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

Systematic variations of central mass density slopes in early-type galaxies

We study the total density distribution in the central regions (≳1 effective radius, Re) of earlytype galaxies (ETGs), using data from SPIDER and ATLAS3D. Our analysis extends the range of galaxy stellar mass (M*) probed by gravitational lensing, down to ~1010M. We model each galaxy with two components (dark matter halo + stars), exploring different assumptions for the dark matter halo profile (i.e. NFW, NFW-contracted, and Burkert profiles), and leaving stellar mass-to-light (M*/L) ratios as free fitting parameters to the data. For all plausible halo models, the best-fitting M*/L, normalized to that for a Chabrier initial mass function, increases systematically with galaxy size and mass. For anNFWprofile, the slope of the total mass profile is non-universal, independently of several ingredients in the modelling (e.g. halo contraction, anisotropy, and rotation velocity in ETGs). For the most massive (M* ~ 1011.5M) or largest (Re ~ 15 kpc) ETGs, the profile is isothermal in the central regions (~Re/2), while for the low-mass (M* ~ 1010.2M) or smallest (Re ~ 0.5 kpc) systems, the profile is steeper than isothermal, with slopes similar to those for a constant-M/L profile. For a steeper concentration- mass relation than that expected from simulations, the correlation of density slope with galaxy mass tends to flatten, while correlations with Re and velocity dispersions are more robust. Our results clearly point to a 'non-homology' in the total mass distribution of ETGs, which simulations of galaxy formation suggest may be related to a varying role of dissipation with galaxy mass. 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society

Arrest in ciliated cell expansion on the bronchial lining of adult rats caused by chronic exposure to industrial noise

Workers chronically exposed to high-intensity/low-frequency noise at textile plants show increased frequency of respiratory infections. This phenomenon prompted the herein investigation on the cytology of the bronchial epithelium of Wistar rats submitted to textile noise. Workplace noise from a cotton-mill room of a textile factory was recorded and reproduced in a sound-insulated animal room. The Wistar rats were submitted to a weekly schedule of noise treatment that was similar to that of the textile workers (8 h/day, 5 days/week). Scanning electron microscopy (SEM) was used to compare the fine morphology of the inner surface of the bronchi in noise-exposed and control rats. SEM quantitative cytology revealed that exposure to noise for 5-7 months caused inhibition in the natural expansion of the area occupied by ciliated cells on the bronchial epithelium as adult rats grow older. This difference between noise-exposed and age-matched control rats was statistically significant (P<0.05) and documents that the cytology of the rat bronchial epithelium is mildly altered by noise exposure. The decrease in the area of bronchial cilia may impair the mucociliar clearance of the respiratory airways and, thus, increase vulnerability to respiratory infection

Roadmaps to Utopia: Tales of the Smart City

Notions of the Smart City are pervasive in urban development discourses. Various frameworks for the development of smart cities, often conceptualized as roadmaps, make a number of implicit claims about how smart city projects proceed but the legitimacy of those claims is unclear. This paper begins to address this gap in knowledge. We explore the development of a smart transport application, MotionMap, in the context of a £16M smart city programme taking place in Milton Keynes, UK. We examine how the idealized smart city narrative was locally inflected, and discuss the differences between the narrative and the processes and outcomes observed in Milton Keynes. The research shows that the vision of data-driven efficiency outlined in the roadmaps is not universally compelling, and that different approaches to the sensing and optimization of urban flows have potential for empowering or disempowering different actors. Roadmaps tend to emphasize the importance of delivering quick practical results. However, the benefits observed in Milton Keynes did not come from quick technical fixes but from a smart city narrative that reinforced existing city branding, mobilizing a growing network of actors towards the development of a smart region. Further research is needed to investigate this and other smart city developments, the significance of different smart city narratives, and how power relationships are reinforced and constructed through them

TumorBoost: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays

<p>Abstract</p> <p>Background</p> <p>High-throughput genotyping microarrays assess both total DNA copy number and allelic composition, which makes them a tool of choice for copy number studies in cancer, including total copy number and loss of heterozygosity (LOH) analyses. Even after state of the art preprocessing methods, allelic signal estimates from genotyping arrays still suffer from systematic effects that make them difficult to use effectively for such downstream analyses.</p> <p>Results</p> <p>We propose a method, TumorBoost, for normalizing allelic estimates of one tumor sample based on estimates from a single matched normal. The method applies to any paired tumor-normal estimates from any microarray-based technology, combined with any preprocessing method. We demonstrate that it increases the signal-to-noise ratio of allelic signals, making it significantly easier to detect allelic imbalances.</p> <p>Conclusions</p> <p>TumorBoost increases the power to detect somatic copy-number events (including copy-neutral LOH) in the tumor from allelic signals of Affymetrix or Illumina origin. We also conclude that high-precision allelic estimates can be obtained from a single pair of tumor-normal hybridizations, if TumorBoost is combined with single-array preprocessing methods such as (allele-specific) CRMA v2 for Affymetrix or BeadStudio's (proprietary) XY-normalization method for Illumina. A bounded-memory implementation is available in the open-source and cross-platform R package <it>aroma.cn</it>, which is part of the Aroma Project (<url>http://www.aroma-project.org/</url>).</p

Tribological behavior of 316L stainless steel reinforced with CuCoBe + diamond composites by laser sintering and hot pressing: a comparative statistical study

The aim of this work was to perform a statistical analysis in order to assess how the tribological properties of a laser textured 316L stainless steel reinforced with CuCoBe - diamond composites are affected by diamond particles size, type of technology (laser sintering and hot pressing) and time of tribological test. The analysis started with the description of all response variables. Then, by using IBM® SPSS software, the Friedman’s test was used to compare how the coefficient of friction varied among samples in five-time points. From this test, results showed that there was no statistically significant difference in the coefficient of friction mean values over the selected time points. Then, the two-samples Kolmogorov-Smirnov (K-S) test was used to test the effect of the diamond particles size and the type of technology on the mean of the coefficient of friction over time. The results showed that, for both sintering techniques, the size of the diamond particles significantly affected the values of the coefficient of friction, whereas no statistical differences were found between the tested sintering techniques. Also, the two-way ANOVA test was used to evaluate how these factors influence the specific wear rate, which conducted to the same conclusions drawn for the previous test. The main conclusion was that the coefficient of friction and the specific wear rate were statistically affected by the diamond particles size, but not by the sintering techniques used in this work.This work was supported by FCT national funds, under the national support to R&D units grant, through the reference projects UIDB/04436/2020 and UIDP/04436/2020. Additionally, this work was supported by FCT with the reference projects UIDB/00319/2020 and PTDC/CTM-COM/30416/2017