Assessing the effects of chemical mixtures using a Bayesian network-relative risk model (BN-RRM) integrating adverse outcome pathways (AOPs) in three Puget Sound watersheds

Chemical mixtures are difficult to assess at the individual level, but more challenging at the population level. There is still little insight of the molecular pathway for numerous chemical mixtures. We have conducted a regional-scale ecological risk assessment by evaluating the effects chemical mixtures to populations with a Bayesian Network- Relative Risk Model (BN-RRM) incorporating a molecular pathway. We used this BN-RRM framework in a case study with organophosphate pesticide (OP) mixtures (diazinon, chlorpyrifos, and malathion) in three watersheds (Lower Skagit, Nooksack, Cedar) in the state of Washington (USA). Puget Sound Chinook salmon (Oncorhynchus tshawytscha) Evolutionary Significant Units (ESU) were chosen as population endpoints. These populations are a valuable ecosystem service in the Pacific Northwest because they benefit the region as a species that provide protection of biodiversity and are spiritually and culturally treasured by the local tribes. Laetz et al. (2009, 2013) indicated that organophosphate pesticide mixtures act synergistically to salmon and impair neurological molecular activity which leads to a change in swimming behavior and mortality, which then leads to changes in population productivity. Exposure response curves were generated for OP mixtures to connect the molecular pathway. Ecological stressors from dissolved oxygen and temperature were also included in our risk analysis. Synergism within the mixtures as well as increasing temperature and decreasing dissolve oxygen content lead to increasing risk to Puget Sound Chinook salmon populations. This research demonstrates a probabilistic approach with a multiple stressor framework to estimate the effects of mixtures through a molecular pathway and predict impacts to these valuable ecosystem services

Dissecting a complex chemical stress: chemogenomic profiling of plant hydrolysates.

The efficient production of biofuels from cellulosic feedstocks will require the efficient fermentation of the sugars in hydrolyzed plant material. Unfortunately, plant hydrolysates also contain many compounds that inhibit microbial growth and fermentation. We used DNA-barcoded mutant libraries to identify genes that are important for hydrolysate tolerance in both Zymomonas mobilis (44 genes) and Saccharomyces cerevisiae (99 genes). Overexpression of a Z. mobilis tolerance gene of unknown function (ZMO1875) improved its specific ethanol productivity 2.4-fold in the presence of miscanthus hydrolysate. However, a mixture of 37 hydrolysate-derived inhibitors was not sufficient to explain the fitness profile of plant hydrolysate. To deconstruct the fitness profile of hydrolysate, we profiled the 37 inhibitors against a library of Z. mobilis mutants and we modeled fitness in hydrolysate as a mixture of fitness in its components. By examining outliers in this model, we identified methylglyoxal as a previously unknown component of hydrolysate. Our work provides a general strategy to dissect how microbes respond to a complex chemical stress and should enable further engineering of hydrolysate tolerance

Tailoring exciton diffusion and domain size in photovoltaic small molecules by processing

Funding: European Research Council (grant 321305); UK EPSRC for equipment grant (EP/L017008/1) and (EP/M508214/1) (OB).Exciton diffusion is an important part of light harvesting in organic photovoltaics (OPVs) because it enables excitons to reach the interface betweeen donor and acceptor and contribute to the photocurrent. Here we used simple and cost-effective techniques of thermal annealing and solvent vapour annealing to increase the exciton diffusion coefficient and exciton diffusion length in two liquid crystalline electron donor materials BQR and BTR. We found that the three-dimensional exciton diffusion length increased to ~40 nm upon annealing in both materials. Grazing-incidence wide angle X-ray scattering (GIWAXS) measurements show an increase of crystallite size to ~37 nm in both materials after thermal annealing. We determined an average domain size of these materials in the blends with PC71BM using diffusion-limited fluorescence quenching and found that it increased to 31 nm in BTR PC71BM blends and to 60 nm in BQR PC71BM blends. Our results provide understanding of how annealing improves device efficiency.PostprintPeer reviewe

Peer Influence and Nonsuicidal Self Injury: Longitudinal Results in Community and Clinically-Referred Adolescent Samples

Research suggests that adolescents' engagement in nonsuicidal self-injurious (NSSI) behaviors may be increasing over time, yet little is known regarding distal longitudinal factors that may promote engagement in these behaviors. Data from two longitudinal studies are presented to examine whether NSSI may be associated with peer influence processes. Study 1 included 377 adolescents from a community-based sample; Study 2 included 140 clinically-referred adolescents recruited from a psychiatric inpatient facility. In Study 1, adolescents' NSSI was examined at baseline and one year later. Adolescents' nominated best friend reported their own levels of NSSI. In Study 2, adolescents' NSSI was examined at baseline as well as 9 and 18-months post-baseline. Adolescents' perceptions of their friends' engagement in self-injurious behavior (including suicidality) and depressed mood also were examined at all three time points. Baseline depressive symptoms were measured in both studies; gender and age were examined as moderators of peer influence effects. Results from both studies supported longitudinal peer socialization effects of friends' self-injurious behavior on adolescents' own NSSI for girls, but not for boys, even after controlling for depressive symptoms as a predictor. Study 1 suggested socialization effects mostly for younger youth. Results from Study 2 also suggested longitudinal socialization effects, as well as peer selection effects; adolescents' NSSI was associated with increasing perceptions of their friends' engagement in depressive/self-injurious thoughts and behavior. Findings contribute to the nascent literature on longitudinal predictors of NSSI and to work on peer influence

Using metapopulation models to estimate the effects of pesticides and environmental stressors to Spring Chinook salmon in the Yakima River Basin, WA

Population-level endpoints provide ecological relevance to Ecological Risk Assessments (ERAs), because this is the level at which environmental management decisions are made. However, many population-level risk assessments do not reflect the spatial and temporal heterogeneity of the populations they represent, and thus preclude an understanding of how population dynamics and viability are affected by toxicants on a regional scale. We have developed a probabilistic ERA (specifically, a Bayesian Network-Relative Risk Model (BN-RRM)) that integrates an Adverse Outcome Pathway (AOP) framework, to quantify the sub-lethal and lethal effects of toxicants and environmental stressors on the metapopulation dynamics of salmonids. As a case study for developing this model, we have examined the impacts of organophosphate (OP) insecticides, water temperature, and dissolved oxygen on the Spring Chinook (Oncorhynchus tshawytscha) salmon metapopulation in the Yakima River Basin (YRB), Washington. A stochastic Matrix Metapopulation Model was developed using demographic data for three Spring Chinook salmon populations and one supplemental hatchery population in the YRB. Site specific data on OP contaminated habitats utilized by various salmonid life stages were incorporated into the metapopulation model by incrementally reducing survival parameters based on levels of exposure. Exposure scenarios were simulated for 200 replications of 50-year population projections using RAMAS Metapop©, and the results were incorporated into the BN-RRM. The results of this modeling effort indicated that small, wild Spring Chinook populations in the YRB have a greater probability of altered population dynamics when exposed to stressors than larger, supplemented populations. Additionally, the results indicated a seasonal effect of the stressors, with summer conditions posing a greater risk to salmon populations than winter conditions. This probabilistic ERA framework shows promise for estimating the spatiotemporal impacts of stressors on ESA-listed species (i.e., Pacific salmon) at the metapopulation level, where population dynamics and spatial structure create complex risk dynamics

Assessing the Effects of Chemical Mixtures using a Bayesian Network-Relative Risk Model (BN-RRM) Integrating Adverse Outcome Pathways (AOPs)

There are long-standing uncertainties about toxicity of chemical mixtures to populations. Laboratory toxicity tests have confirmed synergistic and antagonistic effects to individuals, but not to populations.We will conduct a regional scale ecological risk assessment by evaluating the effects chemical mixtures to populations with a new Bayesian Network- Relative Risk Model (BN-RRM) incorporating an Adverse Outcome Pathway (AOP). We started applying this new BN-RRM framework in a case study with organophosphate pesticide mixtures (diazinon, chlorpyrifos, and malathion). Acetylcholinesterase inhibition (AChE) was chosen the molecular initiating event and the Puget Sound Chinook salmon (Oncorhynchus tshawytscha) and Coho salmon (Oncorhynchus kisutch) Evolutionary Significant Units (ESU) were chosen as population endpoints. Dose-response equations will be generated from the mixtures, integrated into the new BN-RRM framework and then overall risk will be calculated for the populations. Preliminary results indicate that organophosphate pesticide mixtures act synergistically and impair olfactory function that lead to loss of antipredator, homing and reproductive behavior which lead to changes in population age structure and patch dynamics. Assessing mixtures through this new BN-RRM framework is an innovative method of predicting effects to populations. This research will demonstrate a probabilistic approach to synthesize the effects of mixtures and predict impacts to populations

The Lantern Vol. 5, No. 1, December 1936

• All of Us • Public Dance • In Tibet, of All Places • Thoughts • Subterranean Conflict on the Campus • Out, Out Into Fragrance and Sweetness • My Soul Steals Out to Meet You In the Night • Bored Young Lady • Guay Shin\u27s Prayer • On Playing Ping-Pong • The Love-Life of One Cat and the Death of Another • My Lady • Danger! Germs Working! • The Wolves • Letters from India • With Apologies to Hamlet • The Dreamhttps://digitalcommons.ursinus.edu/lantern/1015/thumbnail.jp

Increased ventral striatal volume in college-aged binge drinkers

BACKGROUND Binge drinking is a serious public health issue associated with cognitive, physiological, and anatomical differences from healthy individuals. No studies, however, have reported subcortical grey matter differences in this population. To address this, we compared the grey matter volumes of college-age binge drinkers and healthy controls, focusing on the ventral striatum, hippocampus and amygdala. METHOD T1-weighted images of 19 binge drinkers and 19 healthy volunteers were analyzed using voxel-based morphometry. Structural data were also covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Cluster-extent threshold and small volume corrections were both used to analyze imaging data. RESULTS Binge drinkers had significantly larger ventral striatal grey matter volumes compared to controls. There were no between group differences in hippocampal or amygdalar volume. Ventral striatal, amygdalar, and hippocampal volumes were also negatively related to AUDIT scores across groups. CONCLUSIONS Our findings stand in contrast to the lower ventral striatal volume previously observed in more severe forms of alcohol use disorders, suggesting that college-age binge drinkers may represent a distinct population from those groups. These findings may instead represent early sequelae, compensatory effects of repeated binge and withdrawal, or an endophenotypic risk factor

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions