Exposure to bisphenol-a during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice

sem informaçãoBisphenol-A (BPA) is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β-cell function and gene expression in the major peripheral organs that control energy flux: white adipose tissue (WAT), the liver and skeletal muscle, in male offspring 17 and 28 weeks old. Pregnant mice were treated with a subcutaneous injection of 10 µg/kg/day of BPA or a vehicle from day 9 to 16 of pregnancy. One month old offspring were divided into four different groups: vehicle treated mice that ate a normal chow diet (Control group); BPA treated mice that also ate a normal chow diet (BPA); vehicle treated animals that had a high fat diet (HFD) and BPA treated animals that were fed HFD (HFD-BPA). The BPA group started to gain weight at 18 weeks old and caught up to the HFD group before week 28. The BPA group as well as the HFD and HFD-BPA ones presented fasting hyperglycemia, glucose intolerance and high levels of non-esterified fatty acids (NEFA) in plasma compared with the Control one. Glucose stimulated insulin release was disrupted, particularly in the HFD-BPA group. In WAT, the mRNA expression of the genes involved in fatty acid metabolism, Srebpc1, Pparα and Cpt1β was decreased by BPA to the same extent as with the HFD treatment. BPA treatment upregulated Pparγ and Prkaa1 genes in the liver; yet it diminished the expression of Cd36. Hepatic triglyceride levels were increased in all groups compared to control. In conclusion, male offspring from BPA-treated mothers presented symptoms of diabesity. This term refers to a form of diabetes which typically develops in later life and is associated with obesity.Bisphenol-A (BPA) is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β96113sem informaçãosem informaçãosem informaçã

Production of unstable heavy neutrinos in proto-neutron stars

We discuss the production of a class of heavy sterile neutrinos nu(h) in proto-neutron stars. The neutrinos, of mass around 50 MeV, have a negligible mixing with the active species but relatively large dimension-5 electromagnetic couplings. In particular, a magnetic dipole moment mu approximate to 10(-6) GeV-1 implies that they are thermally produced through e(+)e(-) -> (nu) over bar (h)nu(h) in the early phase of the core collapse, whereas a heavy-light transition moment mu(tr) approximate to 10(-8) GeV-1 allows their decay nu(h) -> nu i gamma with a lifetime around 10(-3) s. This type of electromagnetic couplings has been recently proposed to explain the excess of electron-like events in baseline experiments. We show that the production and decay of these heavy neutrinos would transport energy from the central regions of the star to distances d approximate to 400 km, providing a very efficient mechanism to enhance the supernova shock front and heat the material behind it.Open Access funded by SCOAP³ - Sponsoring Consortium for Open Access Publishing in Particle Physics.This work has been supported by MINECO of Spain (FPA2013-47836, FIS2012-30926) and Consolider-IngenioMul-tidarkCSD2009-00064) and by Junta de Andalucía (FQM225, FQM101,3048)

Preliminary results on the application of the aminoacid racemization technique in the Murcia Region (SE Iberian Peninsula) and their interest in paleoseismological research

Geochronology is a critical issue in paleoseismological research. The aminoacid racemization technique shows important advantages respect to more traditional dating methods; not just for the lower costs and promptness, also because the object to analyze is relatively frequent, in this study: terrestrial gastropods. Furthermore, the costs of the analysis are by far faster and cheaper compared to other dating techniques. Racemization results allow comparing the relative age from different sedimentary units from one trench to another.Additionally, the racemization technique can also be used as a geochronological tool, provided a calibration curve has been first obtained for the particular climate for the area and, ideally, for a particular genus. In this study we show the results obtained from the analysis of 40 samples of terrestrial gastropods from 7 different trenches located in the Murcia Region (SE Spain). Making use of the D/L ratio of aspartic acid we show the coherence found between relative stratigraphic ages and the racemization age. Finally, we show a provisional conversion equation between age of racemization, obtained from Torres et al. (1997) algorithm, and the likely age of the samEl control geocronológico es una cuestión crítica en los estudios de paleosismología. La técnica de racemización de aminoácidos ofrece importantes ventajas respecto a otros métodos de datación, tanto en los costes y rapidez, como en la facilidad de encontrar el objeto de análisis; en este estudio, gasterópodos terrestres. Los resultados permiten comparar la edad relativa entre unidades sedimentarias diferentes de unas zanjas a otras. La técnica de racemización también es una herramienta geocronológica, si bien es necesario primero establecer una curva de calibración para el ambiente climático de la zona e, idealmente, para un género concreto. En este estudio se muestran los resultados obtenidos en 40 muestras de gasterópodos terrestres recogidas en 7 zanjas de investigación paleosismológica en la Región de Murcia. Haciendo uso de la relación D/L del ácido aspártico mostramos la coherencia entre las edades relativas estratigráficas y su edad de racemización. Finalmente, proponemos una relación provisional de conversión entre las edades de racemización obtenidas por el algoritmo de Torres et al. (1997) para gasterópodos de la zona central de la Península Ibérica y la edad probable de las muestra

Variability of the aminoacid racemization relation in a group of Quaternary continental gastropods in Murcia (Spain)

La aplicación de los resultados de un análisis de racemización de aminoácidos en geocronología ofrece importantes ventajas respecto a otras técnicas, al ser esta más rápida y económica. Sin embargo, como con cualquier otra técnica, la racemización no está exenta de fuentes de incertidumbres que deben ser analizadas previamente a la interpretación. En este trabajo se exponen los resultados obtenidos del análisis de racemización de un grupo de 25 gasterópodos continentales fósiles hallados en una excavación de investigación paleosismológica en el municipio de Alhama de Murcia. En particular se compara la ratio entre aminoácidos con estructura dextrógira y levógira (relación D/L) de los ácidos aspártico y glutámico. En primer lugar, se revisan las principales fuentes de incertidumbre que afectan a la racemización. Seguidamente se muestra la metodología empleada para descartar muestras y, finalmente, se aborda una interpretación preliminar de los resultados en relación con la estratigrafía local y la paleosismologíaThe use of the amino acid racemization technique in geochronology offers a great advantage compared to other techniques, as racemization analyses are usually much faster and cheaper. However, as in any other technique, amino acid racemization is subject to a number of uncertainties, which have to be thoroughly analysed previously to any interpretation of the data. In this work, we present the results obtained in a group of 25 continental gastropods found in a paleoseismological trench in Alhama de Murcia (Betic Range, Spain). We carry out the comparison of dextrorotatory and levorotatory configuration (relation D/L) of the aspartic and glutamic acids. First, we review the different sources of uncertainty in the racemization process. Subsequently we show the methodology followed for discarding samples and, finally, we interpret in preliminary terms the results in relation to the local stratigraphy and paleoseismolog

A Search for Electron Antineutrino Appearance at the Δm2∼\Delta m^2 \sim 1 eV2\mathrm{eV}^{2} Scale

The MiniBooNE Collaboration reports initial results from a search for $\bar{\nu}_{\mu}\to\bar{\nu}_e$ oscillations. A signal-blind analysis was performed using a data sample corresponding to $3.39 \times 10^{20}$ protons on target. The data are consistent with background prediction across the full range of neutrino energy reconstructed assuming quasielastic scattering, $200 < E_{\nu}^{QE} < 3000$ MeV: 144 electron-like events have been observed in this energy range, compared to an expectation of $139.2 \pm 17.6$ events. No significant excess of events has been observed, both at low energy, 200-475 MeV, and at high energy, 475-1250 MeV. The data are inconclusive with respect to antineutrino oscillations suggested by data from the Liquid Scintillator Neutrino Detector at Los Alamos National Laboratory.Comment: 5 pages, 3 figures, 2 table

Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed

BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3' untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity. RESULTS: The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed. CONCLUSION: In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype

Therapeutic Benefit of Radial Optic Neurotomy in a Rat Model of Glaucoma

Radial optic neurotomy (RON) has been proposed as a surgical treatment to alleviate the neurovascular compression and to improve the venous outflow in patients with central retinal vein occlusion. Glaucoma is characterized by specific visual field defects due to the loss of retinal ganglion cells and damage to the optic nerve head (ONH). One of the clinical hallmarks of glaucomatous neuropathy is the excavation of the ONH. The aim of this work was to analyze the effect of RON in an experimental model of glaucoma in rats induced by intracameral injections of chondroitin sulfate (CS). For this purpose, Wistar rats were bilaterally injected with vehicle or CS in the eye anterior chamber, once a week, for 10 weeks. At 3 or 6 weeks of a treatment with vehicle or CS, RON was performed by a single incision in the edge of the neuro-retinal ring at the nasal hemisphere of the optic disk in one eye, while the contralateral eye was submitted to a sham procedure. Electroretinograms (ERGs) were registered under scotopic conditions and visual evoked potentials (VEPs) were registered with skull-implanted electrodes. Retinal and optic nerve morphology was examined by optical microscopy. RON did not affect the ocular hypertension induced by CS. In eyes injected with CS, a significant decrease of retinal (ERG a- and b-wave amplitude) and visual pathway (VEP N2-P2 component amplitude) function was observed, whereas RON reduced these functional alterations in hypertensive eyes. Moreover, a significant loss of cells in the ganglion cell layer, and Thy-1-, NeuN- and Brn3a- positive cells was observed in eyes injected with CS, whereas RON significantly preserved these parameters. In addition, RON preserved the optic nerve structure in eyes with chronic ocular hypertension. These results indicate that RON reduces functional and histological alterations induced by experimental chronic ocular hypertension

The MiniBooNE Detector

The MiniBooNE neutrino detector was designed and built to look for muon-neutrino to electron-neutrino oscillations in the mixing parameter space region where the LSND experiment reported a signal. The MiniBooNE experiment used a beam energy and baseline that were an order of magnitude larger than those of LSND so that the backgrounds and systematic errors would be completely different. This paper provides a detailed description of the design, function, and performance of the MiniBooNE detector.Comment: 46 pages, 21 figure

A search for muon neutrino and antineutrino disappearance in MiniBooNE

The MiniBooNE Collaboration reports a search for \numu and \numubar disappearance in the \dmsq region of a few \evsq. These measurements are important for constraining models with extra types of neutrinos, extra dimensions an d CPT violation. Fits to the shape of the \numu and \numubar energy spectra reveal no evidence for disappearance at 90% confidence level (CL) in either mode. This is the first test of \numubar disappearance between \dmsq=0.1-10\evsq.Comment: 10 pages, 3 figures, submitted to PR