274 research outputs found

    BLM and RMI1 alleviate RPA inhibition of topoIIIα decatenase activity

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    RPA is a single-stranded DNA binding protein that physically associates with the BLM complex. RPA stimulates BLM helicase activity as well as the double Holliday junction dissolution activity of the BLM-topoisomerase IIIα complex. We investigated the effect of RPA on the ssDNA decatenase activity of topoisomerase IIIα. We found that RPA and other ssDNA binding proteins inhibit decatenation by topoisomerase IIIα. Complex formation between BLM, TopoIIIα, and RMI1 ablates inhibition of decatenation by ssDNA binding proteins. Together, these data indicate that inhibition by RPA does not involve species-specific interactions between RPA and BLM-TopoIIIα-RMI1, which contrasts with RPA modulation of double Holliday junction dissolution. We propose that topoisomerase IIIα and RPA compete to bind to single-stranded regions of catenanes. Interactions with BLM and RMI1 enhance toposiomerase IIIα activity, promoting decatenation in the presence of RPA

    Rmi1 stimulates decatenation of double Holliday junctions during dissolution by Sgs1-Top3

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    double Holliday junction (dHJ) is a central intermediate of homologous recombination that can be processed to yield crossover or non-crossover recombination products. To preserve genomic integrity, cells possess mechanisms to avoid crossing over. We show that Saccharomyces cerevisiae Sgs1 and Top3 proteins are sufficient to migrate and disentangle a dHJ to produce exclusively non-crossover recombination products, in a reaction termed "dissolution." We show that Rmi1 stimulates dHJ dissolution at low Sgs1-Top3 protein concentrations, although it has no effect on the initial rate of Holliday junction (HJ) migration. Rmi1 serves to stimulate DNA decatenation, removing the last linkages between the repaired and template DNA molecules. Dissolution of a dHJ is a highly efficient and concerted alternative to nucleolytic resolution that prevents crossing over of chromosomes during recombinational DNA repair in mitotic cells and thereby contributes to genomic integrity

    Institutional Strategies in Emerging Markets

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    We review and integrate a wide range of literature that has examined the strategies by which organizations navigate institutionally diverse settings and capture rents outside of the marketplace. We synthesize this body of research under the umbrella term institutional strategies, which we define as the comprehensive set of plans and actions directed at strategically leveraging and shaping the socio-political and cultural institutions within an organization’s external environment. Our review of institutional strategies is focused on emerging market contexts, settings that are characterized by weak capital market and regulatory infrastructures and fast-paced turbulent change. Under such challenging conditions, strategies aimed at shaping the institutional environment may be especially critical to an organization’s performance and long-term survival. Our review reveals that organizations engage in three specific and identifiable sets of institutional strategies, which we term: relational, infrastructure-building, and socio-cultural bridging. We conclude by highlighting fruitful avenues for cross-disciplinary dialogue in the hope of promoting future research on emerging markets and defining the next frontier of institutional theory in organizational analysis

    Ground-based detection of G star superflares with NGTS

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    We present high cadence detections of two superflares from a bright G8 star (V = 11.56) with the Next Generation Transit Survey (NGTS). We improve upon previous superflare detections by resolving the flare rise and peak, allowing us to fit a solar flare inspired model without the need for arbitrary break points between rise and decay. Our data also enables us to identify substructure in the flares. From changing starspot modulation in the NGTS data we detect a stellar rotation period of 59 hours, along with evidence for differential rotation. We combine this rotation period with the observed \textit{ROSAT} X-ray flux to determine that the star's X-ray activity is saturated. We calculate the flare bolometric energies as 5.40.7+0.8×10345.4^{+0.8}_{-0.7}\times10^{34} and 2.60.3+0.4×10342.6^{+0.4}_{-0.3}\times10^{34} erg and compare our detections with G star superflares detected in the \textit{Kepler} survey. We find our main flare to be one of the largest amplitude superflares detected from a bright G star. With energies more than 100 times greater than the Carrington event, our flare detections demonstrate the role that ground-based instruments such as NGTS can have in assessing the habitability of Earth-like exoplanets, particularly in the era of \textit{PLATO}

    Socioeconomic Status and Racial and Ethnic Differences in Functional Status Associated with Chronic Diseases

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    Objectives. This study examined the relationships between wealth and income and selected racial and ethnic differences in health. Methods. Cross-sectional data on a national sample of 9744 men and women aged 51 through 61 from the 1992 Health and Retirement Survey were analyzed to examine the association between socioeconomic status and racial and ethnic differences in functional status among those with hypertension, diabetes, a heart condition, and arthritis. Results. Compared with Whites, African Americans report higher rates of hypertension, diabetes, and arthritis, while Hispanics report higher rates of hypertension and diabetes and a lower rate of heart conditions. Accounting for differences in education, income, and wealth had little effect on these prevalence differences. In general, among those with chronic diseases, African Americans and Hispanics reported worse function than Whites. This disadvantage was eliminated in every case by controlling for socioeconomic status. Conclusions. While socioeconomic status, including wealth, accounts for much of the difference in functional status associated with these chronic diseases, it plays a relatively small role in explaining differences in the prevalence of chronic disease, possibly reflecting different causal pathways.

    The Crystal Structure and RNA-Binding of an Orthomyxovirus Nucleoprotein

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    Genome packaging for viruses with segmented genomes is often a complex problem. This is particularly true for influenza viruses and other orthomyxoviruses, whose genome consists of multiple negative-sense RNAs encapsidated as ribonucleoprotein (RNP) complexes. To better understand the structural features of orthomyxovirus RNPs that allow them to be packaged, we determined the crystal structure of the nucleoprotein (NP) of a fish orthomyxovirus, the infectious salmon anemia virus (ISAV) (genus Isavirus). As the major protein component of the RNPs, ISAV-NP possesses a bi-lobular structure similar to the influenza virus NP. Because both RNA-free and RNA-bound ISAV NP forms stable dimers in solution, we were able to measure the NP RNA binding affinity as well as the stoichiometry using recombinant proteins and synthetic oligos. Our RNA binding analysis revealed that each ISAV-NP binds ,12 nts of RNA, shorter than the 24ヨ28 nts originally estimated for the influenza A virus NP based on population average. The 12-nt stoichiometry was further confirmed by results from electron microscopy and dynamic light scattering. Considering that RNPs of ISAV and the influenza viruses have similar morphologies and dimensions, our findings suggest that NP-free RNA may exist on orthomyxovirus RNPs, and selective RNP packaging may be accomplished through direct RNA-RNA interactions
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