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  • 1
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 103 (1980), S. 489-502 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Previous studies (J. Biol. Chem, 253: 99-105, 1978) showed that thyrotropin-releasing hormone (TRH) acutely stimulated uridine uptake in pituitary cell (GH4C1) cultures. Studies on the role of protein synthesis in this response to TRH led to the finding that an inhibitor of ribosomal translation, cycloheximide, also stimulated uridine uptake acutely. Studies reported here attempt to determine the mechanism of cycloheximide action and whether cycloheximide and hormone stimulation of uridine uptake occurred by similar pathways. The experiments presented indicate that: (1) seven inhibitors of ribosomal translation stimulated uridine uptake; (2) in contrast, inhibition of protein synthesis at tRNA aminoacylation resulted in reduced rates of uridine uptake; (3) inhibition of tRNA aminoacylation blocked cycloheximide but not TRH stimulation of uptake; (4) cycloheximide stimulation of uptake was restricted to amino acid-depleted cultures; (5) amino acid supplementation stimulated uridine uptake with a time-course identical to that of cycloheximide; (6) cycloheximide and amino acid supplementation promoted reacylation of cellular tRNAs in amino acid-depleted cultures; and (7) cycloheximide stimulation of uridine uptake resulted from enhanced nucleoside phosphorylation rather than increased uridine transport. We conclude that cycloheximide and amino acid stimulation of uridine phosphorylation may be mediated through a common pathway involving the extent of amino-acylation of cellular tRNAs. Furthermore, cycloheximide and TRH stimulate uridine phosphorylation by pathways that are distinguishable. It is apparent that not all cellular effects of cycloheximde can be attributed solely to inhibition of the synthesis of proteins.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 109 (1981), S. 289-297 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: GH pituitary cells have been widely utilized for studies of hormone response mechanisms. Studies reported here were motivated by the desirability of isolating characterized GH clones defective in cyclic AMP synthesis or action. Spontaneously occurring GH1 cell variants resistant to the growthinhibitory effects of cyclic AMP analogs were isolated. Characterization of four variants showed that these were deficient in adenosine kinase and had acquired resistance to the cytotoxic effects of purine nucleoside derivatives formed in the culture medium. A second-stage selection was undertaken with mutagenized adenosine kinase-deficient cells. One 8 Br cAMP-resistant variant was found to have normal cyclic AMP-dependent protein kinase activity but exhibited altered adenylate cyclase activity. Activation of cyclase activity by fluoride, guanyl nucleotides, cholera toxin, and hormone (VIP) was subnormal in the variant. Mndependent cyclase activity was also subnormal, suggesting that the 8 Br cAMP-resistant variant may have a deficiency in the catalytic moiety of adenylate cyclase.Surprisingly, adenosine 3′ :5′ -monophosphate and 5′ -monophosphate derivatives were found to be equally potent in growth-inhibiting adenosine kinasedeficient cells. Cross-resistance to 8 Br AMP was observed in the 8 Br cAMP-resistant variant. We conclude that cyclic AMP derivatives inhibit growth of GH cells by an unanticipated mechanism that is, nonetheless, related to endogenous cyclic AMP synthesis.
    Additional Material: 9 Ill.
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  • 3
    Publication Date: 2017-03-21
    Description: Deep-water benthic communities in the ocean are almost wholly dependent on near-surface pelagic ecosystems for their supply of energy and material resources. Primary production in sunlit surface waters is channelled through complex food webs that extensively recycle organic material, but lose a fraction as particulate organic carbon (POC) that sinks into the ocean interior. This exported production is further rarefied by microbial breakdown in the abyssal ocean, but a residual ultimately drives diverse assemblages of seafloor heterotrophs. Advances have led to an understanding of the importance of size (body mass) in structuring these communities. Here we force a size-resolved benthic biomass model, BORIS, using seafloor POC flux from a coupled ocean-biogeochemistry model, NEMO-MEDUSA, to investigate global patterns in benthic biomass. BORIS resolves 16 size-classes of metazoans, successively doubling in mass from approximately 1 μ g to 28mg. Simulations find a wide range of seasonal responses to differing patterns of POC forcing, with both a decline in seasonal variability, and an increase in peak lag times with increasing body size. However, the dominant factor for modelled benthic communities is the integrated magnitude of POC reaching the seafloor rather than its seasonal pattern. Scenarios of POC forcing under climate change and ocean acidification are then applied to investigate how benthic communities may change under different future conditions. Against a backdrop of falling surface primary production (-6.1%), and driven by changes in pelagic remineralisation with depth, results show that while benthic communities in shallow seas generally show higher biomass in a warmed world (+3.2%), deep-sea communities experience a substantial decline (-32%) under a high greenhouse gas emissions scenario. Our results underscore the importance for benthic ecology of reducing uncertainty in the magnitude and seasonality of seafloor POC fluxes, as well as the importance of studying a broader range of seafloor environments for future model development. This article is protected by copyright. All rights reserved.
    Print ISSN: 1354-1013
    Electronic ISSN: 1365-2486
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Geography
    Published by Wiley-Blackwell
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  • 4
    Publication Date: 2012-05-08
    Description: Purpose: To evaluate intrinsic hepatic enhancement patterns on multiphase, gadolinium-enhanced, fat-suppressed, 3D T1-weighted, gradient echo magnetic resonance imaging (MRI) as a quantitative correlate for severity of pathological changes in chronic liver disease (CLD). Materials and Methods: This study was HIPAA-compliant and Institutional Review Board-approved. In all, 75 patients were studied by contrast-enhanced multiphase abdominal MRI. CLD patients had liver histology correlation derived from right lobe liver biopsies. Contrast-enhanced arterial- and delayed-phase 3D gradient recalled echo (GRE) liver MRI were scored using feature categorization templates to quantify enhancement patterns by three independent readers. Liver histopathology was staged/graded for fibrosis/inflammation using the Scheuer system. Statistical testing for MRI histology correlates used a Pearson's product moment correlation and a Wilcoxon–Mann–Whitney two-sample rank-sum test. Reader agreement was analyzed by a modified Fleiss' kappa test. Results: MRI histology correlation was high for delayed-phase MRI versus fibrosis stage (95% confidence interval [CI] 0.941 〈 r 〈 0.976, P = 5 × 10 −7 ), but lower for all other comparisons (delayed-phase vs. inflammation and arterial-phase vs. inflammation or fibrosis all showed a CI no greater than 0.64). Paired testing between delayed-phase MRI score and histology fibrosis staging incremental levels was significant (from P 〈 10 −2 to P 〈 10 −5 ). Conclusion: A standard gadolinium-enhanced liver MRI may provide a correlate measure of hepatic fibrosis over a spectrum of severity. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 5
    Publication Date: 2013-07-31
    Description: [1]  The transport of sand in saltation is driven by the persistently unsteady stresses exerted by turbulent winds. Based on coupled high-frequency observations of wind velocity and sand flux on a desert dune during intermittent saltation, we show here how observations of saltation by natural winds depend significantly on the time scale and method used for determining shear stress and sand flux. The correlation between sand flux and excess shear stress (stress above a threshold value) systematically improves for longer averaging time scale, T , and is better for stress determined by the law-of-the-wall versus the Reynolds stress method. Fitting parameters for the stress-flux relationship do not converge with increasing T , which may be explained by the non-stationary nature of wind velocity statistics. We show how it may be possible, based on the scale-dependent statistics of stress fluctuations, to re-scale saltation flux predictions for wind observations made at different timescales. However, our observations indicate hysteresis and time lags in thresholds for initiation and cessation of saltation, which complicate threshold-based approaches to predicting sediment transport at different time scales.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
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  • 6
    Publication Date: 2014-12-04
    Description: Aims Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients. Methods and results First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using 125 Iodine-human serum albumin. Second, we derived PVS as: [(calculated aPV – ideal PV)/ideal PV] × 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val-HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val-HeFT cohort, mean (+SD) PVS was –9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a ‘J-shaped’ fashion with the highest risk seen with a PVS 〉 –4%. Stratification into PVS quartiles confirmed that a PVS 〉 –4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44–1.88, χ 2  = 54, P  〈 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort. Conclusions Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS-driven CHF management needs further evaluation.
    Print ISSN: 1388-9842
    Electronic ISSN: 1879-0844
    Topics: Medicine
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