mTORC2 Loss in Oligodendrocyte Progenitor Cells Results in Regional Hypomyelination in the Central Nervous System.

In the CNS, oligodendrocyte progenitor cells (OPCs) differentiate into mature oligodendrocytes to generate myelin, an essential component for normal nervous system function. OPC differentiation is driven by signaling pathways, such as mTOR, which functions in two distinct complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), containing Raptor or Rictor, respectively. In the current studies, mTORC2 signaling was selectively deleted from OPCs in PDGFRα-Cre X Rictorfl/fl mice. This study examined developmental myelination in male and female mice, comparing the impact of mTORC2 deletion in the corpus callosum and spinal cord. In both regions, Rictor loss in OPCs resulted in early reduction in myelin RNAs and proteins. However, these deficits rapidly recovered in spinal cord, where normal myelin was noted at P21 and P45. By contrast, the losses in corpus callosum resulted in severe hypomyelination and increased unmyelinated axons. The hypomyelination may result from decreased oligodendrocytes in the corpus callosum, which persisted in animals as old as postnatal day 350. The current studies focus on uniquely altered signaling pathways following mTORC2 loss in developing oligodendrocytes. A major mTORC2 substrate is phospho-Akt-S473, which was significantly reduced throughout development in both corpus callosum and spinal cord at all ages measured, yet this had little impact in spinal cord. Loss of mTORC2 signaling resulted in decreased expression of actin regulators, such as gelsolin in corpus callosum, but only minimal loss in spinal cord. The current study establishes a regionally specific role for mTORC2 signaling in OPCs, particularly in the corpus callosum.SIGNIFICANCE STATEMENT mTORC1 and mTORC2 signaling has differential impact on myelination in the CNS. Numerous studies identify a role for mTORC1, but deletion of Rictor (mTORC2 signaling) in late-stage oligodendrocytes had little impact on myelination in the CNS. However, the current studies establish that deletion of mTORC2 signaling from oligodendrocyte progenitor cells results in reduced myelination of brain axons. These studies also establish a regional impact of mTORC2, with little change in spinal cord in these conditional Rictor deletion mice. Importantly, in both brain and spinal cord, mTORC2 downstream signaling targets were impacted by Rictor deletion. Yet, these signaling changes had little impact on myelination in spinal cord, while they resulted in long-term alterations in myelination in brain.

Sediment Spatial Distribution and Quality Assessment of Metals in Chinook Salmon and Resident Killer Whale Marine Habitat in British Columbia, Canada.

At-risk resident killer whale (Orcinus orca) populations of the northeastern Pacific, Canada, and their main prey, Chinook Salmon (Oncorhynchus tshawytscha), are exposed to a variety of contaminants including chemical elements from both natural and anthropogenic sources, which may be constraining their recovery. Concentrations of 36 chemical elements in subtidal surface sediments (1-435 m depth) collected from 98 sites along the British Columbia coast were used to characterize coast-wide patterns, and a subset of metals (mercury (Hg), cadmium (Cd), arsenic (As), nickel (Ni), copper (Cu), and lead (Pb)) were selected to assess Chinook Salmon and resident killer whale marine habitat quality. Principal component analysis (PCA) showed a dominance of Hg, antimony (Sb), Pb, Cu, and zinc (Zn) for Prince Rupert Harbour, Victoria Harbour, and Burrard Inlet, suggesting local sources. Based on the PCA, geochemical properties such as total organic carbon (TOC), acid volatile sulfide (AVS), and pH explained the spatial distribution of all elements in sediment (p < 0.001). Mercury, Cd, As, Ni, Cu, and Pb hotspots were identified along the coast of Vancouver Island, the central and north coast, in the Strait of Georgia, and Haida Gwaii. Bischof Island of Haida Gwaii and Ardmillan Bay on the central coast were most contaminated and enriched by Cd, determined by geoaccumulation index (Igeo) and enrichment factor (EF), respectively. Marine habitat quality was assessed by comparing metal concentrations to Canadian Sediment Quality Guidelines (SQGs). Chinook Salmon populations may be indirectly affected by metal toxicity (As > Cd and Cu > Ni > Hg > Pb) to lower trophic level prey species. Toxicity related impacts to benthic organisms as a result of exposure to elevated Cd and As concentrations in Northern Resident Killer Whale critical habitat and to Hg, Cd, As, Ni, Cu, and Pb concentrations in Southern Resident Killer Whale critical habitat may indirectly pose a threat to resident killer whale populations, highlighting a need for management actions to reduce risks associated with these metals.

PAK1 Positively Regulates Oligodendrocyte Morphology and Myelination.

The actin cytoskeleton is crucial for oligodendrocyte differentiation and myelination. Here we show that p21-activated kinase 1 (PAK1), a well-known actin regulator, promotes oligodendrocyte morphologic change and myelin production in the CNS. A combination of in vitro and in vivo models demonstrated that PAK1 is expressed throughout the oligodendrocyte lineage with highest expression in differentiated oligodendrocytes. Inhibiting PAK1 early in oligodendrocyte development decreased oligodendrocyte morphologic complexity and altered F-actin spreading at the tips of oligodendrocyte progenitor cell processes. Constitutively activating AKT in oligodendrocytes in male and female mice, which leads to excessive myelin wrapping, increased PAK1 expression, suggesting an impact of PAK1 during active myelin wrapping. Furthermore, constitutively activating PAK1 in oligodendrocytes in zebrafish led to an increase in myelin internode length while inhibiting PAK1 during active myelination decreased internode length. As myelin parameters influence conduction velocity, these data suggest that PAK1 may influence communication within the CNS. These data support a model in which PAK1 is a positive regulator of CNS myelination.SIGNIFICANCE STATEMENT Myelin is a critical component of the CNS that provides metabolic support to neurons and also facilitates communication between cells in the CNS. Recent data demonstrate that actin dynamics drives myelin wrapping, but how actin is regulated during myelin wrapping is unknown. The authors investigate the role of the cytoskeletal modulator PAK1 during differentiation and myelination by oligodendrocytes, the myelinating cells of the CNS. They demonstrate that PAK1 promotes oligodendrocyte differentiation and myelination by modulating the cytoskeleton and thereby internode length, thus playing a critical role in the function of the CNS.

Mechanistic Target of Rapamycin Regulates the Oligodendrocyte Cytoskeleton during Myelination.

During differentiation, oligodendrocyte precursor cells (OPCs) extend a network of processes that make contact with axons and initiate myelination. Recent studies revealed that actin polymerization is required for initiation of myelination whereas actin depolymerization promotes myelin wrapping. Here, we used primary OPCs in culture isolated from neonatal rat cortices of both sexes and young male and female mice with oligodendrocyte-specific deletion of mechanistic target of rapamycin (mTOR) to demonstrate that mTOR regulates expression of specific cytoskeletal targets and actin reorganization in oligodendrocytes during developmental myelination. Loss or inhibition of mTOR reduced expression of profilin2 and ARPC3, actin polymerizing factors, and elevated levels of active cofilin, which mediates actin depolymerization. The deficits in actin polymerization were revealed in reduced phalloidin and deficits in oligodendrocyte cellular branching complexity at the peak of morphologic differentiation and a delay in initiation of myelination. We further show a critical role for mTOR in expression and localization of myelin basic protein (Mbp) mRNA and MBP protein to the cellular processes where it is necessary at the myelin membrane for axon wrapping. Mbp mRNA transport deficits were confirmed by single molecule RNA FISH. Moreover, expression of the kinesin family member 1B, an Mbp mRNA transport protein, was reduced in CC1+ cells in the mTOR cKO and in mTOR inhibited oligodendrocytes undergoing differentiation in vitro These data support the conclusion that mTOR regulates both initiation of myelination and axon wrapping by targeting cytoskeletal reorganization and MBP localization to oligodendrocyte processes.SIGNIFICANCE STATEMENT Myelination is essential for normal CNS development and adult axon preservation and function. The mechanistic target of rapamycin (mTOR) signaling pathway has been implicated in promoting CNS myelination; however, there is a gap in our understanding of the mechanisms by which mTOR promotes developmental myelination through regulating specific downstream targets. Here, we present evidence that mTOR promotes the initiation of myelination through regulating specific cytoskeletal targets and cellular process expansion by oligodendrocyte precursor cells as well as expression and cellular localization of myelin basic protein.

Characterization of the microbiome and immune response in corals with chronic Montipora white syndrome.

Coral diseases have increased in frequency and intensity around the tropics worldwide. However, in many cases, little is known about their etiology. Montipora white syndrome (MWS) is a common disease affecting the coral Montipora capitata, a major reef builder in Hawai'i. Chronic Montipora white syndrome (cMWS) is a slow-moving form of the disease that affects M. capitata throughout the year. The effects of this chronic disease on coral immunology and microbiology are currently unknown. In this study, we use prophenoloxidase immune assays and 16S rRNA gene amplicon sequencing to characterize the microbiome and immunological response associated with cMWS. Our results show that immunological and microbiological responses are highly localized. Relative to diseased samples, apparently healthy portions of cMWS corals differed in immune activity and in the relative abundance of microbial taxa. Coral tissues with cMWS showed decreased tyrosinase-type catecholase and tyrosinase-type cresolase activity and increased laccase-type activity. Catecholase and cresolase activity were negatively correlated across all tissue types with microbiome richness. The localized effect of cMWS on coral microbiology and immunology is probably an important reason for the slow progression of the disease. This local confinement may facilitate interventions that focus on localized treatments on tissue types. This study provides an important baseline to understand the interplay between the microbiome and immune system and the mechanisms used by corals to manage chronic microbial perturbations associated with white syndrome.

Complexity Matching: Brain Signals Mirror Environment Information Patterns during Music Listening and Reward.

Understanding how the human brain integrates information from the environment with intrinsic brain signals to produce individual perspectives is an essential element of understanding the human mind. Brain signal complexity, measured with multiscale entropy, has been employed as a measure of information processing in the brain, and we propose that it can also be used to measure the information available from a stimulus. We can directly assess the correspondence between brain signal complexity and stimulus complexity as an indication of how well the brain reflects the content of the environment in an analysis that we term "complexity matching." Music is an ideal stimulus because it is a multidimensional signal with a rich temporal evolution and because of its emotion- and reward-inducing potential. When participants focused on acoustic features of music, we found that EEG complexity was lower and more closely resembled the musical complexity compared to an emotional task that asked them to monitor how the music made them feel. Music-derived reward scores on the Barcelona Music Reward Questionnaire correlated with less complexity matching but higher EEG complexity. Compared with perceptual-level processing, emotional and reward responses are associated with additional internal information processes above and beyond those linked to the external stimulus. In other words, the brain adds something when judging the emotional valence of music.

The Actin Cytoskeleton in Myelinating Cells.

Myelinating cells of both the peripheral and central nervous systems (CNSs) undergo dramatic cytoskeletal reorganization in order to differentiate and produce myelin. Myelinating oligodendrocytes in the CNS show a periodic actin pattern, demonstrating tight regulation of actin. Furthermore, recent data demonstrate that actin polymerization drives early cell differentiation and that actin depolymerization drives myelin wrapping. Dysregulation of the actin cytoskeleton in myelinating cells is seen in some disease states. This review highlights the cytoskeletal molecules that regulate differentiation of and myelination by cells of the PNS and CNS, informing our understanding of neural development, in particular myelination.

The contribution of qualitative research within the PRECISE study in sub-Saharan Africa.

The PRECISE Network is a cohort study established to investigate hypertension, fetal growth restriction and stillbirth (described as "placental disorders") in Kenya, Mozambique and The Gambia. Several pregnancy or birth cohorts have been set up in low- and middle-income countries, focussed on maternal and child health. Qualitative research methods are sometimes used alongside quantitative data collection from these cohorts. Researchers affiliated with PRECISE are also planning to use qualitative methods, from the perspective of multiple subject areas. This paper provides an overview of the different ways in which qualitative research methods can contribute to achieving PRECISE's objectives, and discusses the combination of qualitative methods with quantitative cohort studies more generally.We present planned qualitative work in six subject areas (health systems, health geography, mental health, community engagement, the implementation of the TraCer tool, and respectful maternity care). Based on these plans, with reference to other cohort studies on maternal and child health, and in the context of the methodological literature on mixed methods approaches, we find that qualitative work may have several different functions in relation to cohort studies, including informing the quantitative data collection or interpretation. Researchers may also conduct qualitative work in pursuit of a complementary research agenda. The degree to which integration between qualitative and quantitative methods will be sought and achieved within PRECISE remains to be seen. Overall, we conclude that the synergies resulting from the combination of cohort studies with qualitative research are an asset to the field of maternal and child health.

Continuous exposure to mercury during embryogenesis and chick development affects later survival and reproduction of zebra finch (Taeniopygia guttata).

Methylmercury (MeHg) is a global environmental contaminant that bioaccumulates and has multiple toxic modes of action. Aquatic species have traditionally been the focus of wildlife toxicological research on mercury, but terrestrial organisms, including passerine birds, can be exposed to similarly elevated levels of MeHg. In this study we exposed a model passerine, the zebra finch (Taeniopygia guttata), to MeHg in ovo, as chicks only, or with a combined 'in ovo + chick' treatment. We isolated exposure to specific developmental stages through the use of egg injections (3.2 µg Hg/g egg) and controlled oral dosing of chicks (0.24 µg Hg/g bw/day from day 1 to day 30). In ovo exposure to MeHg reduced hatching success, but there was no effect of MeHg on chick growth. We found that in ovo only or chick only exposure did not have long-term effects, but there was some evidence for longer-term effects of combined 'in ovo + chick' exposure on post-fledging survival and potentially sex-biased survival which resulted in very few 'in ovo + chick' exposed females surviving to breed. These females also had lower overall breeding productivity that was mainly due to lower hatching success of their offspring, not lower chick-rearing success. We found no effect of treatment on clutch size or latency to laying among females that did lay eggs. Our study suggests that combined embryonic and nestling MeHg exposure has compounding latent effects on productivity, likely through a mechanism that influences the ability of females to lay fertile eggs that hatch.

Evidence-based systematic review of cognitive rehabilitation, emotional, and family treatment studies for children with acquired brain injury literature: From 2006 to 2017.

This paper updates guidelines for effective treatments of children with specific types of acquired brain injury (ABI) published in 2007 with more recent evidence. A systematic search was conducted for articles published from 2006 to 2017. Full manuscripts describing treatments of children (post-birth to 18) with acquired brain injury were included if study was published in peer-reviewed journals and written in English. Two independent reviewers and a third, if conflicts existed, evaluated the methodological quality of studies with an Individual Study Review Form and a Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Strength of study characteristics was used in development of practice guidelines. Fifty-six peer-reviewed articles, including 27 Class I studies, were included in the final analysis. Established guidelines for writing practice recommendations were used and 22 practice recommendations were written with details of potential treatment limitations. There was strong evidence for family/caregiver-focused interventions, as well as direct interventions to improve attention, memory, executive functioning, and emotional/behavioural functioning. A majority of the practice standards and guidelines provided evidence for the use of technology in delivery of interventions, representing an important trend in the field.

Online Family Problem Solving for Pediatric Traumatic Brain Injury: Influences of Parental Marital Status and Participation on Adolescent Outcomes.

OBJECTIVE: To examine the moderating effects of parent marital status and participation on efficacy of an online family problem-solving intervention for pediatric traumatic brain injury (TBI). METHODS: Participants were 132 adolescents (12-17 years) who had sustained a recent (<6 months) TBI and their parents. Participants were randomly assigned to the intervention (Counselor-Assisted Problem Solving, CAPS) or an Internet resource comparison (IRC) condition. CAPS was designed to support families in the initial phase following TBI, by teaching problem-solving skills and addressing common challenges. To examine the moderating effect of parent marital status, participants were divided into 4 groups (ie, CAPS married household, CAPS unmarried household, IRC married household, and IRC unmarried household). Family income and caregiver education were controlled in analyses. RESULTS: Parent marital status moderated treatment effects on adolescent externalizing behavior problems. Adolescents from married households in CAPS displayed fewer behavior problems at 6 and 18 months postbaseline compared with adolescents from unmarried households in CAPS. Among married CAPS families, there were no differences in outcomes among families where 1 or 2 parents actively participated. CONCLUSIONS: Web-based interventions for pediatric TBI, such as CAPS, are a viable option for some although not all families. Further research is needed to investigate factors that influence efficacy to match families to the most beneficial treatments.

Deepwater Horizon crude oil impacts the developing hearts of large predatory pelagic fish.

The Deepwater Horizon disaster released more than 636 million L of crude oil into the northern Gulf of Mexico. The spill oiled upper surface water spawning habitats for many commercially and ecologically important pelagic fish species. Consequently, the developing spawn (embryos and larvae) of tunas, swordfish, and other large predators were potentially exposed to crude oil-derived polycyclic aromatic hydrocarbons (PAHs). Fish embryos are generally very sensitive to PAH-induced cardiotoxicity, and adverse changes in heart physiology and morphology can cause both acute and delayed mortality. Cardiac function is particularly important for fast-swimming pelagic predators with high aerobic demand. Offspring for these species develop rapidly at relatively high temperatures, and their vulnerability to crude oil toxicity is unknown. We assessed the impacts of field-collected Deepwater Horizon (MC252) oil samples on embryos of three pelagic fish: bluefin tuna, yellowfin tuna, and an amberjack. We show that environmentally realistic exposures (1-15 µg/L total PAH) cause specific dose-dependent defects in cardiac function in all three species, with circulatory disruption culminating in pericardial edema and other secondary malformations. Each species displayed an irregular atrial arrhythmia following oil exposure, indicating a highly conserved response to oil toxicity. A considerable portion of Gulf water samples collected during the spill had PAH concentrations exceeding toxicity thresholds observed here, indicating the potential for losses of pelagic fish larvae. Vulnerability assessments in other ocean habitats, including the Arctic, should focus on the developing heart of resident fish species as an exceptionally sensitive and consistent indicator of crude oil impacts.

Indicators of Marine Pollution in the North Pacific Ocean.

The complex nature of ocean pollution underscores the utility in identifying and characterizing a limited number of "indicators" that enables scientists and managers to track trends over space and time. This paper introduces a special issue on indicators of marine pollution in the North Pacific Ocean and builds on a scientific session that was held at the North Pacific Marine Science Organization. The special issue highlights studies using a variety of indicators to provide insight into the identification of legacy and emerging contaminants, the ranking of priority pollutants from various sources, and the effects of contaminants on ecosystem health in the North Pacific Ocean. Examples include the use of mussels to illustrate spatial and temporal trends of a number of contaminants following the 2011 tsunami in Japan, the use of molecular marker (linear alkylbenzenes, hopanes, and polycyclic aromatic hydrocarbons) profiles to identify pollution sources, and the use of plastic resin pellets to illustrate spatial trends of petroleum pollution around the world. Stable isotopes were used to strengthen the utility of the Glaucous-winged gull (Larus glaucescens) as an indicator of marine pollution. Examples also demonstrate the development and application of biomarker approaches, including gene transcripts, oxidative stress, estradiol, hatchability, and respiration and swimming behavior abnormalities, as a function of exposure to polychlorinated biphenyls, sulfur-diesel, Pinghu crude oil, galaxolide and antifouling biocides. We provide a brief review of indicators of marine pollution, identify research gaps, and summarize key findings from the articles published within the issue. This special issue represents the first compilation of research pertaining to marine pollution indicators in the North Pacific Ocean and provides guidance to inform mitigation and monitoring efforts of contaminants in the region.

Spatial and temporal variation of an ice-adapted predator's feeding ecology in a changing Arctic marine ecosystem.

Spatial and temporal variation can confound interpretations of relationships within and between species in terms of diet composition, niche size, and trophic position (TP). The cause of dietary variation within species is commonly an ontogenetic niche shift, which is a key dynamic influencing community structure. We quantified spatial and temporal variations in ringed seal (Pusa hispida) diet, niche size, and TP during ontogeny across the Arctic-a rapidly changing ecosystem. Stable carbon and nitrogen isotope analysis was performed on 558 liver and 630 muscle samples from ringed seals and on likely prey species from five locations ranging from the High to the Low Arctic. A modest ontogenetic diet shift occurred, with adult ringed seals consuming more forage fish (approximately 80 versus 60 %) and having a higher TP than subadults, which generally decreased with latitude. However, the degree of shift varied spatially, with adults in the High Arctic presenting a more restricted niche size and consuming more Arctic cod (Boreogadus saida) than subadults (87 versus 44 %) and adults at the lowest latitude (29 %). The TPs of adult and subadult ringed seals generally decreased with latitude (4.7-3.3), which was mainly driven by greater complexity in trophic structure within the zooplankton communities. Adult isotopic niche size increased over time, likely due to the recent circumpolar increases in subarctic forage fish distribution and abundance. Given the spatial and temporal variability in ringed seal foraging ecology, ringed seals exhibit dietary plasticity as a species, suggesting adaptability in terms of their diet to climate change.

Sequential Evolution of Vancomycin-Intermediate Resistance Alters Virulence in Staphylococcus aureus: Pharmacokinetic/Pharmacodynamic Targets for Vancomycin Exposure.

Staphylococcus aureus possesses exceptional virulence and a remarkable ability to adapt in the face of antibiotic therapy. We examined the in vitro evolution of S. aureus in response to escalating vancomycin exposure by evaluating bacterial killing and the progression of resistance. A hollow-fiber infection model was utilized to simulate human doses of vancomycin increasing from 0.5 to 4 g every 12 h (q12h) versus a high inoculum (10(8) CFU/ml) of methicillin-resistant S. aureus (MRSA) USA300 and USA400. Host-pathogen interactions using Galleria mellonella and accessory gene regulator (agr) expression were studied in serially obtained isolates. In both USA300 and USA400 MRSA isolates, vancomycin exposure up to 2 g q12h resulted in persistence and regrowth, whereas 4 g administered q12h achieved sustained killing against both strains. As vancomycin exposure increased from 0.5 to 2 g q12h, the bacterial population shifted toward vancomycin-intermediate resistance, and collateral increases in the MICs of daptomycin and televancin were observed over 10 days. Guideline-recommended exposure of a ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC ratio) of 200 displayed a 0.344-log bacterial reduction in area, whereas fAUC/MICs of 371 and 554 were needed to achieve 1.00- and 2.00-log reductions in area, respectively. The stepwise increase in resistance paralleled a decrease in G. mellonella mortality (P = 0.021) and a gradual decline of RNAIII expression over 10 days. Currently recommended doses of vancomycin resulted in amplification of resistance and collateral damage to other antibiotics. Decreases in agr expression and virulence during therapy may be an adaptive mechanism of S. aureus persistence.

Long-Term Caregiver Mental Health Outcomes Following a Predominately Online Intervention for Adolescents With Complicated Mild to Severe Traumatic Brain Injury.

OBJECTIVE: To examine the efficacy of counselor-assisted problem solving (CAPS) in improving long-term caregiver psychological functioning following traumatic brain injury (TBI) in adolescents. METHODS: This randomized clinical trial compared CAPS (n = 65), a predominantly online problem-solving intervention, with an Internet resource comparison (n = 67) program. Families of adolescents with TBI completed a baseline assessment and follow-up assessments 6, 12, and 18 months later. General linear mixed models were used to examine longitudinal changes in caregiver global psychological distress, depressive symptoms, and caregiving self-efficacy. Family income and injury severity were examined as moderators of treatment efficacy. RESULTS: Family income moderated long-term changes in caregiver psychological distress. For lower-income caregivers, the CAPS intervention was associated with lower levels of psychological distress at 6, 12, and 18 months post baseline. CONCLUSIONS: These findings support the utility of Web-based interventions in improving long-term caregiver psychological distress, particularly for lower-income families.

Factors influencing attrition in a multisite, randomized, clinical trial following traumatic brain injury in adolescence.

BACKGROUND: Attrition in longitudinal research negatively affects statistical power, disrupts statistical stability, and can produce unwanted bias. OBJECTIVE: To investigate factors associated with shorter length of study participation and lower rates of study completion (ie, attrition) in a large, multisite, longitudinal, randomized, clinical trial examining the efficacy of a Web-based family problem-solving treatment following traumatic brain injury (TBI) in adolescence. SETTING: Five major trauma centers in the central and western regions of the United States. PARTICIPANTS: Children (N = 132) aged 12 to 17 years hospitalized for complicated mild to severe TBI within the previous 6 months. RESULTS: Completers had a higher primary caregiver education and higher family income than noncompleters, whereas ethnicity, latency to baseline assessment, and intervention group were not significantly associated with study completion. CONCLUSION: This is the first study that has specifically examined factors of attrition in a pediatric TBI population. The results suggest that research on pediatric TBI populations may be biased toward higher-income families and highlights the importance of designing studies with increased awareness of the impact of participant demographic factors.

Satellite telemetry informs PCB source apportionment in a mobile, high trophic level marine mammal: the ringed seal (Pusa hispida).

Marine mammals are typically poor indicators of point sources of environmental contaminants as a consequence of their often complex feeding ecologies and extensive movements, all of which mask the contributions of specific inputs. The release of polychlorinated biphenyls (PCBs) by a military radar station into Saglek Bay, Labrador (Canada) has contaminated marine sediments, bottom-feeding fish, seabirds, and some ringed seals, but attributing the PCBs in the latter highly mobile animals to this source is exceedingly difficult. In addition to the application of such tools as stable isotopes (δ(15)N and δ(13)C) and univariate and multivariate statistical exploration of contaminant patterns and ratios, we used satellite telemetry to track the movements of 13 seals in their transient use of different feeding areas. Reduced size of home range and core area (i.e., areas of concentrated use), as well as increased time in coastal inlets, were important determinants of increased PCB concentrations in seals reflecting the contribution of Saglek Bay. Seals were classified into the same feeding groups using both space use and their contaminant burdens 85% of the time, highlighting the link between feeding ecology and exposure to PCBs. While the PCB source at Saglek provided a strong local signal in a remote environment, this first use of satellite telemetry demonstrates the utility of evaluating space-use strategies to better understand contaminant exposure, and more specifically the contribution of contaminant hotspots to mobile predators.

PCB related effects thresholds as derived through gene transcript profiles in locally contaminated ringed seals (Pusa hispida).

Causal evidence linking toxic injury to polychlorinated biphenyl (PCB) exposure is typically confounded by the complexity of real-world contaminant mixtures to which aquatic wildlife are exposed. A local PCB "hotspot" on the Labrador coast provided a rare opportunity to evaluate the effects of PCBs on the health of a marine mammal as this chemical dominated their persistent organic pollutant (POP) burdens. The release of approximately 260 kg of PCBs by a military radar facility over a 30 year period (1970-2000) contaminated some local marine biota, including the ringed seal (Pusa hispida). The abundance profiles of eight health-related gene transcripts were evaluated in liver samples collected from 43 ringed seals in the affected area. The mRNA transcript levels of five gene targets, including aryl hydrocarbon receptor (Ahr), interleukin-1 ß (Il1b), estrogen receptor α (Esr1), insulin like growth factor receptor 1 (Igf1), and glucocorticoid receptor α (Nr3c1) correlated with increasing levels of blubber PCBs. PCB threshold values calculated using best-fit hockey-stick regression models for these five genes averaged 1,680±206 ng/g lw, with the lowest, most conservative, being 1,370 ng/g lw for Il1b. Approximately 14% of the seals in the region exceeded this threshold. The dominance of PCBs in the seals studied enabled an assessment of the effects of this chemical on gene transcripts involved in regulating the health of a highly mobile predator, something that is rarely possible in the world of complex mixtures.

Parent psychological functioning and communication predict externalizing behavior problems after pediatric traumatic brain injury.

OBJECTIVE: Adolescents sustaining traumatic brain injury (TBI) show increased prevalence of behavior problems. This study investigated the associations of parent mental health, family functioning, and parent-adolescent interaction with adolescent externalizing behavior problems in the initial months after TBI, and examined whether injury severity moderated these associations. METHODS: 117 parent-adolescent dyads completed measures of family functioning, adolescent behavior, and parent mental health an average of 108 days post-TBI. Dyads also engaged in a 10-min video-recorded problem-solving activity coded for parent behavior and tone of interaction. RESULTS: Overall, higher ratings of effective parent communication were associated with fewer externalizing behavior problems, whereas poorer caregiver psychological functioning was associated with greater adolescent externalizing behaviors. Results failed to reveal moderating effects of TBI severity on the relationship between socio-environmental factors and behavior problems. CONCLUSIONS: Interventions targeting parent communication and/or improving caregiver psychological health may ameliorate potential externalizing behavior problems after adolescent TBI.