A mathematical model of the in vitro keratinocyte response to chromium and nickel exposure

A mathematical model describing the main mechanistic processes involved in keratinocyte response to chromium and nickel has been developed and compared to experimental in vitro data. Accounting for the interactions between the metal ions and the keratinocytes, the law of mass action was used to generate ordinary differential equations which predict the time evolution and ion concentration dependency of keratinocyte viability, the amount of metal associated with the keratinocytes and the release of cytokines by the keratinocytes. Good agreement between model predictions and existing experimental data of these endpoints was observed, supporting the use of this model to explore physiochemical parameters that influence the toxicological response of keratinocytes to these two metals.

Clonal variation in acetylcholinesterase biomarkers and life history traits following OP exposure in Daphnia magna

Two clones of Daphnia magna (Standard and Ruth) were exposed for 7 days to sub-lethal concentrations of acephate (5.0 and 10.0 mg/L). Survivorship, individual growth, reproduction and the population growth rate (lambda) were evaluated over three weeks. Acetylcholinesterase (AChE) activity was measured on days 2, 7 and 21. Acephate exposure inhibited AChE activity but had no direct effect on life history (LH) traits. There was also no effect of clone on AChE activity, LH and lambda. However, a significant interaction between clone and acephate concentration was found on both fecundity and AChE inhibition at 48 h was associated with a decrease in lambda the Standard clone and an increase in lambda in clone Ruth. Therefore, our findings show that genotypic variation will influence the link between AChE activity and toxic effects at higher levels of biological organisation in D. magna. (c) 2007 Elsevier Inc. All rights reserved.

Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder

Objective: To evaluate cortisol suppression following 0.5 mg of dexamethasone (DEX) in trauma survivors (N = 52),with posttraumatic stress disorder (PTSD), major depressive disorder (MDD), both, or neither disorder, and in subjects never exposed to trauma (N = 10), in order to examine interactions between diagnosis and trauma history on cortisol negative feedback inhibition. Method: Lifetime trauma exposure and psychiatric diagnoses were assessed and blood samples were obtained at 8:00 a.m. for the determination of baseline cortisol. Participants ingested 0.5 mg of DEX at 11:00 p.m. and blood samples for determination of cortisol and DEX were obtained at 8:00 a.m. the following day. Results: PTSD was associated with enhanced cortisol suppression in response to DEX Among trauma survivors, the presence of a traumatic event prior to the "focal" trauma had a substantial impact on cortisol suppression in subjects with MDD. Such subjects were more likely to show cortisol alterations similar to those associated with PTSD, whereas subjects with MDD with no prior trauma were more likely to show alterations in the opposite direction, i.e. relative non-suppression. Conclusions: Cortisol hypersuppression in PTSD appears not to be dependent on the presence of traumatic events prior to the focal trauma. However, prior trauma exposure may affect cortisol suppression in MDD. This finding may have implications for understanding why only some depressed patients show non-suppression on the DST. Published by Elsevier Ltd.

The effects of pre- and postnatal depression in fathers: a natural experiment comparing the effects of exposure to depression on offspring

Background: Depression in fathers in the postnatal period is associated with an increased risk of behavioural problems in their offspring, particularly for boys. The aim of this study was to examine for differential effects of depression in fathers on children's subsequent psychological functioning via a natural experiment comparing prenatal and postnatal exposure. Methods:In a longitudinal population cohort study (the Avon Longitudinal Study of Parents and Children (ALSPAC)) we examined the associations between depression in fathers measured in the prenatal and postnatal period (measured using the Edinburgh Postnatal Depression Scale), and later behavioural/emotional and psychiatric problems in their children, assessed at ages 31/2 and 7 years. Results: Children whose fathers were depressed in both the prenatal and postnatal periods had the highest risks of subsequent psychopathology, measured by total problems at age 31/2 years (Odds Ratio 3.55; 95% confidence interval 2.07, 6.08) and psychiatric diagnosis at age 7 years (OR 2.54; 1.19, 5.41). Few differences emerged when prenatal and postnatal depression exposure were directly compared, but when compared to fathers who were not depressed, boys whose fathers had postnatal depression only had higher rates of conduct problems aged 31/2 years (OR 2.14; 1.22, 3.72) whereas sons of the prenatal group did not (OR 1.41; .75, 2.65). These associations changed little when controlling for maternal depression and other potential confounding factors. Conclusions: The findings of this study suggest that the increased risk of later conduct problems, seen particularly in the sons of depressed fathers, maybe partly mediated through environmental means. In addition, children whose fathers are more chronically depressed appear to be at a higher risk of emotional and behavioural problems. Efforts to identify the precise mechanisms by which transmission of risk may occur should be encouraged to enable the development of focused interventions to mitigate risks for young children.

Picture book exposure elicits positive visual preferences in toddlers

Although the relationship between "mere exposure" and attitude enhancement is well established in the adult domain, there has been little similar work with children. This article examines whether toddlers' visual attention toward pictures of foods can be enhanced by repeated visual exposure to pictures of foods in a parent-administered picture book. We describe three studies that explored the number and nature of exposures required to elicit positive visual preferences for stimuli and the extent to which induced preferences generalize to other similar items. Results show that positive preferences for stimuli are easily and reliably induced in children and, importantly, that this effect of exposure is not restricted to the exposed stimulus per se but also applies to new representations of the exposed item. (C) 2009 Elsevier Inc. All rights reserved.

Exposure to postnatal depression predicts elevated cortisol in adolescent offspring

Background. Animal research shows that early adverse experience results in altered glucocorticoid levels in adulthood, either raised basal levels or accentuated responses to stress. If a similar phenomenon operates in humans, this suggests a biological mechanism whereby early adversity might transmit risk for major depression, glucocorticoid elevations being associated with the development of this disorder. Methods. We measured salivary cortisol at 8:00 Am and 8:00 Pm over 10 days in 13-year-old adolescents who had (n = 48) or bad not (n = 39) been exposed to postnatal maternal depression. Results: Maternal postnatal depression was associated with higher, more variable morning cortisol in offspring, a pattern previously found to predict major depression. Conclusions. Early adverse experiences might alter later steroid levels in humans. Because maternal depression confers added risk for depression to children, these alterations might provide a link between early events and later psychopathology.

Gene transcription in Daphnia magna: effects of acute exposure to a carbamate insecticide and an acetanilide herbicide.

Daphnia magna is a key invertebrate in the freshwater environment and is used widely as a model in ecotoxicological measurements and risk assessment. Understanding the genomic responses of D. magna to chemical challenges will be of value to regulatory authorities worldwide. Here we exposed D. magna to the insecticide methomyl and the herbicide propanil to compare phenotypic effects with changes in mRNA expression levels. Both pesticides are found in drainage ditches and surface water bodies standing adjacent to crops. Methomyl, a carbamate insecticide widely used in agriculture, inhibits acetylcholinesterase, a key enzyme in nerve transmission. Propanil, an acetanilide herbicide, is used to control grass and broad-leaf weeds. The phenotypic effects of single doses of each chemical were evaluated using a standard immobilisation assay. Immobilisation was linked to global mRNA expression levels using the previously estimated 48h-EC(1)s, followed by hybridization to a cDNA microarray with more than 13,000 redundant cDNA clones representing >5000 unique genes. Following exposure to methomyl and propanil, differential expression was found for 624 and 551 cDNAs, respectively (one-way ANOVA with Bonferroni correction, P

Response of porcine intestinal in vitro organ culture tissues following exposure to Lactobacillus plantarum JC1 and Salmonella Typhimurium SL1344.

The development of novel intervention strategies for the control of zoonoses caused by bacteria such as Salmonella spp. in livestock requires appropriate experimental models to assess their suitability. Here, a novel porcine intestinal in vitro organ culture (IVOC) model utilizing cell crown (CC) technology (CCIVOC) (Scaffdex) was developed. The CCIVOC model was employed to investigate the characteristics of association of S. enterica serovar Typhimurium strain SL1344 with porcine intestinal tissue following exposure to a Lactobacillus plantarum strain. The association of bacteria to host cells was examined by light microscopy and electron microscopy (EM) after appropriate treatments and staining, while changes in the proteome of porcine jejunal tissues were investigated using quantitative label-free proteomics. Exposure of porcine intestinal mucosal tissues to L. plantarum JC1 did not reduce the numbers of S. Typhimurium bacteria associating to the tissues but was associated with significant (P < 0.005) reductions in the percentages of areas of intestinal IVOC tissues giving positive staining results for acidic mucins. Conversely, the quantity of neutrally charged mucins present within the goblet cells of the IVOC tissues increased significantly (P < 0.05). In addition, tubulin- was expressed at high levels following inoculation of jejunal IVOC tissues with L. plantarum. Although L. plantarum JC1 did not reduce the association of S. Typhimurium strain SL1344 to the jejunal IVOC tissues, detection of increased acidic mucin secretion, host cytoskeletal rearrangements, and proteins involved in the porcine immune response demonstrated that this strain of L. plantarum may contribute to protecting the pig from infections by S. Typhimurium or other pathogens.

Long-term acclimation of leaf production, development, longevity and quality following 3 yr exposure to free-air CO2 enrichment during canopy closure in Populus

The effects of elevated CO2 on leaf development in three genotypes of Populus were investigated during canopy closure, following exposure to elevated CO2 over 3 yr using free-air enrichment.• Leaf quality was altered such that nitrogen concentration per unit d. wt (Nmass) declined on average by 22 and 13% for sun and shade leaves, respectively, in elevated CO2. There was little evidence that this was the result of ‘dilution’ following accumulation of nonstructural carbohydrates. Most likely, this was the result of increased leaf thickness. Specific leaf area declined in elevated CO2 on average by 29 and 5% for sun and shade leaves, respectively.• Autumnal senescence was delayed in elevated CO2 with a 10% increase in the number of days at which 50% leaf loss occurred in elevated as compared with ambient CO2.• These data suggest that changes in leaf quality may be predicted following long-term acclimation of fast-growing forest trees to elevated CO2, and that canopy longevity may increase, with important implications for forest productivity.

Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach

Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARalpha targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erbalpha pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erbalpha target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erbalpha pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations.

Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents

Parasitic infections cause a myriad of responses in their mammalian hosts, on immune as well as on metabolic level. A multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei-mouse, Trypanosoma brucei brucei-mouse, Schistosoma mansoni-mouse, and Fasciola hepatica-rat were statistically coanalyzed. 1H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected animals. Each parasite generated a unique metabolic signature in the host. Plasma cytokine concentrations were obtained using the ‘Meso Scale Discovery’ multi cytokine assay platform. Multivariate data integration methods were subsequently used to elucidate the component of the metabolic signature which is associated with inflammation and to determine specific metabolic correlates with parasite-induced changes in plasma cytokine levels. For example, the relative levels of acetyl glycoproteins extracted from the plasma metabolite profile in the P. berghei-infected mice were statistically correlated with IFN-γ, whereas the same cytokine was anticorrelated with glucose levels. Both the metabolic and the cytokine data showed a similar spatial distribution in principal component analysis scores plots constructed for the combined murine data, with samples from all infected animals clustering according to the parasite species and whereby the protozoan infections (P. berghei and T. b. brucei) grouped separately from the helminth infection (S. mansoni). For S. mansoni, the main infection-responsive cytokines were IL-4 and IL-5, which covaried with lactate, choline, and D-3-hydroxybutyrate. This study demonstrates that the inherently differential immune response to single and multicellular parasites not only manifests in the cytokine expression, but also consequently imprints on the metabolic signature, and calls for in-depth analysis to further explore direct links between immune features and biochemical pathways.

Processing empty categories in a second language: When naturalistic exposure fills the (intermediate) gap

An ongoing debate on second language (L2) processing revolves around whether or not L2 learners process syntactic information similarly to monolinguals (L1), and what factors lead to a native-like processing. According to the Shallow Structure Hypothesis (Clahsen & Felser, 2006a), L2 learners’ processing does not include abstract syntactic features, such as intermediate gaps of wh-movement, but relies more on lexical/semantic information. Other researchers have suggested that naturalistic L2 exposure can lead to native-like processing (Dussias, 2003). This study investigates the effect of naturalistic exposure in processing wh-dependencies. Twenty-six advanced Greek learners of L2 English with an average nine years of naturalistic exposure, 30 with classroom exposure, and 30 native speakers of English completed a self-paced reading task with sentences involving intermediate gaps. L2 learners with naturalistic exposure showed evidence of native-like processing of the intermediate gaps, suggesting that linguistic immersion can lead to native-like abstract syntactic processing in the L2.

Changes in liking for a no added salt soup as a function of exposure

Multiple exposures have been shown to increase preference for novel foods or flavours. This "mere exposure" effect is also well known anecdotally for changes in preference for tastants within foods, for example reducing sugar in tea or coffee. However, to date, this phenomenon has received little scientific attention. The present study addressed this issue in relation to changes in preference for salt within soup. Following an initial assessment of liking, familiarity and saltiness of six soups varying in salt content (0 - 337 mg NaCl/ml), thirty-seven participants, previously assessed for their preferred salt level in soup, were allocated to either an exposure group that received 20 ml soup samples with no added salt, to a group that received a 280 ml bowl of this soup, or to a control group that received 20 ml soup samples containing salt at 280mg/100g (within normal, commercial range). Soups were presented on eight occasions, at approximately daily intervals. The two groups receiving the no added salt soup showed increases in liking starting at the third exposure, and also evident in a repeat assessment following the exposures. Increases in familiarity of the no added salt soup were also evident during exposure. Rated saltiness of all soups increased as a function of exposure, so a change in saltiness perception could not account for changes in liking for just the no added salt soups. These data suggest that simple exposure to the taste of the no added salt soup was sufficient to increase liking to a level equivalent to the initially more preferred salt level.