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Hoang M.L.,Howard Hughes Medical Institute | Hoang M.L.,Johns Hopkins University | Tan F.J.,Howard Hughes Medical Institute | Tan F.J.,University of California at Berkeley | And 8 more authors.
PLoS Genetics | Year: 2010

Genome rearrangements often result from non-allelic homologous recombination (NAHR) between repetitive DNA elements dispersed throughout the genome. Here we systematically analyze NAHR between Ty retrotransposons using a genome-wide approach that exploits unique features of Saccharomyces cerevisiae purebred and Saccharomyces cerevisiae/ Saccharomyces bayanus hybrid diploids. We find that DNA double-strand breaks (DSBs) induce NAHR-dependent rearrangements using Ty elements located 12 to 48 kilobases distal to the break site. This break-distal recombination (BDR) occurs frequently, even when allelic recombination can repair the break using the homolog. Robust BDR-dependent NAHR demonstrates that sequences very distal to DSBs can effectively compete with proximal sequences for repair of the break. In addition, our analysis of NAHR partner choice between Ty repeats shows that intrachromosomal Ty partners are preferred despite the abundance of potential interchromosomal Ty partners that share higher sequence identity. This competitive advantage of intrachromosomal Tys results from the relative efficiencies of different NAHR repair pathways. Finally, NAHR generates deleterious rearrangements more frequently when DSBs occur outside rather than within a Ty repeat. These findings yield insights into mechanisms of repeat-mediated genome rearrangements associated with evolution and cancer. © 2010 Hoang et al.

Parrinello C.M.,Welch Center for Prevention | Rastegar I.,Welch Center for Prevention | Rastegar I.,Baltimore Polytechnic Institute | Godino J.G.,Welch Center for Prevention | And 5 more authors.
Diabetes Care | Year: 2015

OBJECTIVE: Controversy surrounds appropriate risk factor targets in older adults with diabetes. We evaluated the proportion of older adults with diabetes meeting different targets, focusing on possible differences by race, and assessed whether demographic and clinical characteristics explained disparities. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 5,018 participants aged 67-90 years (1,574 with and 3,444 without diagnosed diabetes) who attended visit 5 of the Atherosclerosis Risk in Communities (ARIC) study (2011-2013). Risk factor targets were defined using both stringent (and less stringent) goals: hemoglobin A1c (HbA1c) <7%, <53 mmol/mol (<8%, <64 mmol/mol); LDL cholesterol (LDL-c) <100 mg/dL (<130 mg/dL); and blood pressure (BP) <140/90 mmHg (<150/90 mmHg). We used Poisson regression to obtain prevalence ratios (PRs). RESULTS: Most older adults with diabetes met stringent (and less stringent) targets: 72% (90%) for HbA1c, 63% (86%) for LDL-c, and 73% (87%) for BP; but only 35% (68%) met all three. A higher proportion of whites than blacks met targets, however defined. Among people treated for risk factors, racial disparities in prevalence of meeting stringent targets persisted even after adjustment: PRs (whites vs. blacks) were 1.03 (95% CI 0.91, 1.17) for HbA1c, 1.21 (1.09, 1.35) for LDL-c, 1.10 (1.00, 1.21) for BP, and 1.28 (0.99, 1.66) for all three. Results were similar but slightly attenuated using less stringent goals. Black women were less likely than white women to meet targets for BP and all three risk factors; this disparity was not observed in men. CONCLUSIONS: Black-white disparities in risk factor control in older adults with diabetes were not fully explained by demographic or clinical characteristics and were greater in women than men. Further study of determinants of these disparities is important. © 2015 by the American Diabetes Association.

Higgins C.P.,Colorado School of Mines | Paesani Z.J.,Baltimore Polytechnic Institute | Halden R.U.,Arizona State University | Hundal L.S.,Metropolitan Water Reclamation District of Greater Chicago
Environmental Toxicology and Chemistry | Year: 2011

The presence of the antimicrobial chemicals triclocarban (TCC) and triclosan (TCS) in municipal biosolids has raised concerns about the potential impacts of these chemicals on soil ecosystems following land application of municipal biosolids. The relative persistence of TCC and TCS in agricultural fields receiving yearly applications of biosolids at six different loading rates over a three-year period was investigated. Soil and biosolids samples were collected, extracted, and analyzed for TCC and TCS using liquid chromatography-tandem mass spectrometry. In addition, the potential for bioaccumulation of TCC and TCS from the biosolids-amended soils was assessed over 28 d in the earthworm Eisenia foetida. Standard 28-d bioaccumulation tests were conducted for three biosolids loading rates from two sites, representing agronomic and twice the agronomic rates of biosolids application plots as well as control plots receiving no applications of biosolids. Additional bioaccumulation kinetic data were collected for the soils receiving the high biosolids loadings to ensure attainment of quasi steady-state conditions. The results indicate that TCC is relatively more persistent in biosolids-amended soil than TCS. In addition, TCC bioaccumulated in E. foetida, reaching body burdens of 25±4 and 133±17ng/gww in worms exposed for 28 d to the two soils amended with biosolids at agronomic rates. The 28-d organic carbon and lipid-normalized biota soil accumulation factors (BSAFs) were calculated for TCC and ranged from 0.22±0.12 to 0.71±0.13. These findings suggest that TCC bioaccumulation is somewhat consistent with the traditional hydrophobic organic contaminant (HOC) partitioning paradigm. However, these data also suggest substantially reduced bioavailability of TCC in biosolids-amended soils compared with HOC partitioning theory. Environ. Toxicol. Chem. 2011; 30:556-563. © 2011 SETAC Copyright © 2010 SETAC.

Rohrbaugh M.,Emory University | Kim J.,Emory University | Kithuka B.,Emory University | Mott B.,Emory University | And 22 more authors.
PLoS ONE | Year: 2013

Background: Strains from a collection of Drosophila GFP protein trap lines express GFP in the normal tissues where the endogenous protein is present. This collection can be used to screen for proteins distributed in the nucleus in a non-uniform pattern. Methodology/Principal Findings: We analyzed four lines that show peripheral or punctate nuclear staining. One of these lines affects an uncharacterized gene named CG11138. The CG11138 protein shows a punctate distribution in the nuclear periphery similar to that of Drosophila insulator proteins but does not co-localize with known insulators. Interestingly, mutations in Lamin proteins result in alterations in CG11138 localization, suggesting that this protein may be a novel component of the nuclear lamina. A second line affects the Decondensation factor 31 (Df31) gene, which encodes a protein with a unique nuclear distribution that appears to segment the nucleus into four different compartments. The X-chromosome of males is confined to one of these compartments. We also find that Drosophila Nucleoplasmin (dNlp) is present in regions of active transcription. Heat shock leads to loss of dNlp from previously transcribed regions of polytene chromosome without redistribution to the heat shock genes. Analysis of Stonewall (Stwl), a protein previously found to be necessary for the maintenance of germline stem cells, shows that Stwl is present in a punctate pattern in the nucleus that partially overlaps with that of known insulator proteins. Finally we show that Stwl, dNlp, and Df31 form part of a highly interactive network. The properties of other components of this network may help understand the role of these proteins in nuclear biology. Conclusions/Significance: These results establish screening of GFP protein trap alleles as a strategy to identify factors with novel cellular functions. Information gained from the analysis of CG11138 Stwl, dNlp, and Df31 sets the stage for future studies of these proteins. © 2013 Rohrbaugh et al.

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