Role of metformin and AKT axis modulation in the reversion of hypoxia induced TMZ-resistance in glioma cells

Hypoxia is a key driver of tumor adaptation promoting tumor progression and resistance to therapy. Hypoxia related pathways might represent attractive targets for the treatment of Glioblastoma Multiforme (GBM), that up to date is characterized by a poor prognosis. Primary aim of this study was to investigate the role of hypoxia and hypoxia-related modifications in the effect of temozolomide (TMZ) given alone or in association with the antidiabetic agent Metformin (MET) or the PI3K/mTOR blocker, BEZ235. The study was conducted in the TMZ responsive U251 and resistant T98 GBM cells. Our results showed that during hypoxia, TMZ plus MET reduced viability of U251 cells affecting also CD133 and CD90 expressing cells. This effect was associated with a reduction of HIF-1\u3b1 activity, VEGF release and AKT activation. In T98 TMZ-resistant cells, TMZ plus MET exerted similar effects on HIF-1\u3b1. However, in this cell line, TMZ plus MET failed to reduce CD133 positive cells and AKT phosphorylation. Nevertheless, the administration of the dual PI3K/mTOR inhibitor BEZ235 potentiated the effect of TMZ plus MET on cell viability, inducing a pro-apoptotic phenotype during hypoxic condition also in T98 cells, suggesting the block of the PI3K/AKT/mTOR pathway as a complementary target to further overcome GBM resistance during hypoxia. In conclusion, we proposed TMZ plus MET as suitable treatment to revert TMZ-resistance also during hypoxia, an effect potentiated by the inhibition of PI3K/mTOR axis

Atividade antioxidante e compostos fenólicos de cinco acessos de pimentas Capsicum chinense.

Pimentas além de serem popularmente utilizadas como condimentos, representam uma fonte significativa de compostos antioxidantes. A espécie de pimentas Capsicum chinense, originária do Brasil apresenta mais de 40 variedades, sendo que muitas ainda são desconhecidas quanto as suas potencialidades. Neste trabalho foram caracterizados quanto à atividade antioxidante e ao teor de compostos fenólicos, cinco genótipos de pimenta C. chinense do Banco Ativo de Germoplasma da Embrapa Amazônia Oriental, visando identificar as variedades promissoras para serem utilizadas em futuros programas de melhoramento genético. A atividade antioxidante foi determinada através dos ensaios de DPPH e ABTS e os compostos fenólicos através do reagente de Follin Ciocalteau. Em relação ao teor de compostos fenólicos a variedade (PCL-02) destacou-se das demais com 12710 mgEAG/100g de pimenta. Houve diferença significativa ao nível de 5% nos resultados das três análises para as cinco variedades de pimenta analisada, demonstrando que a intensidade desta ação antioxidante é diferenciada em cada uma das variedades

A methodology to select galaxies just after the quenching of star formation

We propose a new methodology aimed at finding star-forming galaxies in the phase which immediately follows the star-formation (SF) quenching, based on the use of high- to lowionization emission line ratios. These ratios rapidly disappear after the SF halt, due to the softening of the UV ionizing radiation. We focus on [O III] λ5007/Hα and [Ne III] λ3869/[O II] λ3727, studying them with simulations obtained with the CLOUDY photoionization code. If a sharp quenching is assumed, we find that the two ratios are very sensitive tracers as they drop by a factor of ~ 10 within ~10 Myr from the interruption of the SF; instead, if a smoother and slower SF decline is assumed (i.e. an exponentially declining SF history with e-folding time τ = 200 Myr), they decrease by a factor of ~2 within ~80 Myr. We mitigate the ionization- metallicity degeneracy affecting our methodology using pairs of emission line ratios separately related to metallicity and ionization, adopting the [N II] λ6584/[O II] λ3727 ratio as metallicity diagnostic. Using a Sloan Digital Sky Survey galaxy sample, we identify 10 examples among the most extreme quenching candidates within the [O III] λ5007/Hα versus [N II] λ6584/[O II] λ3727 plane, characterized by low [O III] λ5007/Hα, faint [Ne III] λ3869, and by blue dust-corrected spectra and (u - r) colours, as expected if the SF quenching has occurred in the very recent past. Our results also suggest that the observed fractions of quenching candidates can be used to constrain the quenching mechanism at work and its time-scales

Amine-Gold Linked Single-Molecule Junctions: Experiment and Theory

The measured conductance distribution for single molecule benzenediamine-gold junctions, based on 59,000 individual conductance traces recorded while breaking a gold point contact in solution, has a clear peak at 0.0064 G$_{0}$ with a width of $\pm$ 40%. Conductance calculations based on density functional theory (DFT) for 15 distinct junction geometries show a similar spread. Differences in local structure have a limited influence on conductance because the amine-Au bonding motif is well-defined and flexible. The average calculated conductance (0.046 G$_{0}$) is seven times larger than experiment, suggesting the importance of many-electron corrections beyond DFT

Passive galaxies as tracers of cluster environments at z~2

Even 10 billion years ago, the cores of the first galaxy clusters are often found to host a characteristic population of massive galaxies with already suppressed star formation. Here we search for distant cluster candidates at z~2 using massive passive galaxies as tracers. With a sample of ~40 spectroscopically confirmed passive galaxies at 1.3<z<2.1, we tune photometric redshifts of several thousands passive sources in the full 2 sq.deg. COSMOS field. This allows us to map their density in redshift slices, probing the large scale structure in the COSMOS field as traced by passive sources. We report here on the three strongest passive galaxy overdensities that we identify in the redshift range 1.5<z<2.5. While the actual nature of these concentrations is still to be confirmed, we discuss their identification procedure, and the arguments supporting them as candidate galaxy clusters (likely mid-10^13 M_sun range). Although this search approach is likely biased towards more evolved structures, it has the potential to select still rare, cluster-like environments close to their epoch of first appearance, enabling new investigations of the evolution of galaxies in the context of structure growth.Comment: 5 pages, 5 figures; A&A Letters, in pres

Validation of an Engineered Cell Model for In Vitro and In Vivo HIF-1 alpha Evaluation by Different Imaging Modalities

n/

Quantifying the importance of plastic pollution for the dissemination of human pathogens: The challenges of choosing an appropriate 'control' material

Discarded plastic wastes in the environment are serious challenges for sustainable waste management and for the delivery of environmental and public health. Plastics in the environment become rapidly colonised by microbial biofilm, and importantly this so-called ‘plastisphere’ can also support, or even enrich human pathogens. The plastisphere provides a protective environment and could facilitate the increased survival, transport and dissemination of human pathogens and thus increase the likelihood of pathogens coming into contact with humans, e.g., through direct exposure at beaches or bathing waters. However, much of our understanding about the relative risks associated with human pathogens colonising environmental plastic pollution has been inferred from taxonomic identification of pathogens in the plastisphere, or laboratory experiments on the relative behaviour of plastics colonised by human pathogens. There is, therefore, a pressing need to understand whether plastics play a greater role in promoting the survival and dispersal of human pathogens within the environment compared to other substrates (either natural materials or other pollutants). In this paper, we consider all published studies that have detected human pathogenic bacteria on the surfaces of environmental plastic pollution and critically discuss the challenges of selecting an appropriate control material for plastisphere experiments. Whilst it is clear there is no ‘perfect’ control material for all plastisphere studies, understanding the context-specific role plastics play compared to other substrates for transferring human pathogens through the environment is important for quantifying the potential risk that colonised plastic pollution may have for environmental and public health

New constraints on cosmological parameters and neutrino properties using the expansion rate of the Universe to z~1.75

We have assembled a compilation of observational Hubble parameter measurements estimated with the differential evolution of cosmic chronometers, in the redshift range 0<z<1.75. This sample has been used, in combination with CMB data and with the most recent estimate of the Hubble constant H_0, to derive new constraints on several cosmological parameters. The new Hubble parameter data are very useful to break some of the parameter degeneracies present in CMB-only analysis, and to constrain possible deviations from the standard (minimal) flat \Lambda CDM model. The H(z) data are especially valuable in constraining \Omega_k and \Omega_DE in models that allow a variation of those parameters, yielding constraints that are competitive with those obtained using Supernovae and/or baryon acoustic oscillations. We also find that our H(z) data are important to constrain parameters that do no affect directly the expansion history, by breaking or reducing degeneracies with other parameters. We find that Nrel=3.45\pm0.33 using WMAP 7-years data in combination with South Pole Telescope data and our H(z) determinations (Nrel=3.71\pm0.45 using Atacama Cosmology Telescope data instead of South Pole Telescope). We exclude Nrel>4 at 95% CL (74% CL) using the same datasets combinations. We also put competitive limits on the sum of neutrino masses, \Sigma m_\nu<0.24 eV at 68% confidence level. These results have been proven to be extremely robust to many possible systematic effects, such as the initial choice of stellar population synthesis model adopted to estimate H(z) and the progenitor-bias.Comment: 18 pages, 17 figures, 7 tables, published in JCAP. It is a companion to Moresco et al. (2012a, http://arxiv.org/abs/1201.3609) and Jimenez et al. (2012, http://arxiv.org/abs/1201.3608). The H(z) data can be downloaded at http://www.physics-astronomy.unibo.it/en/research/areas/astrophysics/cosmology-with-cosmic-chronometer