Mental Health Problems in Adolescence and the Interpretation of Unambiguous Threat

Aberrant threat perception has been linked to paranoia, anxiety and other mental health problems, and is widely considered to be a core, transdiagnostic feature of psychopathology. However, to date there has been only limited investigation of whether mental health problems are associated with a biased interpretation of stimuli that have explicit (as opposed to ambiguous) connotations of threat. In the present study, 41 adolescents diagnosed with a mental illness and 45 demographically matched controls were asked to provide danger ratings of stimuli normatively rated as being either low or high in potential threat. All participants were also asked to complete background measures of cognitive function, mental health and wellbeing. The results indicated that the two groups did not differ in their capacity to discriminate between low and high threat stimuli, nor did they differ in the absolute level of threat that they attributed to these stimuli. However, for the control group, the overall level of threat perceived in facial stimuli was correlated with two important indices of mental health (depression and anxiety). No associations emerged in the clinical group. These data are discussed in relation to their potential implications for the role of aberrant threat perception in transdiagnostic models of mental health.     

Priming Effects in Boreal Black Spruce Forest Soils: Quantitative Evaluation and Sensitivity Analysis

Laboratory studies show that introduction of fresh and easily decomposable organic carbon (OC) into soil-water systems can stimulate the decomposition of soil OC (SOC) via priming effects in temperate forests, shrublands, grasslands, and agro-ecosystems. However, priming effects are still not well understood in the field setting for temperate ecosystems and virtually nothing is known about priming effects (e.g., existence, frequency, and magnitude) in boreal ecosystems. In this study, a coupled dissolved OC (DOC) transport and microbial biomass dynamics model was developed to simultaneously simulate co-occurring hydrological, physical, and biological processes and their interactions in soil pore-water systems. The developed model was then used to examine the importance of priming effects in two black spruce forest soils, with and without underlying permafrost. Our simulations showed that priming effects were strongly controlled by the frequency and intensity of DOC input, with greater priming effects associated with greater DOC inputs. Sensitivity analyses indicated that priming effects were most sensitive to variations in the quality of SOC, followed by variations in microbial biomass dynamics (i.e., microbial death and maintenance respiration), highlighting the urgent need to better discern these key parameters in future experiments and to consider these dynamics in existing ecosystem models. Water movement carries DOC to deep soil layers that have high SOC stocks in boreal soils. Thus, greater priming effects were predicted for the site with favorable water movement than for the site with limited water flow, suggesting that priming effects might be accelerated for sites where permafrost degradation leads to the formation of dry thermokarst.     

Induction of the unfolded protein response in familial amyotrophic lateral sclerosis and association of protein-disulfide isomerase with superoxide dismutase 1

Mutations in Cu/Zn superoxide dismutase (SOD1) are linked to motor neuron death in familial amyotrophic lateral sclerosis (ALS) by an unclear mechanism, although misfolded SOD1 aggregates are commonly associated with disease. Proteomic analysis of the transgenic SOD1(G93A) ALS rat model revealed significant up-regulation of endoplasmic reticulum (ER)-resident protein-disulfide isomerase (PDI) family members in lumbar spinal cords. Expression of SOD1 mutants (mSOD1) led to an up-regulation of PDI in motor neuron-like NSC-34 cells but not other cell lines. Inhibition of PDI using bacitracin increased aggregate production, even in wild type SOD1 transfectants that do not readily form inclusions, suggesting PDI may protect SOD1 from aggregation. Moreover, PDI co-localized with intracellular aggregates of mSOD1 and bound to both wild type and mSOD1. SOD1 was also found in the microsomal fraction of cells despite being a predominantly cytosolic enzyme, confirming ER-Golgi-dependent secretion. In SOD1(G93A) mice, a significant up-regulation of unfolded protein response entities was also observed during disease, including caspase-12, -9, and -3 cleavage. Our findings therefore implicate unfolded protein response and ER stress-induced apoptosis in the patho-physiology of familial ALS. The possibility that PDI may be a therapeutic target to prevent SOD1 aggregation is also raised by this study.     

Sexually selected skin colour is heritable and related to fecundity in a non-human primate

Sexual selection promotes the prevalence of heritable traits that increase an individual''s reproductive rate. Despite theoretically strong directional selection, sexually selected traits can show inter-individual variation. Here, we investigate whether red skin ornamentation, a rare example of a male mammalian trait involved in mate attraction, influences fecundity and is heritable in rhesus macaques (Macaca mulatta), and explore the mechanisms that are involved in maintaining trait variation. Interestingly, the trait is expressed by and is attractive to both sexes. We collected facial images of 266 free-ranging individuals and modelled skin redness and darkness to rhesus macaque vision. We used 20 years of genetic parentage data to calculate selection gradients on the trait and perform heritability analyses. Results show that males who were both darkly coloured and high-ranking enjoyed higher fecundity. Female skin redness was positively linked to fecundity, although it remains unclear whether this influences male selectiveness. Heritability explained 10–15% of the variation in redness and darkness, and up to 30% for skin darkness when sexes are considered separately, suggesting sex-influenced inheritance. Our results suggest that inter-individual variation is maintained through condition-dependence, with an added effect of balancing selection on male skin darkness, providing rare evidence for a mammalian trait selected through inter-sexual selection.     

Actin is not an essential component in the mechanism of calcium-triggered vesicle fusion

Actin has been suggested as an essential component in the membrane fusion stage of exocytosis. In some model systems disruption of the actin filament network associated with exocytotic membranes results in a decrease in secretion. Here we analyze the fast Ca2+-triggered membrane fusion steps of regulated exocytosis using a stage-specific preparation of native secretory vesicles (SV) to directly test whether actin plays an essential role in this mechanism. Although present on secretory vesicles, selective pharmacological inhibition of actin did not affect the Ca2+-sensitivity, extent, or kinetics of membrane fusion, nor did the addition of exogenous actin or an anti-actin antibody. There was also no discernable affect on inter-vesicle contact (docking). Overall, the results do not support a direct role for actin in the fast, Ca2+-triggered steps of regulated membrane fusion. It would appear that actin acts elsewhere within the exocytotic cycle.     

Reversible inhibition of mitochondrial complex I activity following chronic dopaminergic glutathione depletion in vitro: implications for Parkinson's disease

The pathogenesis underlying the selective degeneration of nigral dopaminergic neurons in Parkinson's disease is not fully understood but several lines of evidence implicate the role of oxidative stress and mitochondrial dysfunction. Depletion in levels of the thiol reducing agent glutathione (GSH + GSSG) is the earliest reported biochemical event to occur in the Parkinsonian substantia nigra prior to selective loss of complex I (CI) activity associated with the disease believed to contribute to subsequent dopaminergic cell death. Recent studies from our laboratory have demonstrated that acute reduction in both cellular and mitochondrial glutathione levels results in increased oxidative stress and a decrease in mitochondrial function linked to a selective decrease in CI activity through an NO-mediated mechanism (Jha, N.; Jurma, O.; Lalli, G.; Liu, Y.; Pettus, E. H.; Greenamyre, J. T.; Liu, R. M.; Forman, H. J.; Andersen, J. K. Glutathione depletion in PC12 results in selective inhibition of mitochondrial complex I activity. Implications for Parkinson's disease J. Biol. Chem. 275: 26096-26101; 2000. Hsu, M.; Srinivas, B.; Kumar, J.; Subramanian, R.; Andersen, J. Glutathione depletion resulting in selective mitochondrial complex I inhibition in dopaminergic cells is via an NO-mediated pathway not involving peroxynitrite: implications for Parkinson's disease J. Neurochem. 92: 1091-1103.2005.). However, the effect of prolonged glutathione depletion on dopaminergic cells is not known. In this present study, using low concentrations of buthionine-S-sulfoximine, a chemical inhibitor of the de novo glutathione synthesizing enzyme glutamate cysteine ligase, we developed a chronic model in which glutathione depletion in dopaminergic N27 cells for a 7-day period was found to lead to inhibition of CI activity via a peroxynitrite-mediated event which is reversible by the thiol reducing agent, dithiothreitol, and coincides with increased S-nitrosation of mitochondrial proteins.