmitted and received, backscattered by falling hydrometeors. Given the low air density at high elevation (ranging from 3600 to 4200 m a.s.l. in the experimental sites), the retrieval algorithms were modified, taking into account the relationship between the drop diameter and the drop speed as proposed by Beard (1976). One year of data has been analyzed: a total of more than 80 precipitating events were collected in the three sites. The rain events (about 50 events in the three sites) were analyzed in terms of both DSD and rainfall-rate, while the rain-snow, snow and ice-crystals events (about 35 events in the three sites) were detected and analyzed in terms of Pludix power spectrum

Precipitation classification at mid-latitudes in terms of drop size distribution parameters

The drop size distribution (DSD) is a fundamental property of rainfall because the shape of the distribution re- flects the physics of rain formation processes. Given the lack of studies on the DSD at mid-latitudes, the present work fo- cuses on the microphysical characterization of precipitation events occurring in Italy, using two different types of dis- drometer. A large number of different rain events was col- lected: they underwent microphysical analysis by computing the Z-R relationships, observing the average DSDs and DSD parameters, fitting the real distribution for different rainfall rate categories and applying convective (C) – stratiform (S) discrimination algorithms. A general agreement with past works at mid-latitudes is found both in the Z-R relationship and in DSD parameters. The rain distribution is well de- scribed by a gamma DSD and only in some cases (especially the light rain events) by an exponential DSD. Marked differ- ences are observed in DSD parameters and Z-R relationships between C and S episodes. The use of disdrometers for ar- eas covered by multiparametric radar is suggested and will be performed in the near future