Modulation of microRNA editing, expression and processing by ADAR2 deaminase in glioblastoma.

Background: ADAR enzymes convert adenosines to inosines within double-stranded RNAs, including microRNA (miRNA) precursors, with important consequences on miRNA retargeting and expression. ADAR2 activity is impaired in glioblastoma and its rescue has anti-tumoral effects. However, how ADAR2 activity may impact the miRNome and the progression of glioblastoma is not known. Results: By integrating deep-sequencing and array approaches with bioinformatics analyses and molecular studies, we show that ADAR2 is essential to edit a small number of mature miRNAs and to significantly modulate the expression of about 90 miRNAs in glioblastoma cells. Specifically, the rescue of ADAR2 activity in cancer cells recovers the edited miRNA population lost in glioblastoma cell lines and tissues, and rebalances expression of onco-miRNAs and tumor suppressor miRNAs to the levels observed in normal human brain. We report that the major effect of ADAR2 is to reduce the expression of a large number of miRNAs, most of which act as onco-miRNAs. ADAR2 can edit miR-222/221 and miR-21 precursors and decrease the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with important effects on cell proliferation and migration. Conclusions: Our findings disclose an additional layer of complexity in miRNome regulation and provide information to better understand the impact of ADAR2 editing enzyme in glioblastoma. We propose that ADAR2 is a key factor for maintaining edited-miRNA population and balancing the expression of several essential miRNAs involved in cancer

Fano collective resonance as complex mode in a two dimensional planar metasurface of plasmonic nanoparticles

Fano resonances are features in transmissivity/reflectivity/absorption that owe their origin to the interaction between a bright resonance and a dark (i.e., sub-radiant) narrower resonance, and may emerge in the optical properties of planar two-dimensional (2D) periodic arrays (metasurfaces) of plasmonic nanoparticles. In this Letter, we provide a thorough assessment of their nature for the general case of normal and oblique plane wave incidence, highlighting when a Fano resonance is affected by the mutual coupling in an array and its capability to support free modal solutions. We analyze the representative case of a metasurface of plasmonic nanoshells at ultraviolet frequencies and compute its absorption under TE- and TM-polarized, oblique plane-wave incidence. In particular, we find that plasmonic metasurfaces display two distinct types of resonances observable as absorption peaks: one is related to the Mie, dipolar resonance of each nanoparticle; the other is due to the forced excitation of free modes with small attenuation constant, usually found at oblique incidence. The latter is thus an array-induced collective Fano resonance. This realization opens up to manifold flexible designs at optical frequencies mixing individual and collective resonances. We explain the physical origin of such Fano resonances using the modal analysis, which allows to calculate the free modes with complex wavenumber supported by the metasurface. We define equivalent array dipolar polarizabilities that are directly related to the absorption physics at oblique incidence and show a direct dependence between array modal phase and attenuation constant and Fano resonances. We thus provide a more complete picture of Fano resonances that may lead to the design of filters, energy-harvesting devices, photodetectors, and sensors at ultraviolet frequencies.Comment: 6 pages, 5 figure

Transport coefficients from the Boson Uehling-Uhlenbeck Equation

We derive microscopic expressions for the bulk viscosity, shear viscosity and thermal conductivity of a quantum degenerate Bose gas above $T_C$, the critical temperature for Bose-Einstein condensation. The gas interacts via a contact potential and is described by the Uehling-Uhlenbeck equation. To derive the transport coefficients, we use Rayleigh-Schrodinger perturbation theory rather than the Chapman-Enskog approach. This approach illuminates the link between transport coefficients and eigenvalues of the collision operator. We find that a method of summing the second order contributions using the fact that the relaxation rates have a known limit improves the accuracy of the computations. We numerically compute the shear viscosity and thermal conductivity for any boson gas that interacts via a contact potential. We find that the bulk viscosity remains identically zero as it is for the classical case.Comment: 10 pages, 2 figures, submitted to Phys. Rev.

Hyperbolic Balance Laws with a Non Local Source

This paper is devoted to hyperbolic systems of balance laws with non local source terms. The existence, uniqueness and Lipschitz dependence proved here comprise previous results in the literature and can be applied to physical models, such as Euler system for a radiating gas and Rosenau regularization of the Chapman-Enskog expansion.Comment: 26 page

Rapid determination of anti-estrogens by gas chromatography/mass spectrometry in urine: Method validation and application to real samples

AbstractA fast screening protocol was developed for the simultaneous determination of nine anti-estrogenic agents (aminoglutethimide, anastrozole, clomiphene, drostanolone, formestane, letrozole, mesterolone, tamoxifen, testolactone) plus five of their metabolites in human urine. After an enzymatic hydrolysis, these compounds can be extracted simultaneously from urine with a simple liquid–liquid extraction at alkaline conditions. The analytes were subsequently analyzed by fast-gas chromatography/mass spectrometry (fast-GC/MS) after derivatization. The use of a short column, high-flow carrier gas velocity and fast temperature ramping produced an efficient separation of all analytes in about 4min, allowing a processing rate of 10samples/h. The present analytical method was validated according to UNI EN ISO/IEC 17025 guidelines for qualitative methods. The range of investigated parameters included the limit of detection, selectivity, linearity, repeatability, robustness and extraction efficiency. High MS-sampling rate, using a benchtop quadrupole mass analyzer, resulted in accurate peak shape definition under both scan and selected ion monitoring modes, and high sensitivity in the latter mode. Therefore, the performances of the method are comparable to the ones obtainable from traditional GC/MS analysis. The method was successfully tested on real samples arising from clinical treatments of hospitalized patients and could profitably be used for clinical studies on anti-estrogenic drug administration

Viscoelastic optical nonlocality of low-loss epsilon-near-zero nanofilms

Optical nonlocalities are elusive and hardly observable in traditional plasmonic materials like noble and alkali metals. Here we report experimental observation of viscoelastic nonlocalities in the infrared optical response of doped cadmium-oxide, epsilon-near-zero nanofilms. The nonlocality is detectable thanks to the low damping rate of conduction electrons and the virtual absence of interband transitions at infrared wavelengths. We describe the motion of conduction electrons using a hydrodynamic model for a viscoelastic fluid, and find excellent agreement with experimental results. The electrons elasticity blue-shifts the infrared plasmonic resonance associated with the main epsilon-near-zero mode, and triggers the onset of higher-order resonances due to the excitation of electron-pressure modes above the bulk plasma frequency. We also provide evidence of the existence of nonlocal damping, i.e., viscosity, in the motion of optically-excited conduction electrons using a combination of spectroscopic ellipsometry data and predictions based on the viscoelastic hydrodynamic model.Comment: 19 pages, 5 figure