Co-overexpression of bcl-2 and c-myc in uterine cervix carcinomas and premalignant lesions

To establish the role of co-overexpression of bcl-2 and c-myc protooncogenes in uterine cervix carcinogenesis, we examined 138 tissue samples of low grade cervical squamous intraepithelial lesions (SIL), high grade SIL, portio vaginalis uteri (PVU) carcinoma in situ and PVU invasive carcinoma, stage IA-IIA (study group) and 36 samples without SIL or malignancy (control group). The expression of bcl-2 and c-myc was detected immunohistochemically using a monoclonal antibody. Fisher's exact test (P<0.05) was used to assess statistical significance. Overexpression of bcl-2 was found to increase in direct relation to the grade of the cervical lesions. High sensitivity was of great diagnostic significance for the detection of these types of changes in the uterine cervix. On the basis of high predictive values it can be said that in patients with bcl-2 overexpression there is a great possibility that they have premalignant or malignant changes in the uterine cervix. Co-overexpression of bcl-2 and c-myc oncogenes was found only in patients with PVU invasive carcinoma (6/26-23.0%). Statistically significant difference was not found in the frequency of co-overexpression in patients with PVU invasive carcinoma in relation to the control group (Fisher's test; P=0.064). The method's sensitivity of determining these oncogenes with the aim of detecting PVU invasive carcinoma was 23%, while specificity was 72.2%. On the basis of high predictive values (100%), speaking in statistical terms, it can be concluded that all patients with co-overexpression of bcl-2 and c-myc oncogenes will have PVU invasive carcinoma. We confirmed in our research that co-overexpression of bcl-2 and c-myc oncogenes was increased only in PVU invasive carcinoma. However, a more extensive series of samples and additional tests are required to establish the prognostic significance of bcl-2 and c-myc co-overexpression in cervical carcinogenesis

Evaluation of tolerance to lentiviral LV-RPE65 gene therapy vector after subretinal delivery in non-human primates.

Several approaches have been developed for gene therapy in RPE65-related Leber congenital amaurosis. To date, strategies that have reached the clinical stages rely on adeno-associated viral vectors and two of them documented limited long-term effect. We have developed a lentiviral-based strategy of RPE65 gene transfer that efficiently restored protein expression and cone function in RPE65-deficient mice. In this study, we evaluated the ocular and systemic tolerances of this lentiviral-based therapy (LV-RPE65) on healthy nonhuman primates (NHPs), without adjuvant systemic anti-inflammatory prophylaxis. For the first time, we describe the early kinetics of retinal detachment at 2, 4, and 7 days after subretinal injection using multimodal imaging in 5 NHPs. We revealed prolonged reattachment times in LV-RPE65-injected eyes compared to vehicle-injected eyes. Low- (n = 2) and high-dose (n = 2) LV-RPE65-injected eyes presented a reduction of the outer nuclear and photoreceptor outer segment layer thickness in the macula, that was more pronounced than in vehicle-injected eyes (n = 4). All LV-RPE65-injected eyes showed an initial perivascular reaction that resolved spontaneously within 14 days. Despite foveal structural changes, full-field electroretinography indicated that the overall retinal function was preserved over time and immunohistochemistry identified no difference in glial, microglial, or leucocyte ocular activation between low-dose, high-dose, and vehicle-injected eyes. Moreover, LV-RPE65-injected animals did not show signs of vector shedding or extraocular targeting, confirming the safe ocular restriction of the vector. Our results evidence a limited ocular tolerance to LV-RPE65 after subretinal injection without adjuvant anti-inflammatory prophylaxis, with complications linked to this route of administration necessitating to block this transient inflammatory event

Galaxies behind the Galactic plane: First results and perspectives from the VVV Survey

Vista Variables in The Via Lactea (VVV) is an ESO variability survey that is performing observations in near infrared bands (ZYJHKs) towards the Galactic bulge and part of the disk with the completeness limits at least 3 mag deeper than 2MASS. In the present work, we searched in the VVV survey data for background galaxies near the Galactic plane using ZYJHKs photometry that covers 1.636 square degrees. We identified 204 new galaxy candidates by analyzing colors, sizes, and visual inspection of multi-band (ZYJHKs) images. The galaxy candidates colors were also compared with the predicted ones by star counts models considering a more realistic extinction model at the same completeness limits observed by VVV. A comparison of the galaxy candidates with the expected one by Milennium simulations is also presented. Our results increase the number density of known galaxies behind the Milky Way by more than one order of magnitude. A catalog with galaxy properties including ellipticity, Petrosian radii and ZYJHKs magnitudes is provided, as well as comparisons of the results with other surveys of galaxies towards Galactic plane.Comment: 27 pages, 10 figures, 2 tables; in press at The Astronomical Journa

The core-collapse rate from the Supernova Legacy Survey

We use three years of data from the Supernova Legacy Survey (SNLS) to study the general properties of core-collapse and type Ia supernovae. This is the first such study using the "rolling search" technique which guarantees well-sampled SNLS light curves and good efficiency for supernovae brighter than i'~24. Using host photometric redshifts, we measure the supernova absolute magnitude distribution down to luminosities 4.5 mag fainter than normal SNIa. Using spectroscopy and light-curve fitting to discriminate against SNIa, we find a sample of 117 core-collapse supernova candidates with redshifts z < 0.4 (median redshift of 0.29) and measure their rate to be larger than the type Ia supernova rate by a factor 4.5±0.8(stat.)±0.6 (sys.). This corresponds to a core-collapse rate at z = 0.3 of [ 1.42±0.3(stat.)±0.3(sys.)] ×10-4 yr-1(h_70-1 Mpc)-3

Diversity of supernovae Ia determined using equivalent widths of Si II 4000

Spectroscopic and photometric properties of low and high-z supernovae Ia (SNe Ia) have been analyzed in order to achieve a better understanding of their diversity and to identify possible SN Ia sub-types. We use wavelet transformed spectra in which one can easily measure spectral features. We investigate the \ion{Si}{II} 4000 equivalent width (EW_w\lbrace\ion{Si}{II}\rbrace). The ability and, especially, the ease in extending the method to SNe at high-$z$ is demonstrated. We applied the method to 110 SNe Ia and found correlations between EW_w\lbrace\ion{Si}{II}\rbrace and parameters related to the light-curve shape for 88 supernovae with available photometry. No evidence for evolution of EW_w\lbrace\ion{Si}{II}\rbrace with redshift is seen. Three sub-classes of SNe Ia were confirmed using an independent cluster analysis with only light-curve shape, colour, and EW_w\lbrace\ion{Si}{II}\rbrace. SNe from high-$z$ samples seem to follow a similar grouping to nearby objects. The EW_w\lbrace\ion{Si}{II}\rbrace value measured on a single spectrum may point towards SN Ia sub-classification, avoiding the need for expansion velocity gradient calculations.Comment: 12 pages, 5 figure

The Supernova Type Ia Rate Evolution with SNLS

We present a progress report on a project to derive the evolution of the volumetric supernova Type Ia rate from the Supernova Legacy Survey. Our preliminary estimate of the rate evolution divides the sample from Neill et al. into two redshift bins: 0.2 < z < 0.4, and 0.4 < z < 0.6. We extend this by adding a bin from the sample analyzed in Sullivan et al. in the range 0.6 < z < 0.75 from the same time period. We compare the derived trend with previously published rates and a supernova Type Ia production model having two components: one component associated closely with star formation and an additional component associated with host galaxy mass. Our observed trend is consistent with this model, which predicts a rising SN Ia rate out to at least z = 2

The Type Ia Supernova Rate at z ~0.5 from the Supernova Legacy Survey

We present a measurement of the distant Type Ia supernova rate derived from the first two years of the Canada -- France -- Hawaii Telescope Supernova Legacy Survey. We observed four one-square degree fields with a typical temporal frequency of ~ 4 observer-frame days over time spans of from 158 to 211 days per season for each field, with breaks during full moon. We used 8-10 meter-class telescopes for spectroscopic followup to confirm our candidates and determine their redshifts. Our starting sample consists of 73 spectroscopically verified Type Ia supernovae in the redshift range 0.2 < z < 0.6. We derive a volumetric SN Ia rate of r_V(=0.47) = 0.42^{+0.13}_{-0.09} (systematic) +- 0.06 (statistical) X 10^-4 yr^-1 Mpc^3, assuming h = 0.7, Omega_m = 0.3 and a flat cosmology. Using recently published galaxy luminosity functions derived in our redshift range, we derive a SN Ia rate per unit luminosity of r_L(=0.47) = 0.154^{+0.048}_{-0.033} (systematic) ^{+0.039}_{-0.031} (statistical) SNu. Using our rate alone, we place an upper limit on the component of SN Ia production that tracks the cosmic star formation history of 1 SN Ia per 10^3 M_sun of stars formed. Our rate and other rates from surveys using spectroscopic sample confirmation display only a modest evolution out to z=0.55.Comment: 71 pages, 12 figures, accepted for publication in AJ, fixed typos in Eq 3 and

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

Suboptimal maternal nutrition, during early fetal liver development, promotes lipid accumulation in the liver of obese offspring

Maternal nutrition during the period of early organ development can modulate the offspring's ability to metabolise excess fat as young adults when exposed to an obesogenic environment. This study examined the hypothesis that exposing offspring to nutrient restriction coincident with early hepatogenesis would result in endocrine and metabolic adaptations that subsequently lead to increased ectopic lipid accumulation within the liver. Pregnant sheep were fed either 50 or 100% of total metabolisable energy requirements from 30 to 80 days gestation and 100% thereafter. At weaning, offspring were made obese, and at ∼1 year of age livers were sampled. Lipid infiltration and molecular indices of gluconeogenesis, lipid metabolism and mitochondrial function were measured. Although hepatic triglyceride accumulation was not affected by obesity per se, it was nearly doubled in obese offspring born to nutrient-restricted mothers. This adaptation was accompanied by elevated gene expression for peroxisome proliferator-activated receptor γ (PPARG) and its co-activator PGC1α, which may be indicative of changes in the rate of hepatic fatty acid oxidation. In contrast, maternal diet had no influence on the stimulatory effect of obesity on gene expression for a range of proteins involved in glucose metabolism and energy balance including glucokinase, glucocorticoid receptors and uncoupling protein 2. Similarly, although gene expressions for the insulin and IGF1 receptors were suppressed by obesity they were not influenced by the prenatal nutritional environment. In conclusion, excess hepatic lipid accumulation with juvenile obesity is promoted by suboptimal nutrition coincident with early development of the fetal liver