570 research outputs found

    Field-scale remediation of atrazine-contaminated soil using recombinant Escherichia coli expressing atrazine chlorohydrolase

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    We performed the first field-scale atrazine remediation study in the United States using chemically killed, recombinant organisms. This field study compared biostimulation methods for enhancing atrazine degradation with a novel bioaugmentation protocol using a killed and stabilized whole-cell suspension of recombinant Escherichia coli engineered to overproduce atrazine chlorohyrolase, AtzA. AtzA dechlorinates atrazine, producing non-toxic and non-phytotoxic hydroxyatrazine. Soil contaminated by an accidental spill of atrazine (up to 29 000 p.p.m.) supported significant populations of indigenous microorganisms capable of atrazine catabolism. Laboratory experiments indicated that supplementing soil with carbon inhibited atrazine biodegradation, but inorganic phosphate stimulated atrazine biodegradation. A subsequent field-scale study consisting of nine (0.75m3) treatment plots was designed to test four treatment protocols in triplicate. Control plots contained moistened soil; biostimulation plots received 300 p.p.m. phosphate; bioaugmentation plots received 0.5% (w/w) killed, recombinant E. coli cells encapsulating AtzA; and combination plots received phosphate plus the enzyme-containing cells. After 8 weeks, atrazine levels declined 52% in plots containing killed recombinant E. coli cells, and 77% in combination plots. In contrast, atrazine levels in control and biostimulation plots did not decline significantly. These data indicate that genetically engineered bacteria overexpressing catabolic genes significantly increased degradation in this soil heavily contaminated with atrazine

    Integrated stratigraphy of Pliensbachian and Toarcian strata from the northern Neuquén Basin, Argentina

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    The Toarcian Oceanic Anoxic Event (T-OAE, ~183 Ma) was marked by globally recognized environmental perturbations, most notably disturbances to the global carbon cycle and climate. To date, geochemical records providing information about the T-OAE have been largely generated from the warm temperate climate zone of the NW European realm. Coeval geochemical records from the Southern Hemisphere, providing a more global perspective on palaeoenvironmental changes associated with the T-OAE, are comparatively scarce. In this study, we present a biostratigraphically calibrated litho- and chemostratigraphic recordof Lower Jurassic strata from the northern Neuquén Basin, Argentina, covering the Upper Pliensbachian and Toarcian upper tenuicostatum to lower Dumortieria Andean ammonite zones, equivalent to the uppermost tenuicostatum to pseudoradiosa European standard zones. The integrated stratigraphic data re-define the stratigraphic position of the Andean tenuicostatum–D. hoelderi ammonite Zone boundary and support near-synchroneity of this horizon with the tenuicostatum–serpentinum zonal boundary in NW Europe. The stratigraphic interval recording the negative carbon-isotope excursion associated with the T-OAE appears massively expanded and organic lean in contrast to the coeval organic-rich deposits in other parts of the Neuquén Basin and in European sections. At Las Overas, persistent sedimentary organic-matter enrichment was limited to brief intervals of black-shale deposition, possibly coinciding with reduced sedimentary organic matter dilution. Depositional rates and inorganic redox proxies suggest that the development of oxygen-depleted conditions may have been disrupted by the interplay between basin subsidence, sedimentation rate, relative sea-level change, depositional setting and deep-water currents.Fil: Storm, Marisa S.. Netherland Institute For Sea Research; Países BajosFil: Hesselbo, Stephen P.. University of Oxford; Reino UnidoFil: Jenkyns, Hugh C.. University of Oxford; Reino UnidoFil: Ruhl, Micha. University of Oxford; Reino UnidoFil: Al Suwaidi, Aisha. Khalifa University of Science and Technology; Emiratos Arabes UnidosFil: Percival, Lawrence M.. Vrije Universiteit Amsterdam; Países BajosFil: Mather, Tamsin A.. University of Oxford; Reino UnidoFil: Damborenea, Susana Ester. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Departamento de Paleontología Invertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Manceñido, Miguel Oscar. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Departamento de Paleontología Invertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Riccardi, Alberto Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Departamento de Paleontología Invertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

    Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study.

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    Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD

    Progression of MRI markers in cerebral small vessel disease: sample size considerations for clinical trials.

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    Detecting treatment efficacy using cognitive change in trials of cerebral small vessel disease (SVD) has been challenging, making the use of surrogate markers such as magnetic resonance imaging (MRI) attractive. We determined the sensitivity of MRI to change in SVD and used this information to calculate sample size estimates for a clinical trial. Data from the prospective SCANS (St George's Cognition and Neuroimaging in Stroke) study of patients with symptomatic lacunar stroke and confluent leukoaraiosis was used (n=121). Ninety-nine subjects returned at one or more time points. Multimodal MRI and neuropsychologic testing was performed annually over 3 years. We evaluated the change in brain volume, T2 white matter hyperintensity (WMH) volume, lacunes, and white matter damage on diffusion tensor imaging (DTI). Over 3 years, change was detectable in all MRI markers but not in cognitive measures. WMH volume and DTI parameters were most sensitive to change and therefore had the smallest sample size estimates. MRI markers, particularly WMH volume and DTI parameters, are more sensitive to SVD progression over short time periods than cognition. These markers could significantly reduce the size of trials to screen treatments for efficacy in SVD, although further validation from longitudinal and intervention studies is required.Journal of Cerebral Blood Flow & Metabolism advance online publication, 3 June 2015; doi:10.1038/jcbfm.2015.113

    Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability

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    The simian immunodeficiency virus (SIV) challenge model of lentiviral infection is often used as a model to human immunodeficiency virus type 1 (HIV-1) for studying vaccine mediated and immune correlates of protection. However, knowledge of the structure of the SIV envelope (Env) glycoprotein is limited, as is knowledge of binding specificity, function and potential efficacy of SIV antibody responses. In this study we describe the use of a competitive probe binding sort strategy as well as scaffolded probes for targeted isolation of SIV Env-specific monoclonal antibodies (mAbs). We isolated nearly 70 SIV-specific mAbs directed against major sites of SIV Env vulnerability analogous to broadly neutralizing antibody (bnAb) targets of HIV-1, namely, the CD4 binding site (CD4bs), CD4-induced (CD4i)-site, peptide epitopes in variable loops 1, 2 and 3 (V1, V2, V3) and potentially glycan targets of SIV Env. The range of SIV mAbs isolated includes those exhibiting varying degrees of neutralization breadth and potency as well as others that demonstrated binding but not neutralization. Several SIV mAbs displayed broad and potent neutralization of a diverse panel of 20 SIV viral isolates with some also neutralizing HIV-27312A. This extensive panel of SIV mAbs will facilitate more effective use of the SIV non-human primate (NHP) model for understanding the variables in development of a HIV vaccine or immunotherapy
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