Effect of Maternal Ethanol Consumption during Pregnancy and Lactation on Kinetic Parameters of Folic Acid Intestinal Transport in Suckling Rats

Ethanol ingestion is known to interfere with folate absorption and metabolism. A fostering/crossfostering analysis of maternal ethanol exposure effects on jejunum and ileum kinetic parameters in vivo of offspring rat folic acid absorption at 21 days postpartum was carried out. The rats were divided into four groups: CP, control pups; GP, pups exposed to ethanol only during gestation; LP, pups exposed to ethanol only during lactation; GLP, pups exposed to ethanol during gestation and lactation. Jejunal and ileal loop transport studies were performed using in vivo perfusion at a flow rate of 3 ml/min for 5 min. Folic acid concentrations of 0.25, 0.5, 1, 1.5 and 2.5 μm were used. Jejunal and ileal absorption values were determined by the difference between the initial and the final amounts of substrate in the perfusate and expressed as picomoles per square centimeter of intestinal surface every 5 min. The results indicated that ethanol consumption by the dams during gestation and/or lactation led to significant changes in V _max, with no significant changes in apparent K _m. These findings suggest that exposure to ethanol during gestational and suckling periods leads to a general delay in postnatal body weight and that intestinal folate absorption appears to be upregulated in suckling rats, this effect being higher in the LP group.     

Rapid measurement of deuterium-labeled long-chain fatty acids in plasma by HPLC-ESI-MS

Imbalanced fatty acid metabolism contributes significantly to the increased incidence of metabolic disorders. Isotope-labeled fatty acids (2H, 13C) provide efficient means to trace fatty acid metabolism in vivo. This study reports a new and rapid method for the quantification of deuterium-labeled fatty acids in plasma by HPLC-MS. The sample preparation protocol developed required only hydrolysis, neutralization, and quenching steps followed by high-performance liquid chromatography-electrospray ionization-mass spectrometry analysis in negative ion mode using single ion monitoring. Deuterium-labeled stearic acid (d7-C18:0) was synthesized to reduce matrix interference observed with d5 analog, which improved the limit of detection (LOD) significantly, depending on the products analyzed. Linearity > 0.999 between the LOD (100 nM) and 30 microM, accuracy > 90%, precision > 88%, and adequate recovery in the dynamic range were obtained for d7-C18:0 and d7-oleic acid (C18:1). Upon oral dosing of d7-C18:0 in rats, the parent compound and its desaturation and beta-oxidation products, d7-C18:1 and d7-C16:0, were circulating with a maximal concentration ranging from 0.6 to 2.2 microM, with significant levels of d7-fatty acids detected for up to 72 h.     

The log multinomial regression model for nominal outcomes with more than two attributes

An estimate of the risk or prevalence ratio, adjusted for confounders, can be obtained from a log binomial model (binomial errors, log link) fitted to binary outcome data. We propose a modification of the log binomial model to obtain relative risk estimates for nominal outcomes with more than two attributes (the "log multinomial model"). Extensive data simulations were undertaken to compare the performance of the log multinomial model with that of an expanded data multinomial logistic regression method based on the approach proposed by Schouten et al. (1993) for binary data, and with that of separate fits of a Poisson regression model based on the approach proposed by Zou (2004) and Carter, Lipsitz and Tilley (2005) for binary data. Log multinomial regression resulted in "inadmissable" solutions (out-of-bounds probabilities) exceeding 50% in some data settings. Coefficient estimates by the alternative methods produced out-of-bounds probabilities for the log multinomial model in up to 27% of samples to which a log multinomial model had been successfully fitted. The log multinomial coefficient estimates generally had lesser relative bias and mean squared error than the alternative methods. The practical utility of the log multinomial regression model was demonstrated with a real data example. The log multinomial model offers a practical solution to the problem of obtaining adjusted estimates of the risk ratio in the multinomial setting, but must be used with some care and attention to detail.     

Exact one-sided confidence bounds for the risk ratio in 2 x 2 tables with structural zero

This paper examines exact one-sided confidence limits for the risk ratio in a 2 x 2 table with structural zero. Starting with four approximate lower and upper limits, we adjust each using the algorithm of Buehler (1957) to arrive at lower (upper) limits that have exact coverage properties and are as large (small) as possible subject to coverage, as well as an ordering, constraint. Different Buehler limits are compared by their mean size, since all are exact in their coverage. Buehler limits based on the signed root likelihood ratio statistic are found to have the best performance and recommended for practical use.     

Probing the dynamics of intact cells and nuclear envelope precursor membrane vesicles by deuterium solid state NMR spectroscopy

Membrane dynamics is an essential part of many cellular mechanisms such as intracellular trafficking, membrane fusion/fission and mitotic organelle reconstitution. The dynamics of membranes is dependent primarily on their phospholipid and cholesterol composition and how these molecules are ordered in relation to one another. To determine the physical status of membranes in whole cells or purified membranes of subcellular compartments we have developed a novel application exploiting solid-state ²H-NMR spectroscopy. We utilise this method to probe the dynamics of intact sperm and nuclear envelope precursor membranes. We show, using mass spectrometry, that either multilamellar or small unilamellar vesicles of deuterium-labelled palmitoyl-oleoylphosphatidylcholine can be used to probe the dynamics of sperm cells or nuclear envelope precursor membrane vesicles, respectively. Using ²H-NMR we determine the order parameters of sperm cells and nuclear envelope precursor membrane vesicles. We demonstrate that whole sperm membranes are more dynamic than nuclear envelope precursor membranes due to the higher cholesterol levels of the latter. Our new application can be exploited as a generic method for monitoring membrane dynamics in whole cells, various subcellular membrane compartments and membrane domains in subcellular compartments.     

Using sparse survey data to investigate the declining abundance of British harbour seals

This study presents an analysis of changes in the regional abundance of harbour seals Phoca vitulina based on repeated aerial surveys of haulouts, and demonstrates the use of sparse data to deliver advice about population status and management. Generalized linear models with negative binomial errors were used to represent these overdispersed data. The shape parameter of the negative binomial distribution was directly estimated from the data where this was possible. Information from time-series of counts where there were few gaps in the data was used to improve the estimation of this parameter in areas where fewer surveys had been carried out. The results show that the number of harbour seals in eastern England has not increased since the end of the 2002 phocine distemper epidemic. There is also evidence of a general decline in most of the large harbour seal colonies around Britain. The populations in the Inner Hebrides were an exception, with numbers appearing to be stable or increasing. Between 2001 and 2006, the population in Orkney and Shetland declined by 40% (95% confidence interval: 30–50%), indicating harbour seals in these areas experienced substantially increased mortality or very low recruitment over this period. The widespread declines, ranging from Shetland to The Wash, suggest that the causes may have been present over a large part of the North Sea.     

Assessing plant-nutrient relationships in highly invaded Californian grasslands using non-normal probability distributions

Question: Is native species occurrence related to soil nutrients in highly invaded Californian annual grasslands? What is the best method to analyze this relationship, given that native species occur in very low numbers and are absent from many locations? Location: California, USA. Methods: We investigated the effects of soil characteristics and livestock grazing on native plant occurrence at 40 plots from six sites during the period 2003–2005. Low absolute cover (< 5.8%) of native species resulted in strongly skewed, zero-inflated data sets. To overcome problems in the analysis created by non-normality and correlations within plots, we used GLMs and GLMMs, either with a Poisson or a negative binomial distribution, to analyse native species richness and Nassella pulchra cover. Results: N. pulchra cover was strongly associated with low phosphorus in sandy soils, whereas native species richness was highest in soils with low available nitrogen (high C:N). Conclusion: Under current conditions, phosphorus seems to be a critical factor influencing abundance of N. pulchra. Low fertility soils may provide refugia for native species in highly invaded California grasslands as they may be below a threshold required for non-native annuals to completely dominate. By using non-normal distributions in linear models with random components, we report well fitted models with more accurately tested significant covariates.     

气候和流域特征变化对淮河流域地表水文过程的影响

定量认识和理解气候与流域特征变化对淮河流域地表水文过程的影响,可以为科学管理淮河流域水资源提供重要的理论参考和技术支撑。评估了多控制因子联立求解归因方法的适用性,以此量化了淮河流域气候和Budyko参数n对不同年代蒸散发(ET)、径流变化(较基准期1961—1980年)的贡献,并且进行了归因分析,结果表明：1)多控制因子联立求解法可以准确有效地分离气候和参数n对ET和径流变化的贡献。2)在气候和参数n变化的共同影响下,20世纪80年代、90年代的ET和径流在沂沭泗河各水文分区均呈减小趋势,而在上游和中游各水文分区的变化则表现出明显的时空差异性。3)就各年代控制ET变化的主要因子,多数水文分区为参数n,其次为降水和潜在蒸散发(PET),分别集中在沂沭泗河地区和淮河上游。20世纪80年代,中游水文分区径流变化的主控因子为PET,其他水文分区则多为降水;而20世纪90年代和21世纪初多数水文分区的主控因子为参数n,其次为降水。总之,控制淮河流域ET和径流变化的物理机制具有明显的空间差异和年代际变化特征。