1,187 research outputs found

    Mechanisms of transcriptional stalling and mutagenesis at DNA lesions.

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    Hydrogen peroxide is a neuronal alarmin that triggers specific RNAs, local translation of Annexin A2, and cytoskeletal remodeling in Schwann cells

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    Schwann cells are key players in neuro-regeneration: They sense "alarm" signals released by degenerating nerve terminals and differentiate toward a proregenerative phenotype, with phagocytosis of nerve debris and nerve guidance. At the murine neuromuscular junction, hydrogen peroxide (H2O2) is a key signal of Schwann cells' activation in response to a variety of nerve injuries. Here we report that Schwann cells exposed to low doses of H2O2 rewire the expression of several RNAs at both transcriptional and translational levels. Among the genes positively regulated at both levels, we identified an enriched cluster involved in cytoskeleton remodeling and cell migration, with the Annexin (Anxa) proteins being the most represented family. We show that both Annexin A2 (Anxa2) transcript and protein accumulate at the tips of long pseudopods that Schwann cells extend upon H2O2 exposure. Interestingly, Schwann cells reply to this signal and to nerve injury by locally translating Anxa2 in pseudopods, and undergo an extensive cytoskeleton remodeling. Our results show that, similarly to neurons, Schwann cells take advantage of local protein synthesis to change shape and move toward damaged axonal terminals to facilitate axonal regeneration

    Groups of Galaxies in AEGIS: The 200 ksec Chandra Extended X-ray Source catalogue

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    We present the discovery of seven X-ray emitting groups of galaxies selected as extended X-ray sources in the 200 ksec Chandra coverage of the All-wavelength Extended Groth Strip International Survey (AEGIS). In addition, we report on AGN activity associated to these systems. Using the DEEP2 Galaxy Redshift Survey coverage, we identify optical counterparts and determine velocity dispersions. In particular, we find three massive high-redshift groups at z>0.7, one of which is at z=1.13, the first X-ray detections of spectroscopically selected DEEP2 groups. We also present a first look at the the L_X-T, L_X-sigma, and sigma-T scaling relations for high-redshift massive groups. We find that the properties of these X-ray selected systems agree well with the scaling relations of similar systems at low redshift, although there are X-ray undetected groups in the DEEP2 catalogue with similar velocity dispersions. The other three X-ray groups with identified redshifts are associated with lower mass groups at z~0.07 and together form part of a large structure or "supergroup" in the southern portion of the AEGIS field. All of the low-redshift systems are centred on massive elliptical galaxies, and all of the high-redshift groups have likely central galaxies or galaxy pairs. All of the central group galaxies host X-ray point sources, radio sources, and/or show optical AGN emission. Particularly interesting examples of central AGN activity include a bent-double radio source plus X-ray point source at the center of a group at z=0.74, extended radio and double X-ray point sources associated to the central galaxy in the lowest-redshift group at z=0.066, and a bright green valley galaxy (part of a pair) in the z=1.13 group which shows optical AGN emission lines.Comment: accepted to MNRAS, 15 pages, 11 figures, for version with full resolution figures see http://www.ucolick.org/~tesla/aegis_groups.ps.g

    When Is a Change Significant? The Update Problem of Apps in Medical and Behavioral Research

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    Digital applications (apps) are commonly used across the research ecosystem. While apps are frequently updated in the course of clinical and behavioral research, there is limited guidance as to when an app update should trigger action related to human research participant protections and who should be responsible for monitoring and reviewing these updates. We term this the “update problem” and argue that, while it is the principal investigator\u27s duty to track all relevant updates, the level of involvement and re-review by the institutional review board (IRB) of an approved research protocol should vary depending on whether the update may be classified as minor, not minor, or significant. Minor updates require at most annual notification of the IRB, updates that are not minor require prompt notification of the IRB, and significant updates may require full board re-review or another response. We also suggest how these policies might be implemented

    X-ray selected AGN in groups at redshifts z~1

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    We explore the role of the group environment in the evolution of AGN at the redshift interval 0.7<z<1.4, by combining deep Chandra observations with extensive optical spectroscopy from the All-wavelength Extended Groth strip International Survey (AEGIS). The sample consists of 3902 optical sources and 71 X-ray AGN. Compared to the overall optically selected galaxy population, X-ray AGN are more frequently found in groups at the 99% confidence level. This is partly because AGN are hosted by red luminous galaxies, which are known to reside, on average, in dense environments. Relative to these sources, the excess of X-ray AGN in groups is significant at the 91% level only. Restricting the sample to 0.7<z<0.9 and M_B<-20mag in order to control systematics we find that X-ray AGN represent (4.7\pm1.6) and (4.5\pm1.0)% of the optical galaxy population in groups and in the field respectively. These numbers are consistent with the AGN fraction in low redshift clusters, groups and the field. The results above, although affected by small number statistics, suggest that X-ray AGN are spread over a range of environments, from groups to the field, once the properties of their hosts (e.g. colour, luminosity) are accounted for. There is also tentative evidence, significant at the 98% level, that the field produces more X-ray luminous AGN compared to groups, extending similar results at low redshift to z~1. This trend may be because of either cold gas availability or the nature of the interactions occurring in the denser group environment (i.e. prolonged tidal encounters).Comment: To appear in MNRA

    The expression levels of three raft-associated molecules in cultivated vascular cells are dependent on culture conditions

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    Relaying a signal across the plasma membrane requires functional connections between the partner molecules. Membrane microdomains or lipid rafts provide an environment in which such specific interactions can take place. The integrity of these sites is often taken for granted when signalling pathways are investigated in cell culture. However, it is well known that smooth muscle and endothelial cells undergo cytoskeletal rearrangements during monolayer culturing. Likewise affected - and with potentially important consequences for signalling events - is the organization of the plasma membrane. The expression levels of three raft markers were massively upregulated, and raft-associated 5′-nucleotidase activity increased in conventional monolayer cultures as compared with a spheroidal coculture model, shown to promote the differentiation of endothelial cells. Our data point to a shift of raft components in monolayer cultures and demonstrate potential advantages of the spheroid coculture system for investigation of raft-mediated signalling events in endothelial cell
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