Relevance of VEGF and Nephrin Expression in Glomerular Diseases

The glomerular filtration barrier is affected in a large number of acquired and inherited diseases resulting in extensive leakage of plasma albumin and larger proteins, leading to nephrotic syndrome and end-stage renal disease. Unfortunately, the molecular mechanisms governing the development of the nephrotic syndrome remain poorly understood. Here, I give an overview of recent investigations that have focused on characterizing the interrelationships between the slit diaphragm components and podocytes-secreted VEGF, which have a significant role for maintaining the normal podocyte structure and the integrity of the filtering barrier

Dynamin- and Rab5-Dependent Endocytosis of a Ca²⁺-Activated K⁺ Channel, KCa2.3

Regulation of the number of ion channels at the plasma membrane is a critical component of the physiological response. We recently demonstrated that the Ca2+-activated K+ channel, KCa2.3 is rapidly endocytosed and enters a Rab35- and EPI64C-dependent recycling compartment. Herein, we addressed the early endocytic steps of KCa2.3 using a combination of fluorescence and biotinylation techniques. We demonstrate that KCa2.3 is localized to caveolin-rich domains of the plasma membrane using fluorescence co-localization, transmission electron microscopy and co-immunoprecipitation (co-IP). Further, in cells lacking caveolin-1, we observed an accumulation of KCa2.3 at the plasma membrane as well as a decreased rate of endocytosis, as assessed by biotinylation. We also demonstrate that KCa2.3 and dynamin II are co-localized following endocytosis as well as demonstrating they are associated by co-IP. Further, expression of K44A dynamin II resulted in a 2-fold increase in plasma membrane KCa2.3 as well as a 3-fold inhibition of endocytosis. Finally, we evaluated the role of Rab5 in the endocytosis of KCa2.3. We demonstrate that expression of a dominant active Rab5 (Q79L) results in the accumulation of newly endocytosed KCa2.3 on to the membrane of the Rab5-induced vacuoles. We confirmed this co-localization by co-IP; demonstrating that KCa2.3 and Rab5 are associated. As expected, if Rab5 is required for the endocytosis of KCa2.3, expression of a dominant negative Rab5 (S34N) resulted in an approximate 2-fold accumulation of KCa2.3 at the plasma membrane. This was confirmed by siRNA-mediated knockdown of Rab5. Expression of the dominant negative Rab5 also resulted in a decreased rate of KCa2.3 endocytosis. These results demonstrate that KCa2.3 is localized to a caveolin-rich domain within the plasma membrane and is endocytosed in a dynamin- and Rab5-dependent manner prior to entering the Rab35/EPI64C recycling compartment and returning to the plasma membrane. © 2012 Gao et al

CBFA2T3-GLIS2-positive acute myeloid leukaemia. A peculiar paediatric entity

The scenario of paediatric acute myeloid leukaemia (AML), particularly non-Down syndrome acute megakaryoblastic leukaemia (non-DS-AMKL), has been recently revolutionized by the advent of large-scale, genomic sequencing technologies. In this changing landscape, a significantly relevant discovery has been represented by the identification of the CBFA2T3-GLIS2 fusion gene, which is the result of a cryptic inversion of chromosome 16. It is the most frequent chimeric oncogene identified to date in non-DS-AMKL, although it seems not to be exclusively restricted to the French-American-British M7 subgroup. The CBFA2T3-GLIS2 fusion gene characterizes a subtype of leukaemia that is specific to paediatrics, having never been identified in adults. It characterizes an extremely aggressive leukaemia, as the presence of this fusion is associated with a grim outcome in almost all of the case series reported, with overall survival rates ranging between 15% and 30%. Although the molecular basis that underlies this leukaemia subtype is still far from being completely elucidated, unique functional properties induced by CBFA2T3-GLIS2 in the leukaemogenesis driving process have been recently identified. We here review the peculiarities of CBFA2T3-GLIS2-positive AML, describing its intriguing clinical and biological behaviour and providing some challenging targeting opportunities

A comparison of trends in mortality from primary liver cancer and intrahepatic cholangiocarcinoma in Europe

Background To update and compare mortality from primary liver cancer (PLC) and intrahepatic cholangiocarcinoma (ICC) in Europe in 1990-2010. Materials and methods We used data from the World Health Organization (WHO) to compute age-standardized (world population) mortality rates, and used joinpoint analysis to identify substantial changes. Results Between 2002 and 2007, PLC rates in the European Union (EU) declined from 3.9 to 3.6/100 000 men. Around 2007, the highest male rates were in France (6.2/100 000), Spain (4.9), and Italy (4.0), while the lowest ones were in Sweden (1.1), the Netherlands (1.2), and the UK (1.8). In women, mortality was lower (0.8/100 000 in 2007 in the EU), and showed more favourable trends, with a decline of over 2% per year over the last two decades as compared with 0.4% in men, in the EU. In contrast, the EU mortality from ICC increased by around 9% in both sexes from 1990 to 2008, reaching rates of 1.1/100 000 men and 0.75/100 000 women. The highest rates were in UK, Germany, and France (1.2-1.5/100 000 men, 0.8-1.1/100 000 women). Conclusions PLC mortality has become more uniform across Europe over recent years, with an overall decline; in contrast, ICC mortality has substantially increased in most Europ

European cancer mortality predictions for the year 2012

Background: Estimating current cancer mortality figures is important for defining priorities for prevention and treatment. Materials and methods: Using logarithmic Poisson count data joinpoint models on mortality and population data from the World Health Organization database, we estimated numbers of deaths and age-standardized rates in 2012 from all cancers and selected cancer sites for the whole European Union (EU) and its six more populated countries. Results: Cancer deaths in the EU in 2012 are estimated to be 1 283 101 (717 398 men and 565 703 women) corresponding to standardized overall cancer death rates of 139/100 000 men and 85/100 000 women. The fall from 2007 was 10% in men and 7% in women. In men, declines are predicted for stomach (−20%), leukemias (−11%), lung and prostate (−10%) and colorectal (−7%) cancers, and for stomach (−23%), leukemias (−12%), uterus and colorectum (−11%) and breast (−9%) in women. Almost stable rates are expected for pancreatic cancer (+2-3%) and increases for female lung cancer (+7%). Younger women show the greatest falls in breast cancer mortality rates in the EU (−17%), and declines are expected in all individual countries, except Poland. Conclusion: Apart for lung cancer in women and pancreatic cancer, continuing falls are expected in mortality from major cancers in the E

High temperature AlInP X-ray spectrometers

Two custom-made Al0.52In0.48P p+-i-n+ mesa photodiodes with different diameters (217 µm ± 15 µm and 409 µm ± 28 µm) and i layer thicknesses of 6 µm have been electrically characterised over the temperature range 0 °C to 100 °C. Each photodiode was then investigated as a high-temperature-tolerant photon counting X-ray detector by connecting it to a custom-made low-noise charge-sensitive preamplifier and illuminating it with an 55Fe radioisotope X-ray source (Mn Kα = 5.9 keV; Mn Kβ = 6.49 keV). At 100 °C, the best energy resolutions (full width at half maximum at 5.9 keV) achieved using the 217 µm ± 15 µm diameter photodiode and the 409 µm ±28 µm diameter photodiode were 1.31 keV ± 0.04 keV and 1.64 keV ±0.08 keV, respectively. Noise analysis of the system is presented. The dielectric dissipation factor of Al0.52In0.48P was estimated as a function of temperature, up to 100 °C. The results show the performance of the thickest Al0.52In0.48P X-ray detectors so far reported at high temperature. The work has relevance for the development of novel space science instrumentation for use in hot space environments and extreme terrestrial applications

A cryptic alien seaweed spreading in Mediterranean coastal lagoons.

1 - Introductions of exotic macroalgae have increased recently on European shores. Each introductioninvolves at least one vector of transfer. For macroalgae, the potential vectors are aquaculture(intentional or accidental introduction), fouling on hulls, ballast water, aquarium trading, fishingnets.2 - Coastal lagoons, including Venice and Thau Lagoon, developed into major hotspots of marinemacrophyte introductions in the Mediterranean Sea. Moreover, in shallow lagoons and estuaries,eutrophication processes have resulted in the development of macroalgal biomass.3 - The most characteristic species of these macroalgal communities include members of the ulvophyceangenus Ulva L. In foliose Ulvales, simple morphology and anatomy, rampant convergence, remarkabledegrees of phenotypic plasticity in response to environmental factors tend to confound attempts atidentification and make cryptic introduction difficult to detect.4 - During a survey of macroalgal biodiversity in Venice Lagoon, among the pool of exotic speciesfound, there was an Ulva differing from the Atlantic and Mediterranean species in both vegetativeand reproductive features. Detailed observations consented us to identify the taxon as Ulva pertusaKjellman, previously reported in the Mediterranean only for Thau Lagoon

Shot Noise in Linear Macroscopic Resistors

We report on a direct experimental evidence of shot noise in a linear macroscopic resistor. The origin of the shot noise comes from the fluctuation of the total number of charge carriers inside the resistor associated with their diffusive motion under the condition that the dielectric relaxation time becomes longer than the dynamic transit time. Present results show that neither potential barriers nor the absence of inelastic scattering are necessary to observe shot noise in electronic devices.Comment: 10 pages, 5 figure

Electrical and ultraviolet characterization of 4H-SiC Schottky photodiodes

Fabrication and electrical and optical characterization of 4H-SiC Schottky UV photodetectors with nickel silicide interdigitated contacts is reported. Dark capacitance and current measurements as a function of applied voltage over the temperature range 20 °C – 120 °C are presented. The results show consistent performance among devices. Their leakage current density, at the highest investigated temperature (120 °C), is in the range of nA/cm2 at high internal electric field. Properties such as barrier height and ideality factor are also computed as a function of temperature. The responsivities of the diodes as functions of applied voltage were measured using a UV spectrophotometer in the wavelength range 200 nm - 380 nm and compared with theoretically calculated values. The devices had a mean peak responsivity of 0.093 A/W at 270 nm and −15 V reverse bias

Advances in High-Energy-Resolution CdZnTe Linear Array Pixel Detectors with Fast and Low Noise Readout Electronics

Radiation detectors based on Cadmium Zinc Telluride (CZT) compounds are becoming popular solutions thanks to their high detection efficiency, room temperature operation, and to their reliability in compact detection systems for medical, astrophysical, or industrial applications. However, despite a huge effort to improve the technological process, CZT detectors’ full potential has not been completely exploited when both high spatial and energy resolution are required by the application, especially at low energies (<10 keV), limiting their application in energy-resolved photon counting (ERPC) systems. This gap can also be attributed to the lack of dedicated front-end electronics which can bring out the best in terms of detector spectroscopic performances. In this work, we present the latest results achieved in terms of energy resolution using SIRIO, a fast low-noise charge sensitive amplifier, and a linear-array pixel detector, based on boron oxide encapsulated vertical Bridgman-grown B-VB CZT crystals. The detector features a 0.25-mm pitch, a 1-mm thickness and is operated at a −700-V bias voltage. An equivalent noise charge of 39.2 el. r.m.s. (corresponding to 412 eV FWHM) was measured on the test pulser at 32 ns peaking time, leading to a raw resolution of 1.3% (782 eV FWHM) on the 59 keV line at room temperature (+20 °C) using an uncollimated 241Am, largely improving the current state of the art for CZT-based detection systems at such short peaking times, and achieving an optimum resolution of 0.97% (576 eV FWHM) at 1 µs peaking time. The measured energy resolution at the 122 keV line and with 1 µs peaking time of a 57Co raw uncollimated spectrum is 0.96% (1.17 keV). These activities are in the framework of an Italian collaboration on the development of energy-resolved X-ray scanners for material recycling, medical applications, and non-destructive testing in the food industry