Detoxification of Pesticide Residues in Soil Using Phytoremediation

During the past few years, we have conducted a series of experiments to investigate the potential of using plants as tools for the remediation of pesticide-contaminated soil. We have demonstrated that a blend of prairie grasses increases dissipation rates of several pesticides including metolachlor, trifluralin, and pendimethalin. However, in other studies, mulberry trees were not shown to influence pesticide dissipation. Additional studies have demonstrated that metolachlor movement in the soil column may be reduced by the presence of prairie grasses, bioavailability of dinitroanaline herbicides may be reduced during phytoremediation, and soil and leachate from remediated soil may have less toxicity than expected. Current studies within our laboratory are being conducted to determine the role of prairie grass blends in the phytoremediation procedure as compared to individual species and the role of plant uptake of pesticides in the phytoremediation process

Persistence, Mobility, and Bioavailability of Pendimethalin and Trifluralin in Soil

Pendimethalin and trifluralin are current-use pesticides that have been previously reported as persistent, bioaccumulative, and toxic. In the studies presented here, dissipation of aged and fresh residues of pendimethalin and trifluralin were evaluated in soil, as well as the bioavailability of residues to earthworms and the movement of pendimethalin in a soil column. In a separate study, pond water receiving runoff from a golf course was measured for the presence of pendimethalin. Dissipation measurements of pendimethalin and trifluralin in soil indicated very slow dissipation with 40-60% of the compounds extractable at 1026 days after the first measurement. In a second study, dissipation of pendimethalin was more rapid, however more than 30% was present after 310 days of soil treatment. Biovailability, as measured by earthworm biological accumulation factors, was reduced over time. Mobility of pendimethalin was very limited. Almost no downward movement was measured in the column study, and no detectable levels were found in runoff from turf grass

More than skin deep: Functional genomic basis for resistance to Amphibian Chytridiomycosis

The amphibian-killing chytrid fungus Batrachochytriumdendrobatidis (Bd) is one of themost generalist pathogens known, capable of infecting hundreds of species globally and causing widespread population declines and extinctions. However, some host species are seemingly unaffected by Bd, tolerating or clearing infections without clinical signs of disease. Variation in host immune responses is commonly evoked for these resistant or tolerant species, yet to date,we have nodirect comparisonof amphibian species responses to infection at the level of gene expression. In this study,we challenged four CentralAmerican frog species that vary in Bd susceptibility, with a sympatric virulent strain of the pathogen. We compared skin and spleen orthologous gene expression using differential expression tests and coexpression gene network analyses.Wefound that resistant species have reduced skin inflammatory responses andincreased expressionofgenes involved inskin integrity. Incontrast, onlyhighly susceptible species exhibited suppressionof splenic T-cell genes. We conclude that resistance to chytridiomycosis may be related to a species’ ability to escape the immunosuppressive activity of the fungus. Moreover, our results indicate that within-species differences in splenic proteolytic enzyme gene expression may contribute to intraspecific variation in survival. This first comparison of amphibian functional immunogenomic architecture in response to Bd provides insights into key genetic mechanisms underlying variation in disease outcomes among amphibian species

Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study.

OBJECTIVES: To examine whether the overall results of the CASTLE study pertain to both genders, we analysed the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir in 277 female and 606 male patients in the open-label, multinational trial over 96 weeks. The trial is registered with ClinicalTrials.gov, number NCT00272779. METHODS: Treatment-naive patients aged ≥ 18 years with HIV-1 RNA ≥ 5000 copies/mL were randomized to receive either atazanavir/ritonavir 300/100 mg once daily or lopinavir/ritonavir 400/100 mg twice daily, with fixed-dose tenofovir/emtricitabine 300/200 mg once daily. RESULTS: At week 96, confirmed virological response rates (HIV RNA \u3c50 copies\u3e/mL; intent-to-treat analysis) were higher in women and men receiving atazanavir/ritonavir than those receiving lopinavir/ritonavir and lower in women than men in both treatment arms (67% of women and 77% of men on atazanavir/ritonavir and 63% of women and 71% of men on lopinavir/ritonavir). These differences were not observed in the on-treatment analysis. Mean change in CD4 cell count from baseline to week 96 was 265 cells/mm(3) for women and 269 cells/mm(3) for men on atazanavir/ritonavir and 298 cells/mm(3) for women and 286 cells/mm(3) for men on lopinavir/ritonavir. Discontinuation rates were higher in women than men in each treatment arm (22% of women and 15% of men on atazanavir/ritonavir and 29% of women and 18% of men on lopinavir/ritonavir). In women and men, grade 2-4 nausea and diarrhoea were more frequent in the lopinavir/ritonavir group; jaundice and hyperbilirubinaemia occurred more frequently in the atazanavir/ritonavir group. CONCLUSIONS: Once-daily atazanavir/ritonavir is an effective and well-tolerated therapeutic option for women and men with HIV-1 infection. The sex-based differences in response may be due to higher discontinuation rates in women

Patient judgments about hypertension control: The role of variability, trends, and outliers in visualized blood pressure data

Background: Uncontrolled hypertension is a significant health problem in the United States, even though multiple drugs exist to effectively treat this chronic disease. Objective: As part of a larger project developing data visualizations to support shared decision making about hypertension treatment, we conducted a series of studies to understand how perceptions of hypertension control were impacted by data variations inherent in the visualization of blood pressure (BP) data. Methods: In 3 Web studies, participants (internet sample of patients with hypertension) reviewed a series of vignettes depicting patients with hypertension; each vignette included a graph of a patient's BP. We examined how data visualizations that varied by BP mean and SD (Study 1), the pattern of change over time (Study 2), and the presence of extreme values (Study 3) affected patients' judgments about hypertension control and the need for a medication change. Results: Participants' judgments about hypertension control were significantly influenced by BP mean and SD (Study 1), data trends (whether BP was increasing or decreasing over time--Study 2), and extreme values (ie, outliers--Study 3). Conclusions: Patients' judgment about hypertension control is influenced both by factors that are important predictors of hypertension related-health outcomes (eg, BP mean) and factors that are not (eg, variability and outliers). This study highlights the importance of developing data visualizations that direct attention toward clinically meaningful information

A Gain-of-Function Germline Mutation in Drosophila ras1 Affects Apoptosis and Cell Fate during Development

The RAS/MAPK signal transduction pathway is an intracellular signaling cascade that transmits environmental signals from activated receptor tyrosine kinases (RTKs) on the cell surface and other endomembranes to transcription factors in the nucleus, thereby linking extracellular stimuli to changes in gene expression. Largely as a consequence of its role in oncogenesis, RAS signaling has been the subject of intense research efforts for many years. More recently, it has been shown that milder perturbations in Ras signaling during embryogenesis also contribute to the etiology of a group of human diseases. Here we report the identification and characterization of the first gain-of-function germline mutation in Drosophila ras1 (ras85D), the Drosophila homolog of human K-ras, N-ras and H-ras. A single amino acid substitution (R68Q) in the highly conserved switch II region of Ras causes a defective protein with reduced intrinsic GTPase activity, but with normal sensitivity to GAP stimulation. The ras1R68Q mutant is homozygous viable but causes various developmental defects associated with elevated Ras signaling, including cell fate changes and ectopic survival of cells in the nervous system. These biochemical and functional properties are reminiscent of germline Ras mutants found in patients afflicted with Noonan, Costello or cardio-facio-cutaneous syndromes. Finally, we used ras1R68Q to identify novel genes that interact with Ras and suppress cell death

Cutaneous Bacteria of the Redback Salamander Prevent Morbidity Associated with a Lethal Disease

Chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), is an infectious disease that causes population declines of many amphibians. Cutaneous bacteria isolated from redback salamanders, Plethodon cinereus, and mountain yellow-legged frogs, Rana muscosa, inhibit the growth of Bd in vitro. In this study, the bacterial community present on the skin of P. cinereus individuals was investigated to determine if it provides protection to salamanders from the lethal and sub-lethal effects of chytridiomycosis. When the cutaneous bacterial community was reduced prior to Bd exposure, salamanders experienced a significantly greater decrease in body mass, which is a symptom of the disease, when compared to infected individuals with a normal bacterial community. In addition, a greater proportion of infected individuals with a reduced bacterial community experienced limb-lifting, a behavior seen only in infected individuals. Overall, these results demonstrate that the cutaneous bacterial community of P. cinereus provides protection to the salamander from Bd and that alteration of this community can change disease resistance. Therefore, symbiotic microbes associated with this species appear to be an important component of its innate skin defenses

Systems Biology of the Clock in Neurospora crassa

A model-driven discovery process, Computing Life, is used to identify an ensemble of genetic networks that describe the biological clock. A clock mechanism involving the genes white-collar-1 and white-collar-2 (wc-1 and wc-2) that encode a transcriptional activator (as well as a blue-light receptor) and an oscillator frequency (frq) that encodes a cyclin that deactivates the activator is used to guide this discovery process through three cycles of microarray experiments. Central to this discovery process is a new methodology for the rational design of a Maximally Informative Next Experiment (MINE), based on the genetic network ensemble. In each experimentation cycle, the MINE approach is used to select the most informative new experiment in order to mine for clock-controlled genes, the outputs of the clock. As much as 25% of the N. crassa transcriptome appears to be under clock-control. Clock outputs include genes with products in DNA metabolism, ribosome biogenesis in RNA metabolism, cell cycle, protein metabolism, transport, carbon metabolism, isoprenoid (including carotenoid) biosynthesis, development, and varied signaling processes. Genes under the transcription factor complex WCC ( = WC-1/WC-2) control were resolved into four classes, circadian only (612 genes), light-responsive only (396), both circadian and light-responsive (328), and neither circadian nor light-responsive (987). In each of three cycles of microarray experiments data support that wc-1 and wc-2 are auto-regulated by WCC. Among 11,000 N. crassa genes a total of 295 genes, including a large fraction of phosphatases/kinases, appear to be under the immediate control of the FRQ oscillator as validated by 4 independent microarray experiments. Ribosomal RNA processing and assembly rather than its transcription appears to be under clock control, suggesting a new mechanism for the post-transcriptional control of clock-controlled genes