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Search Results: 1 - 10 of 124613 matches for " Todd T. Brown "
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Causes of variation in soil carbon predictions from CMIP5 Earth system models and comparison with observations
K. E. O. Todd-Brown,J. T. Randerson,W. M. Post,F. M. Hoffman
Biogeosciences Discussions , 2012, DOI: 10.5194/bgd-9-14437-2012
Abstract: Stocks of soil organic carbon represent a large component of the carbon cycle that may participate in climate change feedbacks, particularly on decadal and century scales. For Earth system models (ESMs), the ability to accurately represent the global distribution of existing soil carbon stocks is a prerequisite for predicting future carbon-climate feedbacks. We compared soil carbon predictions from 16 ESMs to empirical data from the Harmonized World Soil Database (HWSD) and Northern Circumpolar Soil Carbon Database (NCSCD). Model estimates of global soil carbon stocks ranged from 510 to 3050 Pg C, compared to an estimate of 890–1660 Pg C from the HWSD. Model predictions for the high latitudes fell between 60 and 800 Pg C, compared to 380–620 Pg C from the NCSCD and 290 Pg C from the HWSD. This 5.3-fold variation in global soil carbon across models compared to a 3.4-fold variation in net primary productivity (NPP) and a 3.8-fold variation in global soil carbon turnover times. The spatial distribution of soil carbon predicted by the ESMs was not well correlated with the HWSD (Pearson's correlations < 0.4, RMSE 9.4 to 22.8 kg C m 2), although model-data agreement generally improved at the biome scale. There was poor agreement between the HWSD and NCSCD datasets in northern latitudes (Pearson's correlation = 0.33), indicating uncertainty in empirical estimates of soil carbon. We found that a reduced complexity model dependent on NPP and soil temperature explained most of the spatial variation in soil carbon predicted by most ESMs (R2 values between 0.73 and 0.93). This result suggests that differences in soil carbon predictions between ESMs are driven primarily by differences in predicted NPP and the parameterization of soil carbon responses to NPP and temperature not by structural differences between the models. Future work should focus on accurately representing these driving variables and modifying model structure to include additional processes.
Analysis of Proteolytic Processes and Enzymatic Activities in the Generation of Huntingtin N-Terminal Fragments in an HEK293 Cell Model
Andrew T. N. Tebbenkamp, Keith W. Crosby, Zoe B. Siemienski, Hilda H. Brown, Todd E. Golde, David R. Borchelt
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050750
Abstract: Background N-terminal fragments of mutant huntingtin (htt) that terminate between residues 90–115, termed cleavage product A or 1 (cp-A/1), form intracellular and intranuclear inclusion bodies in the brains of patients with Huntington's disease (HD). These fragments appear to be proteolytic products of the full-length protein. Here, we use an HEK293 cell culture model to investigate huntingtin proteolytic processing; previous studies of these cells have demonstrated cleavage of htt to cp-A/1 like htt fragments. Results Recombinant N-terminal htt fragments, terminating at residue 171 (also referred to as cp-B/2 like), were efficiently cleaved to produce cp-A/1 whereas fragments representing endogenous caspase, calpain, and metalloproteinase cleavage products, terminating between residues 400–600, were inefficiently cleaved. Using cysteine-labeling techniques and antibody binding mapping, we localized the C-terminus of the cp-A/1 fragments produced by HEK293 cells to sequences minimally limited by cysteine 105 and an antibody epitope composed of residues 115–124. A combination of genetic and pharmacologic approaches to inhibit potential proteases, including γ-secretase and calpain, proved ineffective in preventing production of cp-A/1. Conclusions Our findings indicate that HEK293 cells express a protease that is capable of efficiently cleaving cp-B/2 like fragments of htt with normal or expanded glutamine repeats. For reasons that remain unclear, this protease cleaves longer htt fragments, with normal or expanded glutamine expansions, much less efficiently. The protease in HEK293 cells that is capable of generating a cp-A/1 like htt fragment may be a novel protease with a high preference for a cp-B/2-like htt fragment as substrate.
Fat distribution and longitudinal anthropometric changes in HIV-infected men with and without clinical evidence of lipodystrophy and HIV-uninfected controls: A substudy of the Multicenter AIDS Cohort Study
Todd T Brown, Xiaoqiang Xu, Majnu John, Jaya Singh, Lawrence A Kingsley, Frank J Palella, Mallory D Witt, Joseph B Margolick, Adrian S Dobs
AIDS Research and Therapy , 2009, DOI: 10.1186/1742-6405-6-8
Abstract: Between 1999 and 2002, 33 men with clinical evidence of lipodystrophy (LIPO+), 23 HIV-infected men without clinical evidence of lipodytrophy (LIPO-), and 33 HIV-uninfected men were recruited from the four sites of the Multicenter AIDS Cohort Study (MACS). Participants underwent dual-energy x-ray absorptiometry, quantitative computerized tomography of the abdomen and thigh, and circumference measurements of the waist, hip and thigh. Circumference measurements at each semi-annual MACS visit between recruitment and 2008 were used to compare average annual anthropometric changes in the 3 groups.Body mass index (BMI) was lower in LIPO+ men than in the LIPO- men and the HIV- uninfected controls (BMI: 23.6 ± 0.4 vs 26.8 ± 1.5 vs 28.7 ± 0.9 kg/m2, respectively, p < 0.001). The average amount of visceral adipose tissue (VAT) was similar in all three groups (p = 0.26), but after adjustment for BMI, VAT was higher in the LIPO+ group (169 ± 10 cm2) compared to the LIPO- men (129 ± 12 cm2, p = 0.03) and the HIV-uninfected group (133 ± 11 cm2, p = 0.07). Subcutaneous adipose tissue (thigh, abdomen) and total extremity fat were less in the HIV-infected men (LIPO+ and LIPO-) than in the HIV-uninfected men. Over an average of 6 years of follow-up, waist circumference increased at a faster rate in LIPO+ group, compared to the LIPO- men (0.51 cm/year vs 0.08 cm/year, p = 0.02) and HIV-uninfected control men (0.21 cm/year, p = 0.06). The annual changes in hip and thigh circumferences were similar in all three groupsSubcutaneous lipoatrophy was observed in HIV-infected patients, even those without clinical evidence of lipodystrophy, compared to age-matched HIV-uninfected men. Despite markedly lower BMI, HIV-infected men with lipodystrophy had a similar amount of VAT as HIV-uninfected men and tended to have more rapid increases in waist circumference over 6 years of follow-up. These longitudinal increases in waist circumference may contribute to the development of cardiovascular risk in
Pharmacokinetic and metabolic effects of American ginseng (Panax quinquefolius) in healthy volunteers receiving the HIV protease inhibitor indinavir
Adriana SA Andrade, Craig Hendrix, Teresa L Parsons, Benjamin Caballero, Chun-Su Yuan, Charles W Flexner, Adrian S Dobs, Todd T Brown
BMC Complementary and Alternative Medicine , 2008, DOI: 10.1186/1472-6882-8-50
Abstract: After baseline assessment of insulin sensitivity using the insulin clamp technique, healthy volunteers received IDV 800 mg q8 h for 3 days and then IDV and AG 1g q8h for 14 days. IDV pharmacokinetics and insulin sensitivity were assessed before and after AG co-administration.There was no difference in the area-under the plasma-concentration-time curve after the co-administration of AG, compared to IDV alone (n = 13). Although insulin-stimulated glucose disposal per unit of insulin (M/I) decreased by an average of 14.8 ± 5.9% after 3 days of IDV (from 0.113 ± 0.012 to 0.096 ± 0.014 mg/kgFFM/min per μU/ml of insulin, p = 0.03, n = 11), M/I remained unchanged after co-administration of IDV and AG.IDV decreases insulin sensitivity, which is unaltered by AG co-administration. AG does not significantly affect IDV pharmacokinetics.Dietary supplements, herbs, and vitamins are used widely among HIV-infected patients [1]. However, the safety or efficacy of many of these therapies has not been formally evaluated.These agents are often used among HIV-infected patients to prevent or treat the adverse effects of antiretroviral therapy [2]. Among these adverse effects are disorders of glucose metabolism, including insulin resistance[3], glucose intolerance [4], and diabetes mellitus[3], which were described soon after the introduction of highly active antiretroviral therapy (HAART)[5]. Although the etiology of these problems is multifactorial [6], exposure to protease inhibitors (PIs) likely contributes directly. Indinavir (IDV), for example, can worsen insulin sensitivity even after a single dose in healthy volunteers[7].Ginseng is one of the most commonly used herbs in the United States [8] and has long been used for the treatment of hyperglycemia in Traditional Chinese Medicine [9]. Experimental evidence for its efficacy comes from several studies in both animals and humans [10]. In two small clinical trials, Panax ginseng [11] and AG [12] given daily over 8 weeks significantly
Microarray analysis of the in vivo sequence preferences of a minor groove binding drug
Todd T Eckdahl, Adam D Brown, Steven N Hart, Kelly J Malloy, Martha Shott, Gloria Yiu, Laura Hoopes, Laurie J Heyer
BMC Genomics , 2008, DOI: 10.1186/1471-2164-9-32
Abstract: Here we describe the use of microarray analysis to discover yeast genes that are affected by treatment with the MGBD berenil, thereby allowing the investigation of its sequence requirements for binding in vivo. A novel approach to sequence analysis allowed us to address hypotheses about genes that were directly or indirectly affected by drug binding. The results show that the sequence features of A/T richness and heteropolymeric character discovered by in vitro berenil binding studies are found upstream of genes hypothesized to be directly affected by berenil but not upstream of those hypothesized to be indirectly affected or those shown to be unaffected.The data support the conclusion that effects of berenil on gene expression in yeast cells can be explained by sequence patterns discovered by in vitro binding experiments. The results shed light on the sequence and structural rules by which berenil binds to DNA and affects the transcriptional regulation of genes and contribute generally to the development of MGBDs as tools for basic and applied research.Improved understanding of the sequence rules by which small molecules bind to DNA and alter patterns of gene expression advances both basic and applied research. In both of these contexts, molecules that bind noncovalently in the DNA minor groove with sequence-selective recognition have drawn considerable attention [1]. Minor groove binding drugs (MGBDs) have served as useful models for protein components of the transcriptional machinery since they can be more experimentally tractable than their macromolecular counterparts. For example, the understanding of the mechanism of action of TATA box binding protein, a general transcription factor required for proper initiation of transcription by RNA polymerase II, has been furthered using the MGBDs distamycin A, Hoechst 33258, and netropsin [2]. The observation that the MGBD berenil affects mitochondrial function and aerobic respiration in yeast suggests that it alters gen
Causes of variation in soil carbon simulations from CMIP5 Earth system models and comparison with observations
K. E. O. Todd-Brown, J. T. Randerson, W. M. Post, F. M. Hoffman, C. Tarnocai, E. A. G. Schuur,S. D. Allison
Biogeosciences (BG) & Discussions (BGD) , 2013,
Abstract: Stocks of soil organic carbon represent a large component of the carbon cycle that may participate in climate change feedbacks, particularly on decadal and centennial timescales. For Earth system models (ESMs), the ability to accurately represent the global distribution of existing soil carbon stocks is a prerequisite for accurately predicting future carbon–climate feedbacks. We compared soil carbon simulations from 11 model centers to empirical data from the Harmonized World Soil Database (HWSD) and the Northern Circumpolar Soil Carbon Database (NCSCD). Model estimates of global soil carbon stocks ranged from 510 to 3040 Pg C, compared to an estimate of 1260 Pg C (with a 95% confidence interval of 890–1660 Pg C) from the HWSD. Model simulations for the high northern latitudes fell between 60 and 820 Pg C, compared to 500 Pg C (with a 95% confidence interval of 380–620 Pg C) for the NCSCD and 290 Pg C for the HWSD. Global soil carbon varied 5.9 fold across models in response to a 2.6-fold variation in global net primary productivity (NPP) and a 3.6-fold variation in global soil carbon turnover times. Model–data agreement was moderate at the biome level (R2 values ranged from 0.38 to 0.97 with a mean of 0.75); however, the spatial distribution of soil carbon simulated by the ESMs at the 1° scale was not well correlated with the HWSD (Pearson correlation coefficients less than 0.4 and root mean square errors from 9.4 to 20.8 kg C m 2). In northern latitudes where the two data sets overlapped, agreement between the HWSD and the NCSCD was poor (Pearson correlation coefficient 0.33), indicating uncertainty in empirical estimates of soil carbon. We found that a reduced complexity model dependent on NPP and soil temperature explained much of the 1° spatial variation in soil carbon within most ESMs (R2 values between 0.62 and 0.93 for 9 of 11 model centers). However, the same reduced complexity model only explained 10% of the spatial variation in HWSD soil carbon when driven by observations of NPP and temperature, implying that other drivers or processes may be more important in explaining observed soil carbon distributions. The reduced complexity model also showed that differences in simulated soil carbon across ESMs were driven by differences in simulated NPP and the parameterization of soil heterotrophic respiration (inter-model R2 = 0.93), not by structural differences between the models. Overall, our results suggest that despite fair global-scale agreement with observational data and moderate agreement at the biome scale, most ESMs cannot reproduce grid-scale variation in soil carbon and may be missing key processes. Future work should focus on improving the simulation of driving variables for soil carbon stocks and modifying model structures to include additional processes.
Risk Factors for Vitamin D Deficiency among HIV-Infected and Uninfected Injection Drug Users
Allison A. Lambert, M. Bradley Drummond, Shruti H. Mehta, Todd T. Brown, Gregory M. Lucas, Gregory D. Kirk, Michelle M. Estrella
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095802
Abstract: Introduction Vitamin D deficiency is highly prevalent and is associated with bone disease, cardiovascular disease, metabolic syndrome and malignancy. Injection drug users (IDUs), with or without HIV infection, are at risk for these conditions; however, limited data on vitamin D deficiency exist in this population. We determined the prevalence and correlates of vitamin D deficiency among urban IDUs in the AIDS Linked to the IntraVenous Experience (ALIVE) Study cohort. Methods For this cross-sectional sub-study, vitamin D deficiency was defined as a serum 25(OH)-vitamin D level <20 ng/mL. Multivariable logistic regression was used to identify factors independently associated with vitamin D deficiency. Results Of 950 individuals analyzed, 29% were HIV-infected. The median age was 49 years; 65% were male, and 91% were black. The median vitamin D level was 13.5 ng/mL (IQR, 9.0–20.3); 74% were deficient (68% in HIV-infected vs. 76% in HIV-uninfected, p = 0.01). Non-black race, fall/winter season, multivitamin intake, higher serum albumin, HCV seropositivity and HIV-infection were associated with significantly lower odds of vitamin D deficiency. Conclusions Vitamin D deficiency is prevalent among IDUs. Notably, HIV-infected IDUs were less likely to be vitamin D deficient. Higher vitamin D levels were associated with multivitamin intake and with higher albumin levels, suggesting that nutritional status contributes substantially to deficiency. The association between HCV serostatus and vitamin D level remains unclear. Further investigation is needed to define the clinical implications of the heavy burden of vitamin D deficiency in this high-risk, aging population with significant co-morbidities.
Frailty, HIV Infection, and Mortality in an Aging Cohort of Injection Drug Users
Damani A. Piggott, Abimereki D. Muzaale, Shruti H. Mehta, Todd T. Brown, Kushang V. Patel, Sean X. Leng, Gregory D. Kirk
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054910
Abstract: Background Frailty is associated with morbidity and premature mortality among elderly HIV-uninfected adults, but the determinants and consequences of frailty in HIV-infected populations remain unclear. We evaluated the correlates of frailty, and the impact of frailty on mortality in a cohort of aging injection drug users (IDUs). Methods Frailty was assessed using standard criteria among HIV-infected and uninfected IDUs in 6-month intervals from 2005 to 2008. Generalized linear mixed-model analyses assessed correlates of frailty. Cox proportional hazards models estimated risk for all-cause mortality. Results Of 1230 participants at baseline, the median age was 48 years and 29% were HIV-infected; the frailty prevalence was 12.3%. In multivariable analysis of 3,365 frailty measures, HIV-infected IDUs had an increased likelihood of frailty (OR, 1.66; 95% CI, 1.24–2.21) compared to HIV-uninfected IDUs; the association was strongest (OR, 2.37; 95% CI, 1.62–3.48) among HIV-infected IDUs with advanced HIV disease (CD4<350 cells/mm3 and detectable HIV RNA). No significant association was seen with less advanced disease. Sociodemographic factors, comorbidity, depressive symptoms, and prescription drug abuse were also independently associated with frailty. Mortality risk was increased with frailty alone (HR 2.63, 95% CI, 1.23–5.66), HIV infection alone (HR 3.29, 95% CI, 1.85–5.88), and being both HIV-infected and frail (HR, 7.06; 95%CI 3.49–14.3). Conclusion Frailty was strongly associated with advanced HIV disease, but IDUs with well-controlled HIV had a similar prevalence to HIV-uninfected IDUs. Frailty was independently associated with mortality, with a marked increase in mortality risk for IDUs with both frailty and HIV infection.
Historical accounts of the transformation of a prairie town
Todd D. Fagin,Melissa Scott Brown
Oklahoma Native Plant Record , 2003,
Abstract: Prior to European settlement, the area that would later become Norman, Oklahoma was dominated by prairie vegetation. Woody vegetation was limited to riparian zones and isolated groves presumably protected from the effects of fire. The contemporary landscape of Norman, stands in stark contrast to this “treeless” prairie, and is now characterized by a so-called urban forest. In this paper, we analyze a number of archival sources, ranging from early expedition and traveler accounts to postsettlement photography in order to qualitatively assess the nature of the landscape in and around the present-day city of Norman prior to and immediately following European settlement. We also utilize repeat photography to document the floristic and vegetation changes that have occurred. We found that the pre-European settlement landscape was characterized by rolling prairies heavily influenced by the grazing of black-tailed prairie dogs (Cynomys ludovicianus), bison (Bison bison), and pronghorn antelope (Antilocapra americana). Forbs were limited and herbaceous vegetation was dominated primarily by closely grazed grasses. Woody vegetation was limited primarily to watercourses and ravines, though numerous accounts cite thickets of oaks (Quercusspp.) occurring in the adjacent cross timbers. Today, the vegetation of Norman is characterized by the dominance of woody vegetation. Within Norman’s historical residential areas, commonly occurring species include hackberry (Celtis occidentalis), Shumard’s oak (Q. shumardii), silver maple (Acer saccharinum), and sycamore (Platanus occidentalis).
Sleep Disordered Breathing, Fatigue, and Sleepiness in HIV-Infected and -Uninfected Men
Susheel P. Patil, Todd T. Brown, Lisa P. Jacobson, Joseph B. Margolick, Alison Laffan, Lisette Johnson-Hill, Rebecca Godfrey, Jacquett Johnson, Sandra Reynolds, Alan R. Schwartz, Philip L. Smith
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099258
Abstract: Study Objectives We investigated the association of HIV infection and highly active antiretroviral therapy (HAART) with sleep disordered breathing (SDB), fatigue, and sleepiness. Methods HIV-uninfected men (HIV?; n = 60), HIV-infected men using HAART (HIV+/HAART+; n = 58), and HIV-infected men not using HAART (HIV+/HAART?; n = 41) recruited from two sites of the Multicenter AIDS cohort study (MACS) underwent a nocturnal sleep study, anthropometric assessment, and questionnaires for fatigue and the Epworth Sleepiness Scale. The prevalence of SDB in HIV- men was compared to that in men matched from the Sleep Heart Health Study (SHHS). Results The prevalence of SDB was unexpectedly high in all groups: 86.7% for HIV?, 70.7% for HIV+/HAART+, and 73.2% for HIV+/HAART?, despite lower body-mass indices (BMI) in HIV+ groups. The higher prevalence in the HIV? men was significant in univariate analyses but not after adjustment for BMI and other variables. SDB was significantly more common in HIV? men in this study than those in SHHS, and was common in participants with BMIs <25 kg/m2. HIV+ men reported fatigue more frequently than HIV? men (25.5% vs. 6.7%; p = 0.003), but self-reported sleepiness did not differ among the three groups. Sleepiness, but not fatigue, was significantly associated with SDB. Conclusions SDB was highly prevalent in HIV? and HIV+ men, despite a normal or slightly elevated BMI. The high rate of SDB in men who have sex with men deserves further investigation. Sleepiness, but not fatigue, was related to the presence of SDB. Clinicians caring for HIV-infected patients should distinguish between fatigue and sleepiness when considering those at risk for SDB, especially in non-obese men.
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