Vertebrate DNA damage tolerance requires the C-terminus but not BRCT or transferase domains of REV1

REV1 is central to the DNA damage response of eukaryotes through an as yet poorly understood role in translesion synthesis. REV1 is a member of the Y-type DNA polymerase family and is capable of in vitro deoxycytidyl transferase activity opposite a range of damaged bases. However, non-catalytic roles for REV1 have been suggested by the Saccharomyces cerevisiae rev1-1 mutant, which carries a point mutation in the N-terminal BRCT domain, and the recently demonstrated ability of the mammalian protein to interact with each of the other translesion polymerases via its extreme C-terminus. Here, we show that a region adjacent to this polymerase interacting domain mediates an interaction with PCNA. These C-terminal domains of REV1 are necessary, although not sufficient, for effective tolerance of DNA damage in the avian cell line DT40, while the BRCT domain and transferase activity are not directly required. Together these data provide strong support for REV1 playing an important non-catalytic role in coordinating translesion synthesis. Further, unlike in budding yeast, rad18 is not epistatic to rev1 for DNA damage tolerance suggesting that REV1 and RAD18 play largely independent roles in the control of vertebrate translesion synthesis

PrimPol is required for replicative tolerance of G quadruplexes in vertebrate cells

G quadruplexes (G4s) can present potent blocks to DNA replication. Accurate and timely replication of G4s in vertebrates requires multiple specialized DNA helicases and polymerases to prevent genetic and epigenetic instability. Here we report that PrimPol, a recently described primase-polymerase (PrimPol), plays a crucial role in the bypass of leading strand G4 structures. While PrimPol is unable to directly replicate G4s, it can bind and reprime downstream of these structures. Disruption of either the catalytic activity or zinc-finger of PrimPol results in extreme G4-dependent epigenetic instability at the BU-1 locus in avian DT40 cells, indicative of extensive uncoupling of the replicative helicase and polymerase. Together, these observations implicate PrimPol in promoting restart of DNA synthesis downstream of, but closely coupled to, G4 replication impediments

UV Imaging Polarimetry of the peculiar Seyfert 2 galaxy Mrk 477

We present the results of UV imaging polarimetry of the Seyfert 2 galaxy Mrk 477 taken by the Faint Object Camera onboard the Hubble Space Telescope (HST). From a previous HST UV image (lambda ~ 2180A), Mrk 477 has been known to have a pointlike bright UV hotspot in the central region, peculiar among nearby Seyfert 2 galaxies. There are also claims of UV/optical variability, unusual for a Seyfert 2 galaxy. Our data show that there is an off-nuclear scattering region ~ 0."6 (~ 500 pc) NE from the hotspot. The data, after the subtraction of the instrumental effect due to this bright hotspot region, might indicate that the scattered light is also detected in the central 0."2 radius region and is extended to a very wide angle. The hotspot location is consistent with the symmetry center of the PA pattern, which represents the location of the hidden nucleus, but our data do not provide a strong upper limit to the distance between the symmetry center and the hotspot. We have obtained high spatial resolution color map of the continuum which shows that the nuclear spiral arm of 0."4 scale (~ 300pc) is significantly bluer than the off-nuclear mirror and the hotspot region. The nature of the hotspot is briefly discussed.Comment: To appear in Ap

UV Imaging Polarimetry of the Seyfert 2 Galaxy Mrk 3

We present UV imaging polarimetry data of the Seyfert 2 galaxy Mrk 3 taken by the Hubble Space Telescope. The polarized flux is found to be extended to ~1 kpc from the nucleus, and the position angles of polarization are centrosymmetric, confirming that the polarization is caused by scattering. We determine the location of the hidden nucleus as the center of this centrosymmetric pattern. From the polarization images taken in two broad bands, we have obtained the color distribution of the polarized flux. Some regions have blue polarized flux, consistent with optically-thin dust scattering, but some bright knots have a color similar to that of Seyfert 1 nucleus. Also, the recent Chandra X-ray observation suggests that the ratio of scattered UV flux to scattered X-ray flux is rather similar to the intrinsic UV/X-ray ratio in a Seyfert 1 nucleus, if the observed extended X-ray continuum is scattered light. While the scattered X-ray would be essentially from electron scattering, the UV slope and UV/X-ray ratio both being similar to Seyfert 1's would lead to two possibilities as to the nature of the UV scatterers. One is that the UV may also be scattered by electrons, in which case the scattering gas is somehow dust-free. The other is that the UV is scattered by dust grains, but the wavelength-independent UV scattering with low efficiency indicated by the UV slope and UV/X-ray ratio would suggest that the grains reside in UV-opaque clouds, or the dust might be mainly composed of large grains and lacks small-grain population.Comment: 15 pages, 8 figures (plus 2 color versions of grayscale figures), To appear in ApJ; minor corrections for the proofs of the manuscrip

The 2011 Outburst of Recurrent Nova T Pyx: X-ray Observations Expose the White Dwarf Mass and Ejection Dynamics

The recurrent nova T Pyx underwent its sixth historical outburst in 2011, and became the subject of an intensive multi-wavelength observational campaign. We analyze data from the Swift and Suzaku satellites to produce a detailed X-ray light curve augmented by epochs of spectral information. X-ray observations yield mostly non-detections in the first four months of outburst, but both a super-soft and hard X-ray component rise rapidly after Day 115. The super-soft X-ray component, attributable to the photosphere of the nuclear-burning white dwarf, is relatively cool (~45 eV) and implies that the white dwarf in T Pyx is significantly below the Chandrasekhar mass (~1 M_sun). The late turn-on time of the super-soft component yields a large nova ejecta mass (>~10^-5 M_sun), consistent with estimates at other wavelengths. The hard X-ray component is well fit by a ~1 keV thermal plasma, and is attributed to shocks internal to the 2011 nova ejecta. The presence of a strong oxygen line in this thermal plasma on Day 194 requires a significantly super-solar abundance of oxygen and implies that the ejecta are polluted by white dwarf material. The X-ray light curve can be explained by a dual-phase ejection, with a significant delay between the first and second ejection phases, and the second ejection finally released two months after outburst. A delayed ejection is consistent with optical and radio observations of T Pyx, but the physical mechanism producing such a delay remains a mystery.Comment: Re-submitted to ApJ after revision

How Food & Fitness Community Partnerships Successfully Engaged Youth

Authentic youth engagement was a central component of the Food & Fitness (F&F) Initiative, a 9-year community-based intervention, whose goal was to ensure that all children have equitable access to healthy food and built environments that promote safe physical activity. The youth engagement component focused on strategies and structures that would support a model framework for youth involved in F&F community partnerships. These strategies empowered youth by providing the leadership and technical skills needed in collaborative efforts to sustain change in communities with inequities, where structural racism and inequities result in poor health outcomes for children. This article describes the models that the diverse urban and rural communities across the United States employed to successfully engage youth in the vision and work of F&F and discusses overall lessons learned, challenges, and best practices/recommendations for effectively engaging youth in community-determined change

Development of a Community-Based Rehabilitation Intervention for People with Schizophrenia in Ethiopia.

BACKGROUND: Community-based rehabilitation (CBR) is a multi-sectoral strategy to improve the functioning and quality of life of people with disabilities. The RISE (Rehabilitation Intervention for people with Schizophrenia in Ethiopia) trial will evaluate the effectiveness of CBR for people with schizophrenia in Ethiopia. Nevertheless, the components of CBR that are both feasible and likely to prove effective in low and middle-income countries such as Ethiopia are unclear. METHODS: In this study intervention development work was undertaken to design a CBR intervention that is acceptable and feasible in the local context. The development work consisted of five phases. 1: Identify potential components of CBR for schizophrenia, 2: Situational analysis, 3: Determine feasibility of CBR (Theory of Change workshops with experts and local stakeholders), 4: Determine acceptability of CBR (16 in-depth interviews and five focus group discussions with people with schizophrenia, caregivers, health workers and community leaders) and 5: Synthesise results to finalise intervention. A Theory of Change map was constructed showing the causal pathway for how we expect CBR to achieve its impact. RESULTS: People with schizophrenia in rural Ethiopia experience family conflict, difficulty participating in work and community life, and stigma. Stakeholders perceived CBR to be acceptable and useful to address these problems. The focus of CBR will be on the individual developing the skills and confidence to perform their previous or desired roles and activities. To ensure feasibility, non-health professionals will be trained to deliver CBR and provide supervision, rather than mental health specialists. Novel components of CBR for schizophrenia included family intervention and dealing with distressing symptoms. Microfinance was excluded due to concerns about stress and exploitation. Community mobilisation was viewed as essential to ensure the effectiveness and sustainability of CBR. CONCLUSION: Extensive formative research using a variety of methods has enabled the design of a culturally appropriate CBR intervention for people with schizophrenia that is acceptable and feasible

Provision of preventive health care in systemic lupus erythematosus: data from a large observational cohort study

IntroductionCancer and infections are leading causes of mortality in systemic lupus erythematosus (SLE) after diseases of the circulatory system, and therefore preventing these complications is important. In this study, we examined two categories of preventive services in SLE: cancer surveillance (cervical, breast, and colon) and immunizations (influenza and pneumococcal). We compared the receipt of these services in SLE to the general population, and identified subgroups of patients who were less likely to receive these services.MethodsWe compared preventive services reported by insured women with SLE enrolled in the University of California, San Francisco Lupus Outcomes Study (n=685) to two representative samples derived from a statewide health interview survey, a general population sample (n=18,013) and a sample with non-rheumatic chronic conditions (n=4,515). In addition, using data from the cohort in both men and women (n=742), we applied multivariate regression analyses to determine whether characteristics of individuals (for example, sociodemographic and disease factors), health systems (for example, number of visits, involvement of generalists or rheumatologists in care, type of health insurance) or neighborhoods (neighborhood poverty) influenced the receipt of services.ResultsThe receipt of preventive care in SLE was similar to both comparison samples. For cancer surveillance, 70% of eligible respondents reported receipt of cervical cancer screening and mammography, and 62% reported colon cancer screening. For immunizations, 59% of eligible respondents reported influenza immunization, and 60% reported pneumococcal immunization. In multivariate regression analyses, several factors were associated with a lower likelihood of receiving preventive services, including younger age and lower educational attainment. We did not observe any effects by neighborhood poverty. A higher number of physician visits and involvement of generalist providers in care was associated with a higher likelihood of receiving most services.ConclusionsAlthough receipt of cancer screening procedures and immunizations in our cohort was comparable to the general population, we observed significant variability by sociodemographic factors such as age and educational attainment. Further research is needed to identify the physician, patient or health system factors contributing to this observed variation in order to develop effective quality improvement interventions

Peak Oil:Die Herausforderung lokaler Erdölabhängigkeit am Beispiel Münster

Das Erdölzeitalter neigt sich dem Ende zu – daran ändern auch Schieferöle, Agrartreibstoffe oder Verfahren wie das Fracking langfristig nichts. Einer Gruppe von Studierenden an der Uni Münster ging die wissenschaftliche, politische und gesellschaftliche Beschäftigung mit dieser Herausforderung zu langsam. Aus diesem Grund initiierte sie 2012 eigenständig ein interdisziplinäres Peak-Oil-Seminar und begleitete Studierende dabei, in gesellschaftsrelevanten Sektoren der Energieversorgung, des Transports, der lokalen Wirtschaft, der Ernährung, der Gesundheit und der privaten Haushalte eigene Fragestellungen zu entwickeln und diesen nachzugehen. Das Ergebnis ist ein Bericht, der am Beispiel Münster die Brisanz und Aktualität knapper werdender Ressourcen herausstreicht, der die Wichtigkeit der lokalen, vorausschauenden und freiwillig-kreativen Verringerung der Öl-Abhängigkeit hervorhebt und der nicht zuletzt eine Lanze bricht für Formate transformativen und offenen Forschens und Handelns. <br