Publications by authors named "James G Fadel"

22 Publications

  • Page 1 of 1

Inhibited Methanogenesis in the Rumen of Cattle: Microbial Metabolism in Response to Supplemental 3-Nitrooxypropanol and Nitrate.

Front Microbiol 2021 27;12:705613. Epub 2021 Jul 27.

Department of Animal Science, University of California, Davis, Davis, CA, United States.

3-Nitrooxypropanol (3-NOP) supplementation to cattle diets mitigates enteric CH emissions and may also be economically beneficial at farm level. However, the wider rumen metabolic response to methanogenic inhibition by 3-NOP and the intermediary metabolite requires further exploration. Furthermore, supplementation potently decreases CH emissions from cattle. The reduction of utilizes H and yields , the latter of which may also inhibit rumen methanogens, although a different mode of action than for 3-NOP and its derivative was hypothesized. Our objective was to explore potential responses of the fermentative and methanogenic metabolism in the rumen to 3-NOP, and their metabolic derivatives using a dynamic mechanistic modeling approach. An extant mechanistic rumen fermentation model with state variables for carbohydrate substrates, bacteria and protozoa, gaseous and dissolved fermentation end products and methanogens was extended with a state variable of either 3-NOP or . Both new models were further extended with a state variable, with exerting methanogenic inhibition, although the modes of action of 3-NOP-derived and -derived are different. Feed composition and intake rate (twice daily feeding regime), and supplement inclusion were used as model inputs. Model parameters were estimated to experimental data collected from the literature. The extended 3-NOP and models both predicted a marked peak in H emission shortly after feeding, the magnitude of which increased with higher doses of supplement inclusion. The H emission rate appeared positively related to decreased acetate proportions and increased propionate and butyrate proportions. A decreased CH emission rate was associated with 3-NOP and supplementation. Omission of the state variable from the 3-NOP model did not change the overall dynamics of H and CH emission and other metabolites. However, omitting the state variable from the model did substantially change the dynamics of H and CH emissions indicated by a decrease in both H and CH emission after feeding. Simulations do not point to a strong relationship between methanogenic inhibition and the rate of and formation upon 3-NOP supplementation, whereas the metabolic response to supplementation may largely depend on methanogenic inhibition by .
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http://dx.doi.org/10.3389/fmicb.2021.705613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353594PMC
July 2021

Bayesian mechanistic modeling of thermodynamically controlled volatile fatty acid, hydrogen and methane production in the bovine rumen.

J Theor Biol 2019 11 8;480:150-165. Epub 2019 Aug 8.

Animal Nutrition Group, Wageningen University & Research, PO Box 338, 6700 AH, Wageningen, the Netherlands.

Dynamic modeling of mechanisms driving volatile fatty acid and hydrogen production in the rumen microbial ecosystem contributes to the heuristic prediction of CH emissions from dairy cattle into the environment. Existing mathematical rumen models, however, lack the representation of these mechanisms. A dynamic mechanistic model was developed that simulates the thermodynamic control of hydrogen partial pressure ( [Formula: see text] ) on volatile fatty acid (VFA) fermentation pathways via the NAD to NADH ratio in fermentative microbes, and methanogenesis in the bovine rumen. This model is unique and closely aligns with principles of reaction kinetics and thermodynamics. Model state variables represent ruminal carbohydrate substrates, bacteria and protozoa, methanogens, and gaseous and dissolved fermentation end products. The model was extended with static equations to model the hindgut metabolism. Feed composition and twice daily feeding were used as model inputs. Model parameters were estimated to experimental data using a Bayesian calibration procedure, after which the uncertainty of the parameter distribution on the model output was assessed. The model predicted a marked peak in [Formula: see text] after feeding that rapidly declined in time. This peak in [Formula: see text] caused a decrease in NAD to NADH ratio followed by an increased propionate molar proportion at the expense of acetate molar proportion, and an increase in CH production that steadily decreased in time, although the magnitude of increase for CH emission was less than for [Formula: see text] . A global sensitivity analysis indicated that parameters that determine the fractional passage rate and NADH oxidation rate altogether explained 86% of the variation in predicted daily CH emission. Model evaluation indicated over-prediction of in vivo CH emissions shortly after feeding, whereas under-prediction was indicated at later times. The present rumen fermentation modeling effort uniquely provides the integration of the [Formula: see text] controlled NAD to NADH ratio for dynamically predicting metabolic pathways that yield VFA, H and CH.
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http://dx.doi.org/10.1016/j.jtbi.2019.08.008DOI Listing
November 2019

Optimizing accuracy of protocols for measuring dry matter and nutrient yield of forage crops.

Sci Total Environ 2018 May 14;624:180-188. Epub 2017 Dec 14.

Department of Animal Science, One Shields Avenue, University of California, Davis, CA 95616, USA. Electronic address:

Farmers around the world must precisely manage nutrients applied to and removed from crop fields to maintain production and without causing nutrient pollution. This study is the first to quantify the baseline accuracy of current industry measurement protocols and achievable accuracy from intensifying protocols for measuring dry matter (DM), nitrogen (N), potassium (K), and phosphorus (P) yields from forage crops harvested for silage. The 'true' DM and nutrient yields of three fields each of corn, sorghum, and small grain were intensively measured by weighing and sampling every truckload of harvested forage. Simulations quantified the accuracy of practical sampling protocols by repeatedly subsampling the complete dataset for each field to measure average truckload weight and average DM and nutrient concentrations. Then uncertainty was propagated to DM, N, P, and K yield calculations using standard error equations. Yields measured using current industry protocols diverged from the true yields of some fields by more than ±40%, emphasizing the need for improved protocols. This study shows that improving average DM and nutrient concentration measurements is unlikely to improve accuracy of yield measurements if average load weight is not precisely measured. Accuracy did not come within 27% of true yields without weighing all truckloads on some fields even when DM and nutrient concentration measurements were perfectly accurate. Once all truckloads were weighed, the timing of forage sample collection to measure average DM concentration had the greatest impact on accuracy; precision improved by an average of 6.2% when >3 samples were evenly spaced throughout the harvest compared to the same number of consecutive samples. All crop fields are affected by within field variation in growing conditions that results in heterogeneity in DM and nutrient yield. Globally, this study provides foundational methodology to quantitatively evaluate and improve yield measurement protocols that ultimately support sustainable crop production.
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http://dx.doi.org/10.1016/j.scitotenv.2017.11.203DOI Listing
May 2018

Development of growth rate, body lipid, moisture, and energy models for white sturgeon () fed at various feeding rates.

Anim Nutr 2017 Mar 9;3(1):46-60. Epub 2016 Nov 9.

Department of Animal Science, University of California, One Shields Avenue, Davis, CA 95616, USA.

The objectives were to develop and evaluate: 1) growth rate models, 2) body lipid, moisture, and energy models for white sturgeon fed at various feeding rates (FR; % body weight [BW] per day) and then evaluate responses at proportions of optimum feeding rate (OFR) across increasing BW (g). For objective 1, 19 datasets from the literature containing initial BW, FR and specific growth rate (SGR; % BW increase per day) were used. For objective 2, 12 datasets from the literature (11 from objective 1) containing SGR, FR, final BW, body lipid (%), protein (%), ash (%), moisture (%), and energy (kJ/g) were used. The average rearing temperatures was 19.2 ± 1.5 °C (mean ± SD). The average nutrient compositions and gross energy of the diets were 45.7 ± 4.3% protein, 14.8 ± 3.2% lipid, and 20.4 ± 1.3 kJ/g, respectively. The logistic model was used for objectives 1 and 2 to develop a statistical relationship between SGR and FR, then an iterative technique was used to estimate OFR for each dataset. For objective 2, the statistical relationship between body lipid, energy, and moisture and FR was established. Using the OFR estimate, SGR, body lipid, energy and moisture were computed at various FR as a proportion of OFR. Finally, a nonparametric fitting procedure was used to establish relationships between SGR, body lipid, energy and moisture (responses) compared with BW (predictor) at various proportions of OFR. This allows visualization of the effect of under- or over-feeding on the various responses. When examining the differences between OFR at 100% and various proportions of OFR, SGR differences decrease and moisture differences increase as BW increases. Lipid and energy differences decrease as BW increases. To our knowledge, these are the first description of changes in nutrient compositions when white sturgeon are fed at various FR. Because physiological and behavioral properties that are unique to sturgeon, results from this study are specific to sturgeon under the conditions of this study and cannot be compared directly with salmonids even if some of the results are similar. This research provides insight to designing future nutritional studies in sturgeon.
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http://dx.doi.org/10.1016/j.aninu.2016.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941066PMC
March 2017

Resequencing and annotation of the Nostoc punctiforme ATTC 29133 genome: facilitating biofuel and high-value chemical production.

AMB Express 2017 Dec 16;7(1):42. Epub 2017 Feb 16.

Department of Animal Science, University of California, Davis, 2251 Meyer Hall, Davis, CA, 95616, USA.

Cyanobacteria have the potential to produce bulk and fine chemicals and members belonging to Nostoc sp. have received particular attention due to their relatively fast growth rate and the relative ease with which they can be harvested. Nostoc punctiforme is an aerobic, motile, Gram-negative, filamentous cyanobacterium that has been studied intensively to enhance our understanding of microbial carbon and nitrogen fixation. The genome of the type strain N. punctiforme ATCC 29133 was sequenced in 2001 and the scientific community has used these genome data extensively since then. Advances in bioinformatics tools for sequence annotation and the importance of this organism prompted us to resequence and reanalyze its genome and to make both, the initial and improved annotation, available to the scientific community. The new draft genome has a total size of 9.1 Mbp and consists of 65 contiguous pieces of DNA with a GC content of 41.38% and 7664 protein-coding genes. Furthermore, the resequenced genome is slightly (5152 bp) larger and contains 987 more genes with functional prediction when compared to the previously published version. We deposited the annotation of both genomes in the Department of Energy's IMG database to facilitate easy genome exploration by the scientific community without the need of in-depth bioinformatics skills. We expect that an facilitated access and ability to search the N. punctiforme ATCC 29133 for genes of interest will significantly facilitate metabolic engineering and genome prospecting efforts and ultimately the synthesis of biofuels and natural products from this keystone organism and closely related cyanobacteria.
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http://dx.doi.org/10.1186/s13568-017-0338-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313495PMC
December 2017

Thermodynamic Driving Force of Hydrogen on Rumen Microbial Metabolism: A Theoretical Investigation.

PLoS One 2016 26;11(10):e0161362. Epub 2016 Oct 26.

Animal Nutrition Group, Wageningen University, Wageningen, The Netherlands.

Hydrogen is a key product of rumen fermentation and has been suggested to thermodynamically control the production of the various volatile fatty acids (VFA). Previous studies, however, have not accounted for the fact that only thermodynamic near-equilibrium conditions control the magnitude of reaction rate. Furthermore, the role of NAD, which is affected by hydrogen partial pressure (PH2), has often not been considered. The aim of this study was to quantify the control of PH2 on reaction rates of specific fermentation pathways, methanogenesis and NADH oxidation in rumen microbes. The control of PH2 was quantified using the thermodynamic potential factor (FT), which is a dimensionless factor that corrects a predicted kinetic reaction rate for the thermodynamic control exerted. Unity FT was calculated for all glucose fermentation pathways considered, indicating no inhibition of PH2 on the production of a specific type of VFA (e.g., acetate, propionate and butyrate) in the rumen. For NADH oxidation without ferredoxin oxidation, increasing PH2 within the rumen physiological range decreased FT from unity to zero for different NAD+ to NADH ratios and pH of 6.2 and 7.0, which indicates thermodynamic control of PH2. For NADH oxidation with ferredoxin oxidation, increasing PH2 within the rumen physiological range decreased FT from unity at pH of 7.0 only. For the acetate to propionate conversion, FT increased from 0.65 to unity with increasing PH2, which indicates thermodynamic control. For propionate to acetate and butyrate to acetate conversions, FT decreased to zero below the rumen range of PH2, indicating full thermodynamic suppression. For methanogenesis by archaea without cytochromes, FT differed from unity only below the rumen range of PH2, indicating no thermodynamic control. This theoretical investigation shows that thermodynamic control of PH2 on individual VFA produced and associated yield of hydrogen and methane cannot be explained without considering NADH oxidation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161362PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081179PMC
June 2017

Effects of feed restriction on salinity tolerance in white sturgeon (Acipenser transmontanus).

Comp Biochem Physiol A Mol Integr Physiol 2015 Oct 27;188:156-67. Epub 2015 Jun 27.

Department of Animal Science, University of California, Davis, CA 95616, USA. Electronic address:

A multistressor study was conducted to investigate interactive effects of nutritional status and salinity on osmoregulation of juvenile white sturgeon. Our hypothesis was that lower nutritional status would decrease the salinity tolerance of juvenile white sturgeon. A four-week feed restriction (12.5%, 25%, 50%, 100% of optimum feeding rate: OFR defined as the rate (% body weight per day) at which growth is maximal) trial was performed, and relevant indices of nutritional status were measured. Following the trial, sturgeon were acutely exposed to various salinities (0, 8, 16, 24 ppt) for 120 h, and relevant osmoregulatory measurements were made at 12, 72, and 120 h post-salinity exposures. The feed-restriction trial resulted in a graded nutritional response with the most feed-restricted group (12.5% OFR) showing the lowest nutritional status. The salinity exposure trial showed clear evidence that lower nutritional status decreased the salinity tolerance of juvenile white sturgeon. Increasing salinities resulted in significant alterations in osmoregulatory indices of all feeding groups; however, a significantly slower acclimatory response to 24 ppt was detected in the most feed-restricted group compared to the non-feed-restricted group (100% OFR). Furthermore, evaluation of the effect of nutritional status on the relationship between osmoregulatory measurements and body size showed that there was a significant negative relationship between osmoregulatory performance and body size within the most feed-restricted group. This suggests that there is a certain body size range (200-300 g based on our finding) where juvenile white sturgeon can maximize osmoregulatory capacity at a salinity of 24 ppt.
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http://dx.doi.org/10.1016/j.cbpa.2015.06.027DOI Listing
October 2015

Impact of nutrition and salinity changes on biological performances of green and white sturgeon.

PLoS One 2015 1;10(4):e0122029. Epub 2015 Apr 1.

Department of Wildlife, Fish and Conservation Biology, University of California Davis, Davis, California, United States of America.

Green and white sturgeon are species of high conservational and economic interest, particularly in the San Francisco Bay Delta (SFBD) for which significant climate change-derived alterations in salinity and nutritional patterns are forecasted. Although there is paucity of information, it is critical to test the network of biological responses underlying the capacity of animals to tolerate current environmental changes. Through nutrition and salinity challenges, climate change will likely have more physiological effect on young sturgeon stages, which in turn may affect growth performance. In this study, the two species were challenged in a multiple-factor experimental setting, first to levels of feeding rate, and then to salinity levels for different time periods. Data analysis included generalized additive models to select predictors of growth performance (measured by condition factor) among the environmental stressors considered and a suite of physiological variables. Using structural equation modeling, a path diagram is proposed to quantify the main linkages among nutrition status, salinity, osmoregulation variables, and growth performances. Three major trends were anticipated for the growth performance of green and white sturgeon in the juvenile stage in the SFBD: (i) a decrease in prey abundance will be highly detrimental for the growth of both species; (ii) an acute increase in salinity within the limits studied can be tolerated by both species but possibly the energy spent in osmoregulation may affect green sturgeon growth within the time window assessed; (iii) the mechanism of synergistic effects of nutrition and salinity changes will be more complex in green sturgeon, with condition factor responding nonlinearly to interactions of salinity and nutrition status or time of salinity exposure. Green sturgeon merits special scientific attention and conservation effort to offset the effects of feed restriction and salinity as key environmental stressors in the SFBD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122029PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382339PMC
April 2016

Effect of nutritional status on the osmoregulation of green sturgeon (Acipenser medirostris).

Physiol Biochem Zool 2015 Jan-Feb;88(1):22-42. Epub 2014 Dec 18.

Department of Animal Science, University of California, Davis, California 95616; 2Department of Marine Biomaterials and Aquaculture, Feeds and Foods Nutrition Research Center, Pukyong National University, Busan, Korea; 3School of Natural and Social Sciences, Purchase College, State University of New York, Purchase, New York 10577; 4Department of Wildlife, Fish, and Conservation Biology, University of California, Davis, California 95616.

Anthropogenic climate change is linked to food web and salinity fluctuations in estuarine environments. Both decreased nutritional status and environmental salinity influence the physiological tolerance and health of fish populations; however, limited information on the interaction of these two factors and their physiological consequences is available. The green sturgeon (Acipenser medirostris) is a species of special concern in California, and the southern distinct population segment is listed as threatened. To test the hypothesis that poor nutrition negatively affects osmoregulation, juvenile green sturgeon (222 d posthatch) were randomly assigned to four feed restriction groups (12.5%, 25%, 50%, and 100% of the optimal feeding rate for 4 wk). Fish were then acutely exposed to 0-, 8-, 16-, or 32-ppt salinities and sampled at three time points (12, 72, or 120 h). Feed restriction significantly (P < 0.05) decreased specific growth rate, feed efficiency, condition factor, whole-body lipids, and protein content as well as plasma glucose, triglycerides, and proteins. Furthermore, feed restriction, salinity concentration, and salinity exposure time had significant effects on hematological indexes (hematocrit, hemoglobin), plasma values (osmolality, Na(+), K(+), Cl(-), glucose, lactate, cortisol), enzymatic activity (gill and pyloric ceca Na(+)/K(+) ATPase), and morphology of gill mitochondria-rich cells. The largest disturbances were observed at the highest salinity treatments across all feeding regimes. In addition, the interaction between feed restriction and acute salinity exposure at the highest salinity treatment resulted in high mortality rates during the first 72 h of salinity exposure. Evaluating the interactions of these environmental stressors and their implications on green sturgeon physiological tolerance will inform restoration and management efforts in rapidly changing estuarine environments.
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http://dx.doi.org/10.1086/679519DOI Listing
September 2015

Prediction of enteric methane emissions from cattle.

Glob Chang Biol 2014 Jul 25;20(7):2140-8. Epub 2014 Apr 25.

Department of Animal Science, University of California, Davis, CA, 95616, USA.

Agriculture has a key role in food production worldwide and it is a major component of the gross domestic product of several countries. Livestock production is essential for the generation of high quality protein foods and the delivery of foods in regions where animal products are the main food source. Environmental impacts of livestock production have been examined for decades, but recently emission of methane from enteric fermentation has been targeted as a substantial greenhouse gas source. The quantification of methane emissions from livestock on a global scale relies on prediction models because measurements require specialized equipment and may be expensive. The predictive ability of current methane emission models remains poor. Moreover, the availability of information on livestock production systems has increased substantially over the years enabling the development of more detailed methane prediction models. In this study, we have developed and evaluated prediction models based on a large database of enteric methane emissions from North American dairy and beef cattle. Most probable models of various complexity levels were identified using a Bayesian model selection procedure and were fitted under a hierarchical setting. Energy intake, dietary fiber and lipid proportions, animal body weight and milk fat proportion were identified as key explanatory variables for predicting emissions. Models here developed substantially outperformed models currently used in national greenhouse gas inventories. Additionally, estimates of repeatability of methane emissions were lower than the ones from the literature and multicollinearity diagnostics suggested that prediction models are stable. In this context, we propose various enteric methane prediction models which require different levels of information availability and can be readily implemented in national greenhouse gas inventories of different complexity levels. The utilization of such models may reduce errors associated with prediction of methane and allow a better examination and representation of policies regulating emissions from cattle.
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http://dx.doi.org/10.1111/gcb.12471DOI Listing
July 2014

The interactive effects of selenomethionine and methylmercury on their absorption, disposition, and elimination in juvenile white sturgeon.

Aquat Toxicol 2013 Jan 28;126:274-82. Epub 2012 Sep 28.

Department of Animal Science, University of California, Davis 95616, USA.

Selenium (Se) and mercury (Hg) are prevalent pollutants of industrialized watersheds. However, when co-administered, Se has protective effects on organisms from Hg. The mechanism is not fully understood, but it is thought that Se reduces Hg availability, either by forming biologically inert complexes and/or associating with selenoproteins. Despite concerns with aquatic contaminations, relatively little information is available on the interaction in aquatic organisms. In the present study, the interactive effects of Se and Hg on their absorption, disposition, and elimination were examined in juvenile white sturgeon, a benthic fish species at high risk to exposures of both contaminants. Selenium and Hg were provided as L-selenomethionine (SeMet) and methylmercury (MeHg), respectively. Groups of 10 sturgeon were orally intubated with a single dose of either 0 (control), SeMet (500 μg Se/kg body weight; BW), MeHg (850 μg Hg/kg BW), or their combination (Se/Hg; 500 μg Se/kg and 850 μg Hg/kg BW). The blood was repeatedly sampled and urine collected from the fish, over a 48 h post intubation period. At 48 h, the fish were sacrificed for Se and Hg tissue concentration and distribution. The co-administration of SeMet and MeHg significantly (p<0.05) lowered blood concentrations of both Se and Hg and tissue Se concentrations. Similarly, assimilation of Se and Hg was also reduced significantly. The interaction has a more quantitative effect on Se metabolism because the reduction in the overall tissue Se is a consequence of reduced Se absorption at the gut and not from the metabolic effects after absorption. In contrast, given the pulse increase in blood Hg concentration, tissue redistribution, and increased urinary elimination, the interactive effect on tissue Hg concentration is likely to be post-absorption. Even in the absence of exogenous SeMet, Se and Hg co-accumulated in tissue at a Se:Hg molar ratio greater than 1. Thus, similar to mammals, maintaining at least a 1:1 molar ratio of Se and Hg is of great physiological importance in the white sturgeon. Interestingly, SeMet did not divert Hg from the brain. Allocation of Se from the kidneys may have occurred in order to maintain the high Se:Hg molar ratios in the brain of white sturgeon. In the current study, the combined use of kinetic analysis and that of the conventional approach of measuring tissue concentration changes provided a comprehensive understanding of the interactive effect of SeMet and MeHg on their respective metabolic processes in juvenile white sturgeon.
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http://dx.doi.org/10.1016/j.aquatox.2012.09.018DOI Listing
January 2013

This kinetic, bioavailability, and metabolism study of RRR-α-tocopherol in healthy adults suggests lower intake requirements than previous estimates.

J Nutr 2012 Dec 17;142(12):2105-11. Epub 2012 Oct 17.

Food Components and Health Laboratory, USDA, Beltsville, MD, USA.

Kinetic models enable nutrient needs and kinetic behaviors to be quantified and provide mechanistic insights into metabolism. Therefore, we modeled and quantified the kinetics, bioavailability, and metabolism of RRR-α-tocopherol in 12 healthy adults. Six men and 6 women, aged 27 ± 6 y, each ingested 1.81 nmol of [5(-14)CH(3)]-(2R, 4'R, 8'R)-α-tocopherol; each dose had 3.70 kBq of (14)C. Complete collections of urine and feces were made over the first 21 d from dosing. Serial blood samples were drawn over the first 70 d from dosing. All specimens were analyzed for RRR-α-tocopherol. Specimens were also analyzed for (14)C using accelerator MS. From these data, we modeled and quantified the kinetics of RRR-α-tocopherol in vivo in humans. The model had 11 compartments, 3 delay compartments, and reservoirs for urine and feces. Bioavailability of RRR-α-tocopherol was 81 ± 1%. The model estimated residence time and half-life of the slowest turning-over compartment of α-tocopherol (adipose tissue) at 499 ± 702 d and 184 ± 48 d, respectively. The total body store of RRR-α-tocopherol was 25,900 ± 6=220 μmol (11 ± 3 g) and we calculated the adipose tissue level to be 1.53 μmol/g (657 μg/g). We found that a daily intake of 9.2 μmol (4 mg) of RRR-α-tocopherol maintained plasma RRR-α-tocopherol concentrations at 23 μmol/L. These findings suggest that the dietary requirement for vitamin E may be less than that currently recommended and these results will be important for future updates of intake recommendations.
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http://dx.doi.org/10.3945/jn.112.166462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497961PMC
December 2012

Gender and single nucleotide polymorphisms in MTHFR, BHMT, SPTLC1, CRBP2, CETP, and SCARB1 are significant predictors of plasma homocysteine normalized by RBC folate in healthy adults.

J Nutr 2012 Sep 25;142(9):1764-71. Epub 2012 Jul 25.

Department of Nutrition, University of California, Davis, CA, USA.

Using linear regression models, we studied the main and 2-way interaction effects of the predictor variables gender, age, BMI, and 64 folate/vitamin B-12/homocysteine (Hcy)/lipid/cholesterol-related single nucleotide polymorphisms (SNP) on log-transformed plasma Hcy normalized by RBC folate measurements (nHcy) in 373 healthy Caucasian adults (50% women). Variable selection was conducted by stepwise Akaike information criterion or least angle regression and both methods led to the same final model. Significant predictors (where P values were adjusted for false discovery rate) included type of blood sample [whole blood (WB) vs. plasma-depleted WB; P < 0.001] used for folate analysis, gender (P < 0.001), and SNP in genes SPTLC1 (rs11790991; P = 0.040), CRBP2 (rs2118981; P < 0.001), BHMT (rs3733890; P = 0.019), and CETP (rs5882; P = 0.017). Significant 2-way interaction effects included gender × MTHFR (rs1801131; P = 0.012), gender × CRBP2 (rs2118981; P = 0.011), and gender × SCARB1 (rs83882; P = 0.003). The relation of nHcy concentrations with the significant SNP (SPTLC1, BHMT, CETP, CRBP2, MTHFR, and SCARB1) is of interest, especially because we surveyed the main and interaction effects in healthy adults, but it is an important area for future study. As discussed, understanding Hcy and genetic regulation is important, because Hcy may be related to inflammation, obesity, cardiovascular disease, and diabetes mellitus. We conclude that gender and SNP significantly affect nHcy.
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http://dx.doi.org/10.3945/jn.112.160333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417835PMC
September 2012

Absorption, distribution, and elimination of graded oral doses of methylmercury in juvenile white sturgeon.

Aquat Toxicol 2012 Oct 26;122-123:163-71. Epub 2012 Jun 26.

Department of Animal Science, University of California, Davis, CA 95616, USA.

Mercury (Hg) is toxic and is released into the environment from a wide variety of anthropogenic sources. Methylmercury (MeHg), a product of microbial methylation, enables rapid Hg bioaccumulation and biomagnification in the biota. Methylmercury is sequestered and made available to the rest of the biota through the benthic-detrital component leading to the high risk of exposure to benthic fish species, such as white sturgeon (Acipenser transmontanus). In the present study, a combined technique of stomach intubation, dorsal aorta cannulation, and urinary catheterization was utilized to characterize the absorption, distribution, and elimination of Hg in white sturgeon over a 48h exposure. Mercury, as methylmercury chloride, at either 0, 250, 500, or 1000 μg Hg/kg body weight, was orally intubated into white sturgeon, in groups of five. The blood was repeatedly sampled and urine collected from the fish over the 48h post intubation period, and at 48h, the fish were sacrificed for Hg tissue concentration and distribution determinations. The fractional rate of absorption (K), blood Hg concentration (μg/ml), tissue concentration (μg/g dry weight) and distribution (%), and urinary Hg elimination flux (μg/kg/h) are significantly different (p<0.05) among the MeHg doses. Complete blood uptake of Hg was observed in all MeHg treated fish by 12h. The maximal observed blood Hg concentration peaks are 0.56±0.02, 0.70±0.02, and 2.19±0.07 μg/ml (mean±SEM) for the 250, 500, and 1000 μgHg/kg body weight dose groups, respectively. Changes in blood Hg profiles can be described by a monomolecular function in all of the MeHg treated fish. The Hg concentration asymptote (A) and K are dose dependent. The relationship between A and the intubation dose, however, is nonlinear. Mercury levels in certain tissues are comparable to field data and longer-term study, indicating that the lower doses used in the current study are ecologically relevant for the species. Tissue Hg concentrations are in the following decreasing order: gastro-intestinal tract>kidney>spleen>gill>heart>liver>brain>white muscle and remaining whole body. At 48h, Hg was found to be preferentially distributed to metabolically active tissues. Digestibility is highest at the lowest MeHg dose. Measurable urinary Hg was observed in the fish treated with the highest MeHg dose, and a significant increase in the elimination flux was observed between 3 and 12h post intubation.
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http://dx.doi.org/10.1016/j.aquatox.2012.06.003DOI Listing
October 2012

Selenocompounds in juvenile white sturgeon: evaluating blood, tissue, and urine selenium concentrations after a single oral dose.

Aquat Toxicol 2012 Mar 16;109:158-65. Epub 2011 Dec 16.

Department of Animal Science, University of California, Davis, CA, USA.

Selenium (Se) is an essential micronutrient for all vertebrates, however, at environmental relevant levels, it is a potent toxin. In the San Francisco Bay-Delta, white sturgeon, an ancient Chondrostean fish of high ecological and economic value, is at risk to Se exposure. The present study is the first to examine the uptake, distribution, and excretion of various selenocompounds in white sturgeon. A combined technique of stomach intubation, dorsal aorta cannulation, and urinary catheterization was utilized, in this study, to characterize the short-term effects of Se in the forms of sodium-selenate (Selenate), sodium-selenite (Selenite), selenocystine (SeCys), l-selenomethionine (SeMet), Se-methylseleno-l-cysteine (MSeCys), and selenoyeast (SeYeast). An ecologically relevant dose of Se (∼500 μg/kg body weight) was intubated into groups of 5 juvenile white sturgeon. Blood and urine samples were repeatedly collected over the 48 h post intubation period and fish were sacrificed for Se tissue concentration and distribution at 48 h. The tissue concentration and distribution, blood concentrations, and urinary elimination of Se significantly differ (p ≤ 0.05) among forms. In general, organic selenocompounds maintain higher blood concentrations, with SeMeCys maintaining the highest area under the curve (66.3 ± 8.7 and 9.3 ± 1.0 μg h/ml) and maximum Se concentration in blood (2.3 ± 0.2 and 0.4 ± 0.2 μg/ml) in both the protein and non-protein bound fractions, respectively. Selenate, however, did not result in significant increase of Se concentration, compared with the control, in the protein-bound blood fraction. Regardless of source, Se is preferentially distributed into metabolically active tissues, with the SeMet treated fish achieving the highest concentration in most tissues. In contrast, Selenite has very similar blood concentrations and tissue distribution profile to SeCys and SeYeast. From blood and tissue Se concentrations, Selenate is not stored in blood, but taken up rapidly by the liver and white muscle. Urinary elimination of Se is form dependent and peaks between 3 and 12 h post intubation. A basic understanding of the overall Se absorption, distribution, and elimination is provided through monitoring tissue Se concentrations, however, conclusions regarding to the dynamics and the specific processes of Se metabolism can only be inferred, in the absence of kinetic information.
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http://dx.doi.org/10.1016/j.aquatox.2011.12.009DOI Listing
March 2012

Selenocompounds in juvenile white sturgeon: estimating absorption, disposition, and elimination of selenium using Bayesian hierarchical modeling.

Aquat Toxicol 2012 Mar 22;109:150-7. Epub 2011 Nov 22.

Department of Animal Science, University of California, Davis, CA 95616, USA.

The biological function of selenium (Se) is determined by its form and concentration. Selenium is an essential micronutrient for all vertebrates, however, at environmental levels, it is a potent toxin. In the San Francisco Bay-Delta, Se pollution threatens top predatory fish, including white sturgeon. A multi-compartmental Bayesian hierarchical model was developed to estimate the fractional rates of absorption, disposition, and elimination of selenocompounds, in white sturgeon, from tissue measurements obtained in a previous study (Huang et al., 2012). This modeling methodology allows for a population based approach to estimate kinetic physiological parameters in white sturgeon. Briefly, thirty juvenile white sturgeon (five per treatment) were orally intubated with a control (no selenium) or a single dose of Se (500 μg Se/kg body weight) in the form of one inorganic (Selenite) or four organic selenocompounds: selenocystine (SeCys), l-selenomethionine (SeMet), Se-methylseleno-l-cysteine (MSeCys), or selenoyeast (SeYeast). Blood and urine Se were measured at intervals throughout the 48h post intubation period and eight tissues were sampled at 48 h. The model is composed of four state variables, conceptually the gut (Q1), blood (Q2), and tissue (Q3); and urine (Q0), all in units of μg Se. Six kinetics parameters were estimated: the fractional rates [1/h] of absorption, tissue disposition, tissue release, and urinary elimination (k12, k23, k32, and k20), the proportion of the absorbed dose eliminated through the urine (f20), and the distribution blood volume (V; percent body weight, BW). The parameter k12 was higher in sturgeon given the organic Se forms, in the descending order of MSeCys > SeMet > SeCys > Selenite > SeYeast. The parameters k23 and k32 followed similar patterns, and f20 was lowest in fish given MSeCys. Selenium form did not affect k20 or V. The parameter differences observed can be attributed to the different mechanisms of transmucosal transport, metabolic reduction, and storage of the Se forms, which, in general, appear to be similar to that in mammals. We have demonstrated that the Bayesian approach is a powerful tool for integrating quantitative information from a study with sparse blood and urinary measurements and tissue concentrations from a single time point, while providing a full characterization of parameter variability. The model permits the quantitative mechanistic interpretation and predictions of Se absorption, disposition, and elimination processes. Furthermore, the model represents a first step towards population based physiological toxicokinetic modeling of Se in white sturgeon.
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http://dx.doi.org/10.1016/j.aquatox.2011.11.005DOI Listing
March 2012

Comparison of acrylamide intake from Western and guideline based diets using probabilistic techniques and linear programming.

Food Chem Toxicol 2012 Mar 15;50(3-4):877-83. Epub 2011 Nov 15.

University of California, Department of Food Science and Technology, One Shields Avenue, Davis, CA 95616, United States.

Western and guideline based diets were compared to determine if dietary improvements resulting from following dietary guidelines reduce acrylamide intake. Acrylamide forms in heat treated foods and is a human neurotoxin and animal carcinogen. Acrylamide intake from the Western diet was estimated with probabilistic techniques using teenage (13-19 years) National Health and Nutrition Examination Survey (NHANES) food consumption estimates combined with FDA data on the levels of acrylamide in a large number of foods. Guideline based diets were derived from NHANES data using linear programming techniques to comport to recommendations from the Dietary Guidelines for Americans, 2005. Whereas the guideline based diets were more properly balanced and rich in consumption of fruits, vegetables, and other dietary components than the Western diets, acrylamide intake (mean±SE) was significantly greater (P<0.001) from consumption of the guideline based diets (0.508±0.003 μg/kg/day) than from consumption of the Western diets (0.441±0.003 μg/kg/day). Guideline based diets contained less acrylamide contributed by French fries and potato chips than Western diets. Overall acrylamide intake, however, was higher in guideline based diets as a result of more frequent breakfast cereal intake. This is believed to be the first example of a risk assessment that combines probabilistic techniques with linear programming and results demonstrate that linear programming techniques can be used to model specific diets for the assessment of toxicological and nutritional dietary components.
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http://dx.doi.org/10.1016/j.fct.2011.11.006DOI Listing
March 2012

Quantitation of [5-14CH3]-(2R, 4'R, 8'R)-α-tocopherol in humans.

J Nutr 2011 Aug 29;141(8):1482-8. Epub 2011 Jun 29.

Department of Nutrition, University of California, Davis, CA 95616, USA.

Half-lives of α-tocopherol in plasma have been reported as 2-3 d, whereas the Elgin Study required >2 y to deplete α-tocopherol, so gaps exist in our quantitative understanding of human α-tocopherol metabolism. Therefore, 6 men and 6 women aged 27 ± 6 y (mean ± SD) ingested 1.81 nmol, 3.70 kBq of [5-(14)CH(3)]-(2R, 4'R, 8'R)-α-tocopherol. The levels of (14)C in blood plasma and washed RBC were monitored frequently from 0 to 460 d while the levels of (14)C in urine and feces were monitored from 0 to 21 d. Total fecal elimination (fecal + metabolic fecal) was 23.24 ± 5.81% of the (14)C dose, so feces over urine was the major route of elimination of the ingested [5-(14)CH(3)]-(2R, 4'R, 8'R)-α-tocopherol, consistent with prior estimates. The half-life of α-tocopherol varied in plasma and RBC according to the duration of study. The minute dose coupled with frequent monitoring over 460 d and 21 d for blood, urine, and feces ensured the [5-(14)CH(3)]-(2R, 4'R, 8'R)-α-tocopherol (the tracer) had the chance to fully mix with the endogenous [5-(14)CH(3)]-(2R, 4'R, 8'R)-α-tocopherol (the tracee). The (14)C levels in neither plasma nor RBC had returned to baseline by d 460, indicating that the t(1/2) of [5-CH(3)]-(2R, 4'R, 8'R)-α-tocopherol in human blood was longer than prior estimates.
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http://dx.doi.org/10.3945/jn.111.138925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138640PMC
August 2011

Volatile organic compound emissions from dairy cows and their waste as measured by proton-transfer-reaction mass spectrometry.

Environ Sci Technol 2007 Feb;41(4):1310-6

Department of Environmental Science, Policy, and Management, University of California, Berkeley, Hilgard Hall, Berkeley, California 94720, USA.

California dairies house approximately 1.8 million lactating and 1.5 million dry cows and heifers. State air regulatory agencies view these dairies as a major air pollutant source, but emissions data are sparse, particularly for volatile organic compounds (VOCs). The objective of this work was to determine VOC emissions from lactating and dry dairy cows and their waste using an environmental chamber. Carbon dioxide and methane were measured to provide context for the VOCs. VOCs were measured by proton-transfer-reaction mass spectrometry (PTR-MS). The compounds with highest fluxes when cows plus waste were present were methanol, acetone + propanal, dimethylsulfide, and m/z 109 (likely 4-methyl-phenol). The compounds with highest fluxes from fresh waste (urine and feces) were methanol, m/z 109, and m/z 60 (likely trimethylamine). Ethanol fluxes are reported qualitatively, and several VOCs that were likely emitted (formaldehyde, methylamine, dimethylamine) were not detectable by PTR-MS. The sum of reactive VOC fluxes measured when cows were present was a factor of 6-10 less than estimates historically used for regulatory purposes. In addition, ozone formation potentials of the dominant VOCs were -10% those of typical combustion or biogenic VOCs. Thus dairy cattle have a comparatively small impact on ozone formation per VOC mass emitted.
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http://dx.doi.org/10.1021/es061475eDOI Listing
February 2007

A feasibility study quantifying in vivo human alpha-tocopherol metabolism.

Am J Clin Nutr 2006 Dec;84(6):1430-41

Department of Nutrition, University of California, Davis, Davis, CA 5616-8669, USA.

Background: Quantitation of human vitamin E metabolism is incomplete, so we quantified RRR- and all-rac-alpha-tocopherol metabolism in an adult.

Objective: The objective of the study was to quantify and interpret in vivo human vitamin E metabolism.

Design: A man was given an oral dose of 0.001821 micromol [5-14CH3]RRR-alpha-tocopheryl acetate (with 101.5 nCi 14C), and its fate in plasma, plasma lipoproteins, urine, and feces was measured over time. Data were analyzed and interpreted by using kinetic modeling. The protocol was repeated later with 0.001667 micromol [5-14CH3]all-rac-alpha-tocopheryl acetate (with 99.98 nCi 14C).

Results: RRR-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate were absorbed equally well (fractional absorption: approximately 0.775). The main route of elimination was urine, and approximately 90% of the absorbed dose was alpha-2(2'-carboxyethyl)-6-hydroxychroman. Whereas 93.8% of RRR-alpha-tocopherol flow to liver kinetic pool B from plasma was returned to plasma, only 80% of the flow of all-rac-alpha-tocopherol returned to plasma; the difference (14%) was degraded and eliminated. Thus, for newly digested alpha-tocopherol, the all-rac form is preferentially degraded and eliminated over the RRR form. Respective residence times in liver kinetic pool A and plasma for RRR-alpha-tocopherol were 1.16 and 2.19 times as long as those for all-rac-alpha-tocopherol. Model-estimated distributions of plasma alpha-tocopherol, extrahepatic tissue alpha-tocopherol, and liver kinetic pool B for RRR-alpha-tocopherol were, respectively, 6.77, 2.71, and 3.91 times as great as those for all-rac-alpha-tocopherol. Of the lipoproteins, HDL had the lowest 14C enrichment. Liver had 2 kinetically distinct alpha-tocopherol pools.

Conclusions: Both isomers were well absorbed; all-rac-alpha-tocopherol was preferentially degraded and eliminated in urine, the major route. RRR-alpha-tocopherol had a longer residence time and larger distribution than did all-rac-alpha-tocopherol. Liver had 2 distinct alpha-tocopherol pools. The model is a hypothesis, its estimates are model-dependent, and it encourages further testing.
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http://dx.doi.org/10.1093/ajcn/84.6.1430DOI Listing
December 2006

Quantitation of in vivo human folate metabolism.

Am J Clin Nutr 2004 Sep;80(3):680-91

Departments of Nutrition and Pathology Department, University of California-Davis, One Shields Avenue,. Davis. CA 95616-8669, USA.

Background: A quantitative understanding of human folate metabolism is needed.

Objective: The objective was to quantify and interpret human folate metabolism as it might occur in vivo.

Design: Adults (n = 13) received 0.5 nmol [(14)C]pteroylmonoglutamate (100 nCi radioactivity) plus 79.5 nmol pteroylmonoglutamate in water orally. (14)C was measured in plasma, erythrocytes, urine, and feces for >/=40 d. Kinetic modeling was used to analyze and interpret the data.

Results: According to the data, the population was healthy and had a mean dietary folate intake of 1046 nmol/d, and the apparent dose absorption of (14)C was 79%. The model predictions showed that only 0.25% of plasma folate was destined for marrow, mean bile folate flux was 5351 nmol/d, and the digestibility of the mix (1046 + 5351 nmol/d) was 92%. About 33% of visceral pteroylmonoglutamate was converted to the polyglutamate form, most of the body folate was visceral (>99%), most of the visceral folate was pteroylpolyglutamate (>98%), total body folate was 225 micromol, and pteroylpolyglutamate synthesis, recycling, and catabolism were 1985, 1429, and 556 nmol/d, respectively. Mean residence times were 0.525 d as visceral pteroylmonoglutamate, 119 d as visceral pteroylpolyglutamate, 0.0086 d as plasma folate, and 0.1 d as gastrointestinal folate.

Conclusions: Across subjects, folate absorption, bile folate flux, and body folate stores were larger than prior estimates. Marrow folate uptake and pteroylpolyglutamate synthesis, recycling, and catabolism are saturable processes. Visceral pteroylpolyglutamate was an immediate precursor of plasma p-aminobenzoylglutamate. The model is a working hypothesis with derived features that are explicitly model-dependent. It successfully quantitated folate metabolism, encouraging further rigorous testing.
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http://dx.doi.org/10.1093/ajcn/80.3.680DOI Listing
September 2004
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