Environmental fate of the chemical mixtures: Crude oil,JP‐5, mineral spirits,and diesel fuel

Petroleum hydrocarbon mixtures in soils and groundwater present unique challenges in the estimation of potential human exposures and subsequent health risks. A major component of risk assessment affected by mixtures is the evaluation of environmental fate. The fate of petroleum mixtures may be evaluated by using either of three approaches: (1) the evaluation of the fate of indicator chemical(s), (2) the evaluation of the fate of the mixture as a whole with a surrogate, and (3) the evaluation of the fate of the hydrocarbon mixture as a whole. The limiting factor in the selection of an approach is the availability of information on specific chemical constituents in the mixture. The evaluation of environmental fate requires quantitative information regarding the distribution, mobility, and degradation/transformation as represented by various physicochemical properties. In addition to the availability of this information, the selection of the evaluation method should be consistent with the goals of the project, as each approach will produce different results. This presentation discusses the issues related to the identification and implementation of each of the approaches to the evaluation of the environmental fate of four petroleum mixtures (crude oil, JP‐5, mineral spirits, and diesel) for risk assessment purposes.     

Selection of suitable housekeeping genes for expression analysis in glioblastoma using quantitative RT-PCR

Background  

Considering the broad variation in the expression of housekeeping genes among tissues and experimental situations, studies using quantitative RT-PCR require strict definition of adequate endogenous controls. For glioblastoma, the most common type of tumor in the central nervous system, there was no previous report regarding this issue.     

Understorey thinning and burning trials are needed in conservation reserves: The case of Tuart (Eucalyptus gomphocephala D.C.)

Summary Management interventions are needed to reverse the decline of Tuart (Eucalyptus gomphocephala) woodland in the Yalgorup area of south‐west Western Australia where the largest intact remaining example of this ecosystem is located. Although the cause of the decline is uncertain and several factors may be involved, management action should not be withheld because the decline process is not fully understood. We contend that the reduction in fire frequency over the last 50 years has led to an increase in understorey density, particularly of Western Australian Peppermint (Agonis flexuosa), resulting in greater competition for resources, which may in turn have increased the susceptibility of healthy woodland to decline. In contrast to Tuart regeneration, which is usually tied to fire, Western Australian Peppermint can establish readily in unburnt woodland. Further, once Western Australian Peppermint seedlings develop to the lignotuberous stage, they can resprout vigorously after fire. Therefore, a combination of fire and the physical removal of understorey in sites where this species has formed extensive thickets is required to: (i) provide an opportunity for regeneration of Tuart in both healthy and declining stands; (ii) improve the chances of sustained recovery of Tuart trees in declining stands; and (iii) ensure heterogeneity in the vegetation at multiple scales, a recognized strategy for conserving biodiversity and increasing ecosystem resilience. We propose that this approach may also be relevant to other tree decline syndromes in southern Australia. However, fostering community support for active intervention using thinning and fire in conservation reserves and staging the operations within an experimental framework will be important for such action to gain both the social and scientific acceptance necessary for it to be applied widely.     

Leveraging a surrogate outcome to improve inference on a partially missing target outcome

Sample sizes vary substantially across tissues in the Genotype-Tissue Expression (GTEx) project, where considerably fewer samples are available from certain inaccessible tissues, such as the substantia nigra (SSN), than from accessible tissues, such as blood. This severely limits power for identifying tissue-specific expression quantitative trait loci (eQTL) in undersampled tissues. Here we propose Surrogate Phenotype Regression Analysis (Spray ) for leveraging information from a correlated surrogate outcome (eg, expression in blood) to improve inference on a partially missing target outcome (eg, expression in SSN). Rather than regarding the surrogate outcome as a proxy for the target outcome, Spray jointly models the target and surrogate outcomes within a bivariate regression framework. Unobserved values of either outcome are treated as missing data. We describe and implement an expectation conditional maximization algorithm for performing estimation in the presence of bilateral outcome missingness. Spray estimates the same association parameter estimated by standard eQTL mapping and controls the type I error even when the target and surrogate outcomes are truly uncorrelated. We demonstrate analytically and empirically, using simulations and GTEx data, that in comparison with marginally modeling the target outcome, jointly modeling the target and surrogate outcomes increases estimation precision and improves power.     

Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes

Isoforms in the PDE1 family of cyclic nucleotide phosphodiesterases were recently found to comprise a significant portion of the cGMP-inhibited cAMP hydrolytic activity in human hearts. We examined the expression of PDE1 isoforms in human myocardium, characterized their catalytic activity, and quantified their contribution to cAMP hydrolytic and cGMP hydrolytic activity in subcellular fractions of this tissue. Western blotting with isoform-selective anti-PDE1 monoclonal antibodies showed PDE1C1 to be the principal isoform expressed in human myocardium. Immunohistochemical analysis showed that PDE1C1 is distributed along the Z-lines and M-lines of cardiac myocytes in a striated pattern that differs from that of the other major dual-specificity cyclic nucleotide phosphodiesterase in human myocardium, PDE3A. Most of the PDE1C1 activity was recovered in soluble fractions of human myocardium. It binds both cAMP and cGMP with K(m) values of approximately 1 microm and hydrolyzes both substrates with similar catalytic rates. PDE1C1 activity in subcellular fractions was quantified using a new PDE1-selective inhibitor, IC295. At substrate concentrations of 0.1 microm, PDE1C1 constitutes the great majority of cAMP hydrolytic and cGMP hydrolytic activity in soluble fractions and the majority of cGMP hydrolytic activity in microsomal fractions, whereas PDE3 constitutes the majority of cAMP hydrolytic activity in microsomal fractions. These results indicate that PDE1C1 is expressed at high levels in human cardiac myocytes with an intracellular distribution distinct from that of PDE3A and that it may have a role in the integration of cGMP-, cAMP- and Ca(2+)-mediated signaling in these cells.     

Effects of 8-week strength training with two models of chest press machines on muscular activity pattern and strength.

The purposes of this study were to assess: (i) the effects of 8-week training programs with constrained-path and unconstrained-path chest press machines on 1-RM; (ii) the different activity patterns of selected arm and shoulder girdle muscles during push movement performed on the different machines; (iii) the transfer of the training effects from one machine to the other. Twenty healthy, sedentary women (mean+/-SD age, 24.8+/-1.0yrs), randomized to either the FM or CM strength training protocols were evaluated before and after the strength training program. Muscular activity signals were recorded by surface electromyography (sEMG) from eight muscles while each subject performed the exercise on each machine. Muscle strength was defined by a 1 repetition maximum (1-RM) test for each subject on each machine. Both machines were effective in improving 1-RM, but the 1-RM increased more in the FM than the CM. Adaptive change in the sEMG was observed in all muscles after training on the FM machine, but not within the stabilizers when training on the CM machine. The results suggest that training in an unconstrained condition provides a more effective method for improving inter-muscular coordination via adaptation of the motor strategy aimed at optimising muscular efforts.     

Genomic analysis of the relationship between gene expression variation and DNA polymorphism in Drosophila simulans

Background

Understanding how DNA sequence polymorphism relates to variation in gene expression is essential to connecting genotypic differences with phenotypic differences among individuals. Addressing this question requires linking population genomic data with gene expression variation.

Results

Using whole genome expression data and recent light shotgun genome sequencing of six Drosophila simulans genotypes, we assessed the relationship between expression variation in males and females and nucleotide polymorphism across thousands of loci. By examining sequence polymorphism in gene features, such as untranslated regions and introns, we find that genes showing greater variation in gene expression between genotypes also have higher levels of sequence polymorphism in many gene features. Accordingly, X-linked genes, which have lower sequence polymorphism levels than autosomal genes, also show less expression variation than autosomal genes. We also find that sex-specifically expressed genes show higher local levels of polymorphism and divergence than both sex-biased and unbiased genes, and that they appear to have simpler regulatory regions.

Conclusion

The gene-feature-based analyses and the X-to-autosome comparisons suggest that sequence polymorphism in cis-acting elements is an important determinant of expression variation. However, this relationship varies among the different categories of sex-biased expression, and trans factors might contribute more to male-specific gene expression than cis effects. Our analysis of sex-specific gene expression also shows that female-specific genes have been overlooked in analyses that only point to male-biased genes as having unusual patterns of evolution and that studies of sexually dimorphic traits need to recognize that the relationship between genetic and expression variation at these traits is different from the genome as a whole.     

In utero infection by porcine reproductive and respiratory syndrome virus is sufficient to increase susceptibility of piglets to challenge by Streptococcus suis type II

Porcine reproductive and respiratory syndrome (PRRS) consistently elevates the frequency of disease and mortality in young pigs. Many different secondary bacterial diseases occur in PRRS virus (PRRSV)-infected pigs. However, to date, establishing a reproducible experimental model of PRRSV infection in weaned pigs, with subsequent clinical disease following secondary bacterial challenge, has been difficult. PRRSV is frequently isolated during outbreaks from weak-born piglets affected by secondary bacterial diseases. This study was performed to investigate the potential role of intrauterine PRRSV infection on piglet susceptibility to secondary bacterial infection. PRRSV-free pregnant sows were intranasally infected at 98 days of gestation with PRRSV strain SD 23983. All piglets born to the PRRSV-infected sows were viremic. Piglets were removed from the sows at birth and deprived of colostrum. Piglets from PRRSV-infected and noninfected sows were randomly assigned to Streptococcus suis challenge or control subgroups. At 5 days of age, piglets were challenged intranasally with strain MN 87555 of S. suis type II. Total and differential leukocyte counts were performed on blood samples collected at 3 days of age. The numbers of leukocytes, lymphocytes, and monocytes were significantly reduced in the PRRSV-infected piglets. Lesions were observed in bone marrow, brain, lung, heart, spleen, lymph node, tonsil, and thymus of PRRSV-infected piglets. Thymus/body weight ratios of in utero PRRSV-infected piglets were significantly reduced compared to those of non-PRRSV-infected piglets, and thymic lesions were characterized by severe cortical depletion of thymocytes. Lesions were not observed in piglets born to PRRSV-free sows. Overall, 20 out of 22 piglets in the PRRSV-S. suis dual-infection group died within 1 week after challenge with S. suis (10 of 11 in each of two trials). This contrasts with 1 of 18 piglets in the PRRSV-infection-only group and 5 of 23 piglets in the S. suis-challenge-only group (1 of 12 in trial 1 and 4 of 11 in trial 2). No piglets died in the uninfected control groups. Most of the piglets in the PRRSV-S. suis dual-infection group developed suppurative meningitis. S. suis type II was recovered from their brains and joints. These results indicate that in utero infection by PRRSV makes piglets more susceptible to infection and disease following challenge by S. suis type II. In utero infection by PRRSV may provide a useful model to study the interaction between PRRSV and bacterial coinfections in piglets.