1,587 research outputs found

    Reconstitution of recombination-associated DNA synthesis with human proteins.

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    The repair of DNA breaks by homologous recombination is a high-fidelity process, necessary for the maintenance of genome integrity. Thus, DNA synthesis associated with recombinational repair must be largely error-free. In this report, we show that human DNA polymerase delta (δ) is capable of robust DNA synthesis at RAD51-mediated recombination intermediates dependent on the processivity clamp PCNA. Translesion synthesis polymerase eta (η) also extends these substrates, albeit far less processively. The single-stranded DNA binding protein RPA facilitates recombination-mediated DNA synthesis by increasing the efficiency of primer utilization, preventing polymerase stalling at specific sequence contexts, and overcoming polymerase stalling caused by topological constraint allowing the transition to a migrating D-loop. Our results support a model whereby the high-fidelity replicative DNA polymerase δ performs recombination-associated DNA synthesis, with translesion synthesis polymerases providing a supportive role as in normal replication

    Carbon Accounting by Public and Private Financial Institutions: Can We Be Sure Climate Finance Is Leading to Emissions Reductions?

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    As reporting GHG emissions becomes mandatory in the financial sector, the methods by which emissions are calculated will grow in importance for their impact on the resulting metric. Progress is underway in both the public and private financial sectors to embed emissions accounting standards, but there is still a long way to go to make them universal and harmonized. This report addresses key developments that both multilateral development banks (MDBs)—major actors in public climate finance—and private financial institutions have made toward adopting and harmonizing methodologies for calculating financed emissions

    Prenatal Insecticide Exposures and Birth Weight and Length among an Urban Minority Cohort

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    We reported previously that insecticide exposures were widespread among minority women in New York City during pregnancy and that levels of the organophosphate chlorpyrifos in umbilical cord plasma were inversely associated with birth weight and length. Here we expand analyses to include additional insecticides (the organophosphate diazinon and the carbamate propoxur), a larger sample size (n = 314 mother–newborn pairs), and insecticide measurements in maternal personal air during pregnancy as well as in umbilical cord plasma at delivery. Controlling for potential confounders, we found no association between maternal personal air insecticide levels and birth weight, length, or head circumference. For each log unit increase in cord plasma chlorpyrifos levels, birth weight decreased by 42.6 g [95% confidence interval (CI), −81.8 to −3.8, p = 0.03] and birth length decreased by 0.24 cm (95% CI, −0.47 to −0.01, p = 0.04). Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were also inversely associated with birth weight and length (p < 0.05). Birth weight averaged 186.3 g less (95% CI, −375.2 to −45.5) among newborns with the highest compared with lowest 26% of exposure levels (p = 0.01). Further, the associations between birth weight and length and cord plasma chlorpyrifos and diazinon were highly significant (p ≤ 0.007) among newborns born before the 2000–2001 U.S. Environmental Protection Agency’s regulatory actions to phase out residential use of these insecticides. Among newborns born after January 2001, exposure levels were substantially lower, and no association with fetal growth was apparent (p > 0.8). The propoxur metabolite 2-isopropoxyphenol in cord plasma was inversely associated with birth length, a finding of borderline significance (p = 0.05) after controlling for chlorpyrifos and diazinon. Results indicate that prenatal chlorpyrifos exposures have impaired fetal growth among this minority cohort and that diazinon exposures may have contributed to the effects. Findings support recent regulatory action to phase out residential uses of the insecticides

    From workplace to home environment: spreading of mouse allergens by laboratory animal workers

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    PURPOSE Laboratory animal workers (LAW) working with laboratory mice are exposed to mouse allergens (MA). If MA are spread to home environments, this might increase the risk for allergies in LAW and their families. This study aimed to assess 1. whether spreading of MA from workplace to home environment takes place; 2. which factors increase spreading of MA. METHODS In a cross-sectional study, dust samples were taken on the mattress and seating in homes of LAW (n = 105) and an unexposed comparison group (n = 13). From 89 LAW, additional dust samples were taken from their workplaces. Samples were analysed using Mus m1 ELISA kits detection limit (DL) 0.2~ng mus m1/ml. Sociodemographic data, personal history of allergies and cleaning habits, as well as work-related characteristics (LAW only) were assessed by questionnaire. Latent factors were assessed via factor analysis. Tobit models were fitted to analyse the latent factors' contribution to MA spreading. RESULTS MA concentration on the seating was significantly higher in home environments of LAW (median = 1.28~ng mus m1/m2) than in the comparison group (median < DL, p = 0.019). The highest workplace MA concentration was found on the floor of the scullery (median = 140,000.00~ng mus m1/m2), followed by hair-covering caps (median = 76.02~ng mus m1/m2). Cage and mouse facility cleaning tasks and infrequent changing of bed linen at home were statistically significantly associated with higher MA concentrations at home. CONCLUSIONS Spreading of MA from LAW's workplace to their home environment takes place, especially among LAWs involved in cleaning tasks

    Staphylococcal Biofilm Exopolysaccharide Protects against Caenorhabditis elegans Immune Defenses

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    Staphylococcus epidermidis and Staphylococcus aureus are leading causes of hospital-acquired infections that have become increasingly difficult to treat due to the prevalence of antibiotic resistance in these organisms. The ability of staphylococci to produce biofilm is an important virulence mechanism that allows bacteria both to adhere to living and artificial surfaces and to resist host immune factors and antibiotics. Here, we show that the icaADBC locus, which synthesizes the biofilm-associated polysaccharide intercellular adhesin (PIA) in staphylococci, is required for the formation of a lethal S. epidermidis infection in the intestine of the model nematode Caenorhabditis elegans. Susceptibility to S. epidermidis infection is influenced by mutation of the C. elegans PMK-1 p38 mitogen-activated protein (MAP) kinase or DAF-2 insulin-signaling pathways. Loss of PIA production abrogates nematocidal activity and leads to reduced bacterial accumulation in the C. elegans intestine, while overexpression of the icaADBC locus in S. aureus augments virulence towards nematodes. PIA-producing S. epidermidis has a significant survival advantage over ica-deficient S. epidermidis within the intestinal tract of wild-type C. elegans, but not in immunocompromised nematodes harboring a loss-of-function mutation in the p38 MAP kinase pathway gene sek-1. Moreover, sek-1 and pmk-1 mutants are equally sensitive to wild-type and icaADBC-deficient S. epidermidis. These results suggest that biofilm exopolysaccharide enhances virulence by playing an immunoprotective role during colonization of the C. elegans intestine. These studies demonstrate that C. elegans can serve as a simple animal model for studying host–pathogen interactions involving staphylococcal biofilm exopolysaccharide and suggest that the protective activity of biofilm matrix represents an ancient conserved function for resisting predation

    The Code of Protest. Images of Peace in the West German Peace Movements, 1945-1990

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    The article examines posters produced by the peace movements in the Federal Republic of Germany during the ColdWar, with an analytical focus on the transformation of the iconography of peace in modernity. Was it possible to develop an independent, positive depiction of peace in the context of protests for peace and disarmament? Despite its name, the pictorial selfrepresentation of the campaign ‘Fight against Nuclear Death’ in the late 1950s did not draw on the theme of pending nuclear mass death. The large-scale protest movement in the 1980s against NATO’s 1979 ‘double-track’ decision contrasted female peacefulness with masculine aggression in an emotionally charged pictorial symbolism. At the same time this symbolism marked a break with the pacifist iconographic tradition that had focused on the victims of war. Instead, the movement presented itself with images of demonstrating crowds, as an anticipation of its peaceful ends. Drawing on the concept of asymmetrical communicative ‘codes’ that has been developed in sociological systems theory, the article argues that the iconography of peace in peace movement posters could not develop a genuinely positive vision of peace, since the code of protest can articulate the designation value ‘peace’ only in conjunction with the rejection value ‘war’

    A Methodology for the Classification and Characterisation of Industrial Demand-Side Integration Measures

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    In the context of the ongoing climate change and increasingly strict climate goals of the European Green Deal, industry faces a growing challenge to decrease its high demand for electrical energy and its greenhouse gas emissions. Demand-Side Integration measures have a great potential to reduce the greenhouse gas emissions of the industrial sector. However, there is still no definition and consistent characterising terms for Industrial Demand-Side Integration. The lack of clarity in concepts and definitions may impose hurdles in the transfer of results and methodologies from research activities and thus, in the implementation of measures in the industry. Furthermore, the economic value of implementing these measures is often unclear but of high relevance to industrial consumers. This paper proposes a comprehensive Industrial Demand-Side Integration definition and a methodology to classify and characterise its measures. The methodology is aimed at helping industrial consumers decide which measures can be implemented in their specific setting and how these measures can be monetised. The methodology is validated by applying it to eight relevant use cases in the ETA Research Factory
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