Detecting interaction(s) and assessing the impact of component subsets in a chemical mixture using fixed-ratio mixture ray designs

An important environmental and regulatory issue is the protection of human health from potential adverse effects of cumulative exposure to multiple chemicals. Earlier literature suggested restricting inference to specific fixed-ratio rays of interest. Based on appropriate definitions of additivity, single chemical data are used to predict the relationship among the chemicals under the zero-interaction case. Parametric comparisons between the additivity model and the model fit along the fixed-ratio ray(s) are used to detect departure from additivity. Collection of data along reduced fixed-ratio rays, where subsets of chemicals of interest are removed from the mixture and the remaining compounds are at the same relative ratios as considered in the full ray, allow researchers to make inference about the effect of the removed chemicals. Methods for fitting simultaneous confidence bands about the difference between the best fitting model and the model predicted under additivity are developed to identify regions along the rays where significant interactions occur. This general approach is termed the “single chemicals required” (SCR) method of analysis. A second approach, termed “single chemicals not required” (SCNR) method of analysis, is based on underlying assumptions about the parameterization of the response surface. Under general assumptions, polynomial terms for models fit along fixed-ratio rays are associated with interaction terms. Consideration is given to the case where only data along the mixture rays are available. Tests of hypotheses, which consider interactions due to subsets of chemicals, are also developed.     

Nutritional value of a highly digestible sorghum cultivar for meat-type chickens

The nutritional value of a newly discovered sorghum mutant cultivar (P851171), with high in vitro protein digestibility, was compared to those of corn and two normal sorghums (P721N and 611Y) in two chick feeding trials. Although 8-20 day protein efficiency ratios and net protein ratios of all three sorghums were inferior to those of corn, P851171 and 611Y had markedly greater mean true amino acid digestibilities (TAAD) than either corn or P721N. In a subsequent 42-day experiment, all three sorghums supported weight gains equal to those of the corn-fed chicks. Feeding suboptimal levels of dietary protein resulted in reduced weight gains and no observed benefits of P851171 or 611Y. Furthermore, chicks fed P851171 exhibited poorer feed/gain values as compared to those fed the other cereals. It is possible that the starch content/carbohydrate profile of P851171 was inferior to that of the other sorghums, which offset its superior TAAD and resulted in poorer broiler performance.     

A Bayesian hierarchical model for risk assessment of methylmercury

This article uses a Bayesian hierarchical model to quantify the adverse health effects associated with in-utero exposure to methylmercury. By allowing for study-to-studyas well as outcome-to-outcome variability, the approach provides a useful meta-analytic tool for multi-outcome, multi-study environmental risk assessments. The analysis presented here expands on the findings of a National Academy of Sciences (NAS) committee, charged with advising the United States Environmental Protection Agency (EPA) on an appropriate approach to conducting a risk assessment for methylmercury. The NAS committee, for which the senior author (Ryan) was a committee member, reviewed the findings from several conflicting studies and reported the results from a Bayesian hierarchical model that synthesized information across several studies and for several outcomes. Although the NAS committee did not suggest that the hierarchical model be used as the actual basis for a methylmercury risk assessment, the results from the model were used to justify and support the final recommendation that the risk analysis be based on data from a study conducted in the Faroe Islands, which had found a positive association between in-utero exposure to methylmercury and impaired neurological development. We considera variety of statistical issues, but particularly sensitivity to model specification.     

Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state

Tolerant self-antigen-specific CD8 T cells fail to proliferate in response to antigen, thereby preventing autoimmune disease. By using an in vivo mouse model, we show that tolerant T cells proliferate and become functional under lymphopenic conditions, even in a tolerogenic environment. However, T cell rescue is only transient, with tolerance reimposed upon lymphorepletion even in the absence of tolerogen (self-antigen), challenging the prevailing paradigm that continuous antigen exposure is critical to maintain tolerance. Genome-wide messenger RNA and microRNA profiling revealed that tolerant T cells have a tolerance-specific gene profile that can be temporarily overridden under lymphopenic conditions but is inevitably reimposed, which suggests epigenetic regulation. These insights into the regulatory mechanisms that maintain or break self-tolerance may lead to new strategies for the treatment of cancer and autoimmunity.     

Soil carbon distribution and quality in a montane rangeland-forest mosaic in northern Utah

Relatively little is known about soil organic carbon (SOC) dynamics in montane ecosystems of the semi-arid western U.S. or the stability of current SOC pools under future climate change scenarios. We measured the distribution and quality of SOC in a mosaic of rangeland-forest vegetation types that occurs under similar climatic conditions on non-calcareous soils at Utah State University's T.W. Daniel Experimental Forest in northern Utah: the forest types were aspen [Populus tremuloides] and conifer (mixture of fir [Abies lasiocarpa] and spruce [Picea engelmannii]); the rangeland types were sagebrush steppe [Artemisia tridentata], grass-forb meadow, and a meadow-conifer ecotone. Total SOC was calculated from OC concentrations, estimates of bulk density by texture and rock-free soil volume in five pedons. The SOC quality was expressed in terms of leaching potential and decomposability. Amount and aromaticity of water-soluble organic carbon (DOC) was determined by water extraction and specific ultra violet absorbance at 254 nm (SUVA) of leached DOC. Decomposability of SOC and DOC was derived from laboratory incubation of soil samples and water extracts, respectively.

Although there was little difference in total SOC between soils sampled under different vegetation types, vertical distribution, and quality of SOC appeared to be influenced by vegetation. Forest soils had a distinct O horizon and higher SOC concentration in near-surface mineral horizons that declined sharply with depth. Rangeland soils lacked O horizons and SOC concentration declined more gradually. Quality of SOC under rangelands was more uniform with depth and SOC was less soluble and less decomposable (i.e., more stable) than under forests. However, DOC in grass-forb meadow soils was less aromatic and more bioavailable, likely promoting C retention through cycling. The SOC in forest soils was notably more leachable and decomposable, especially near the soil surface, with stability increasing with soil depth. Across the entire dataset, there was a weak inverse relationship between the decomposability and the aromaticity of DOC. Our data indicate that despite similar SOC pools, vegetation type may affect SOC retention capacity under future climate projections by influencing potential SOC losses via leaching and decomposition.     

Effect of dextransucrase cellobiose acceptor products on the growth of human gut bacteria

The selective fermentation by human gut bacteria of gluco-oligosaccharides obtained from the reaction between the glucosyl group of sucrose and cellobiose, catalyzed by dextransucrases (DSR) from Leuconostoc mesenteroides , has been evaluated. Oligosaccharides were fractionated according to their molecular weight, and their effect on the growth of different bacterial groups was studied. To determine the structure (position and configuration of glycosidic linkages)-function relationship, their properties were compared to those of DSR maltose acceptor products (DSRMal) and of recognized prebiotic carbohydrates (fructo-oligosaccharides, FOS). Cellobiose acceptor products (DSRCel) showed bifidogenic properties similar to those of FOS. However, no significant differences related to molecular weight or isomeric configurations were found for DSRCel and DSRMal products.     

Textural Comparisons of Gluten‐Free and Wheat‐Based Doughs,Batters, and Breads

Studies were conducted with two newly developed gluten‐free bread recipes. One was based on corn starch (relative amount 54), brown rice (25), soya (12.5), and buckwheat flour (8.5), while the other contained brown rice flour (50), skim milk powder (37.5), whole egg (30), potato (25), and corn starch (12.5), and soya flour (12.5). The hydrocolloids used were xanthan gum (1.25) and xanthan (0.9) plus konjac gum (1.5), respectively. Wheat bread and gluten‐free bread made from commercial flour mix were included for comparison. Baking tests showed that wheat and the bread made from the commercial flour mix yielded significantly higher loaf volumes (P < 0.01). All the gluten‐free breads were brittle after two days of storage, detectable by the occurrence of fracture, and the decrease in springiness (P < 0.01), cohesiveness (P < 0.01), and resilience (P < 0.01) derived from texture profile analysis. However, these changes were generally less pronounced for the dairy‐based gluten‐free bread, indicating a better keeping quality. Confocal laser‐scanning microscopy showed that the dairy‐based gluten‐free bread crumb contained network‐like structures resembling the gluten network in wheat bread crumb. It was concluded that the formation of a continuous protein phase is critical for an improved keeping quality of gluten‐free bread.