Animal modelling for inherited central vision loss.

Disease-causing variants of a large number of genes trigger inherited retinal degeneration leading to photoreceptor loss. Because cones are essential for daylight and central vision such as reading, mobility, and face recognition, this review focuses on a variety of animal models for cone diseases. The pertinence of using these models to reveal genotype/phenotype correlations and to evaluate new therapeutic strategies is discussed. Interestingly, several large animal models recapitulate human diseases and can serve as a strong base from which to study the biology of disease and to assess the scale-up of new therapies. Examples of innovative approaches will be presented such as lentiviral-based transgenesis in pigs and adeno-associated virus (AAV)-gene transfer into the monkey eye to investigate the neural circuitry plasticity of the visual system. The models reported herein permit the exploration of common mechanisms that exist between different species and the identification and highlighting of pathways that may be specific to primates, including humans

Catalog of Radio Galaxies with z>0.3. I:Construction of the Sample

The procedure of the construction of a sample of distant ($z>0.3$) radio galaxies using NED, SDSS, and CATS databases for further application in statistical tests is described. The sample is assumed to be cleaned from objects with quasar properties. Primary statistical analysis of the list is performed and the regression dependence of the spectral index on redshift is found.Comment: 9 pages, 6 figures, 2 table

Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

The VIMOS VLT Deep Survey: the group catalogue

[Abridged] We present a homogeneous and complete catalogue of optical groups identified in the purely flux limited (17.5<=I<=24.0) VIMOS-VLT Deep Survey (VVDS). We use mock catalogues extracted from the MILLENNIUM simulation, to correct for potential systematics that might affect the overall distribution as well as the individual properties of the identified systems. Simulated samples allow us to forecast the number and properties of groups that can be potentially found in a survey with VVDS-like selection functions. We use them to correct for the expected incompleteness and also to asses how well galaxy redshifts trace the line-of-sight velocity dispersion of the underlying mass overdensity. In particular, we train on these mock catalogues the adopted group-finding technique (the Voronoi-Delaunay Method, VDM). The goal is to fine-tune its free parameters, recover in a robust and unbiased way the redshift and velocity dispersion distributions of groups and maximize the level of completeness (C) and purity (P) of the group catalogue. We identify 318 VVDS groups with at least 2 members within 0.2<=z<=1.0, among which 144 (/30) with at least 3 (/5) members. The sample has globally C=60% and P=50%. Nearly 45% of the groups with at least 3 members are still recovered if we run the algorithm with a parameter set which maximizes P (75%). We exploit the group sample to study the redshift evolution of the fraction f_b of blue galaxies (U-B<=1) within 0.2<=z<=1. We find that f_b is significantly lower in groups than in the whole ensemble of galaxies irrespectively of their environment. These quantities increase with redshift, with f_b in groups showing a marginally significant steeper increase. We also confirm that, at any explored redshift, f_b decreases for increasing group richness, and we extend towards fainter luminosities the magnitude range over which this result holds.Comment: Submitted to A&A, revised version after referee comments, Table 5 adde

Gene–Environment Interactions at Nucleotide Resolution

Interactions among genes and the environment are a common source of phenotypic variation. To characterize the interplay between genetics and the environment at single nucleotide resolution, we quantified the genetic and environmental interactions of four quantitative trait nucleotides (QTN) that govern yeast sporulation efficiency. We first constructed a panel of strains that together carry all 32 possible combinations of the 4 QTN genotypes in 2 distinct genetic backgrounds. We then measured the sporulation efficiencies of these 32 strains across 8 controlled environments. This dataset shows that variation in sporulation efficiency is shaped largely by genetic and environmental interactions. We find clear examples of QTN:environment, QTN: background, and environment:background interactions. However, we find no QTN:QTN interactions that occur consistently across the entire dataset. Instead, interactions between QTN only occur under specific combinations of environment and genetic background. Thus, what might appear to be a QTN:QTN interaction in one background and environment becomes a more complex QTN:QTN:environment:background interaction when we consider the entire dataset as a whole. As a result, the phenotypic impact of a set of QTN alleles cannot be predicted from genotype alone. Our results instead demonstrate that the effects of QTN and their interactions are inextricably linked both to genetic background and to environmental variation

High-order 3D Voronoi tessellation for identifying Isolated galaxies, Pairs and Triplets

Geometric method based on the high-order 3D Voronoi tessellation is proposed for identifying the single galaxies, pairs and triplets. This approach allows to select small galaxy groups and isolated galaxies in different environment and find the isolated systems. The volume-limited sample of galaxies from the SDSS DR5 spectroscopic survey was used. We conclude that in such small groups as pairs and triplets the segregation by luminosity is clearly observed: galaxies in the isolated pairs and triplets are on average two times more luminous than isolated galaxies. We consider the dark matter content in different systems. The median values of mass-to-luminosity ratio are 12 M_sol/L_sol for the isolated pairs and 44 M_sol/L_sol for the isolated triplets; 7 (8) M_sol/L_sol for the most compact pairs (triplets). We found also that systems in the denser environment have greater rms velocity and mass-to-luminosity ratio.Comment: 11 pages, 7 figures, Accepted 2008 October 25 in MNRA

Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair

Eukaryotic cells possess a universal repair machinery that ensures rapid resealing of plasma membrane disruptions. Before resealing, the torn membrane is submitted to considerable tension, which functions to expand the disruption. Here we show that annexin-A5 (AnxA5), a protein that self-assembles into two-dimensional (2D) arrays on membranes upon Ca2+ activation, promotes membrane repair. Compared with wild-type mouse perivascular cells, AnxA5-null cells exhibit a severe membrane repair defect. Membrane repair in AnxA5-null cells is rescued by addition of AnxA5, which binds exclusively to disrupted membrane areas. In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair. We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca2+, AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing

Comparison of the VIMOS-VLT Deep Survey with the Munich semi-analytical model. II. The colour-density relation up to z=1.5

[Abridged] We perform on galaxy mock catalogues the same colour-density analysis made by Cucciati et al. (2006) on a 5 Mpc/h scale using the VVDS-Deep survey, and compare the results from mocks with observed data. We use mocks with the same flux limits (I=24) as the VVDS (CMOCKS), built using the semi- analytic model by De Lucia & Blaizot (2007) applied to the Millennium Simulation. From CMOCKS, we extracted samples of galaxies mimicking the VVDS observational strategy (OMOCKS). We computed the B-band Luminosity Function LF and the colour-density relation (CDR) in the mocks. We find that the LF in mocks roughly agrees with the observed LF, but at z<0.8 the faint-end slope of the model LF is steeper than the VVDS one. Computing the LF for early and late type galaxies, we show that mocks have an excess of faint early-type and of bright late-type galaxies with respect to data. We find that the CDR in OMOCKS is in excellent agreement with the one in CMOCKS. At z~0.7, the CDR in mocks agrees with the VVDS one (red galaxies reside mainly in high densities). Yet, the strength of the CDR in mocks does not vary within 0.2<z<1.5, while the observed relation flattens with increasing z and possibly inverts at z=1.3. We argue that the lack of evolution in the CDR in mocks is not due only to inaccurate prescriptions for satellite galaxies, but that also the treatment of central galaxies has to be revised. The reversal of the CDR can be explained by wet mergers between young galaxies, producing a starburst event. This should be seen on group scales. A residual of this is found in observations at z=1.5 on larger scales, but not in the mocks, suggesting that the treatment of physical processes affecting satellites and central galaxies in models should be revised.Comment: 15 pages, 12 figures, accepted for publication in A&

High specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG positive Ewing sarcoma

Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available

Tracing the cosmic growth of supermassive black holes to z~3 with Herschel

We study a sample of Herschel selected galaxies within the Great Observatories Origins Deep Survey-South and the Cosmic Evolution Survey fields in the framework of the Photodetector Array Camera and Spectrometer (PACS) Evolutionary Probe project. Starting from the rich multiwavelength photometric data sets available in both fields, we perform a broad-band spectral energy distribution decomposition to disentangle the possible active galactic nucleus (AGN) contribution from that related to the host galaxy. We find that 37 per cent of the Herschel-selected sample shows signatures of nuclear activity at the 99 per cent confidence level. The probability of revealing AGN activity increases for bright (L 1−1000 > 10 11 L ? ) star-forming galaxies at z > 0.3, becoming about 80 per cent for the brightest (L 1−1000 > 10 12 L ? ) Infrared (IR) galaxies at z≥1. Finally, we reconstruct the AGN bolometric luminosity function and the supermassive black hole growth rate across cosmic time up to z ∼ 3 from a far-IR perspective. This work shows general agreement with most of the panchromatic estimates from the literature, with the global black hole growth peaking at z ∼ 2 and reproducing the observed local black hole mass density with consistent values of the radiative efficiency Erad (∼0.07)