Removal of AMPA receptors (AMPARs) from synapses is preceded by transient endocytosis of extrasynaptic AMPARs

AMPA receptors (AMPARs) are dynamically regulated at synapses, but the time course and location of their exocytosis and endocytosis are not known. Therefore, we have used ecliptic pHluorin-tagged glutamate receptor 2 to visualize changes in AMPAR surface expression in real time. We show that synaptic and extrasynaptic AMPARs respond very differently to NMDA receptor activation; there is a rapid internalization of extrasynaptic AMPARs that precedes the delayed removal of synaptic AMPARs

PATTERNS IN ENVIRONMENTAL DRIVERS OF WETLAND FUNCTIONING AND SPECIES COMPOSITION IN A COMPLEX PEATLAND

The boreal peatlands that cover much of western Canada are immense reservoirs of organic carbon and nitrogen, serving as sinks for atmospheric carbon, as well as providing habitat for flora and fauna, and nutrient cycling. These ecosystems are generally believed to be nitrogen limited. Due to regional increases in industrial activities associated in the Athabasca Oil Sands Region (AOSR), atmospheric deposition of nitrogen is projected to increase, with unknown effects on peatland functioning. The results of this study provide baseline data for a nitrogen fertilization experiment with an accurate site description of the entire peatland complex to provide reference for the experiment. This study also examines patterns in production and nitrogen usage along a wet to dry gradient. My main question was if species assemblages could be sorted into communities and how these were related to environmental gradients. In chapters three and four I asked how production and nitrogen usage and storage varied along a moisture gradient. In chapter two, four communities were identified as being independent with clear indicator species. These communities had differences in abiotic factors formed clear gradients across the peatland, influencing the distribution of species arrangements in the peatland complex. Sphagnum angustifolium thrived in all four communities and across the entire range of gradients. This species is a foundation of species of bogs and poor fens and was studied in more detail in chapters 3 and 4. In chapter three, I found that primary production of S. angustifolium increased from dry to wet along the moisture gradient. Cranked wires used to measure linear growth became less reliable in wetter habitats, missing over 50 % of growth measure by innate time markers. Capitula increased in biomass throughout the course of the growing season, suggesting that after vertical elongation, S. angustifolium begins to accumulate branches and leaves in the capitula to close the growing season. Chapter four, evaluating nitrogen requirements found that while primary production of S. angustifolium increased from dry to wet, tissue quality of the growth decreased along this gradient. Despite the lower tissue quality, wet habitats had higher nitrogen requirements to support growth rates. Inputs of atmospheric deposition fulfilled \u3c5% of annual N requirements and nitrogen saturated capitula in the beginning of the season was found to be an important source of nitrogen for growth, as capitula nitrogen storage declined over the season. Of the total nitrogen assimilated into annual growth, the percent lost a year later was similar across the moisture gradient; more nitrogen is stored in the wet habitats, strictly due to higher amounts initially assimilated. The results of this study suggest that in drier peatland habitats, there is an insufficient supply of water to deliver nitrogen and to support continuous growth during the growing season. Consequently, in wetter habitats, production is limited by nitrogen while in drier habitats it is limited by climate

Experimental nitrogen addition alters structure and function of a boreal bog: critical load and thresholds revealed

Bogs and fens cover 6% and 21%, respectively, of the 140,329 km2 Oil Sands Administrative Area in northern Alberta. Development of the oil sands has led to increasing atmospheric N deposition, with values as high as 17 kg N.ha-1yr-1; regional background deposition is N.ha-1yr-1. Bogs, being ombrotrophic, may be especially susceptible to increasing N deposition. To examine responses to N deposition, over five years, we experimentally applied N (as NH4NO3) to a bog near Mariana Lake, Alberta, unaffected by oil sands activities, at rates of 0, 5, 10, 15, 20, and 25 kg N.ha-1yr-1, plus controls (no water or N addition). Increasing N addition: (1) stimulated N2 fixation at deposition .ha-1yr-1, and progressively inhibited N2 fixation as N deposition increased above this level; (2) had no effect on Sphagnum fuscum net primary production (NPP) in years 1, 2, and 4, but inhibited S. fuscum NPP in years 3 and 5; (3) stimulated dominant shrub and Picea mariana NPP; (4) led to increased root biomass and production; (5) changed Sphagnum species relative abundance (decrease in S. fuscum, increase in S. magellanicum, no effect on S. angustifolium); (6) led to increasing abundance of Rhododendron groenlandicum and Andromeda polifolia, and to vascular plants in general; (7) led to increasing shrub leaf N concentrations in Andromeda polifolia, Chamaedaphne calyculata, Vaccinium oxycoccos, V. vitis-idaea, and Picea mariana; (8) stimulated cellulose decomposition, with no effect on S. fuscum peat or mixed vascular plant litter decomposition; (9) had no effect on net N mineralization rates or on porewater NH4+-N, NO3--N, or DON concentrations; and (10) had minimal effects on peat microbial community composition. Increasing experimental N addition led to a switch from new N being taken up primarily by Sphagnum to being taken up primarily by shrubs. As shrub growth and cover increase, Sphagnum abundance and NPP decrease. Because inhibition of N2 fixation by increasing N deposition plays a key role in bog structural and functional responses, we recommend a N deposition critical load of 3 kg N.ha-1yr-1 for northern Alberta bogs

Factor analyses differentiate clinical phenotypes of idiopathic and interferon-alpha-induced depression

The discovery that prolonged administration of interferon-alpha (a pro-inflammatory cytokine) readily precipitates depressive symptoms has played a key role in development of the inflammation theory of major depressive disorder (MDD). However, it remains unclear whether the clinical phenotype of patients with inflammation-associated depression significantly overlaps with, or can be distinguished from that of patients with ‘idiopathic’ depression. Here we explored the Hamilton depression scale factor structure of 172 patients undergoing interferon-alpha treatment for hepatitis-C at the point of transition to a depressive episode of DSM IV defined major depression severity. The resulting factor structure was first compared with a model derived from 6 previous studies of ‘idiopathic’ MDD (Cole et al., 2004). This confirmatory factor analysis revealed that the factor structure of HAMD scores in our interferon-alpha treated cohort did not plausibly fit that previously described for ‘idiopathic’ MDD. Instead, subsequent exploratory factor analysis revealed a distinct four factor model with a novel primary factor grouping cognitive symptoms of depression and anxiety (HAMD items 1, 2, 9, 10, 11, 15). The second sleep disorder factor (items 4, 5, 6) replicated previous findings in ‘idiopathic’ depression. A third and unique factor grouped somatic symptoms and function (items 7, 12, 13, 14 and item 1). The final factor (also common in idiopathic depression studies), grouped gastrointestinal symptoms and weight loss (items 12 and 16). Severe depression items (3, 8, and 17) were excluded from analysis due to very low variance. At transition, interferon-alpha induced major depressive episodes therefore appears to have more associated anxiety features that covary with depressed mood than classical or ‘idiopathic’ MDD and a low likelihood of severe features such as suicidal ideation. Identification of this clinical phenotype may help identify patients with an inflammatory depression etiology and support the development of more effective and personalized therapies

Biomarker Validation of Dietary Intervention in Two Multiethnic Populations

Introduction: Intervention studies have been designed to change dietary and lifestyle factors associated with chronic diseases, but self-reported behavior change may incorporate intervention-related bias. This study examines plasma nutrient concentration and correlations with self-reports in the Healthy Directions intervention study. The Healthy Directions intervention studies were designed to increase multivitamin use, fruit and vegetable consumption, and physical activity in working-class, multiethnic populations. Methods: Participants in both studies completed interviewer-administered questionnaires that collected information on sociodemographic and health behavior characteristics. Postintervention blood samples were collected from 209 participants and pooled in pairs within study and within intervention group. Results: We found significantly higher plasma concentrations of retinol (P = .01) and α-carotene (P = .03) in the intervention than in the usual care group. Self-reported multivitamin users had significantly higher concentrations of retinol (P < .001), β-carotene (P = .02), and α-tocopherol (P < .001). Those who reported four or more fruit and vegetable servings per day had higher lutein and zeaxanthin (P = .05) and β-cryptoxanthin (P = .05) concentrations than those consuming fewer. Plasma nutrient concentrations were associated with reported multivitamin use and fruit and vegetable intake, but the correlations were generally higher in the usual care group. Conclusion: We found significant postintervention differences in plasma carotenoid and tocopherol concentrations by treatment group, multivitamin use, and fruit and vegetable intake. However, because we only obtained postintervention blood samples, we were unable to assess preintervention-to-postintervention changes in plasma nutrients. Self-reported intakes were significantly correlated with plasma nutrient concentrations, but the strength of the correlations differed by group, suggesting some intervention-related bias in the questionnaire responses

Experimental nitrogen addition alters structure and function of a boreal poor fen: Implications for critical loads

Bogs and fens cover 6 and 21%, respectively, of the 140,329 km2 Oil Sands Administrative Area in northern Alberta. Regional background atmospheric N deposition is low (b2 kg N ha−1 yr−1 ), but oil sands development has led to increasing N deposition (as high as 17 kg N ha−1 yr−1 ). To examine responses to N deposition, over five years, we experimentally applied N (as NH4NO3) to a poor fen near Mariana Lake, Alberta, unaffected by oil sands activities, at rates of 0, 5, 10, 15, 20, and 25 kg N ha−1 yr−1 , plus controls (no water or N addition). At Mariana Lake Poor Fen (MLPF), increasing N addition: 1) progressively inhibited N2-fixation; 2) had no effect on net primary production (NPP) of Sphagnum fuscum or S. angustifolium, while stimulating S. magellanicum NPP; 3) led to decreased abundance of S. fuscum and increased abundance of S. angustifolium, S. magellanicum, Andromeda polifolia, Vaccinium oxycoccos, and of vascular plants in general; 4) led to an increase in stem N concentrations in S. angustifolium and S. magellanicum, and an increase in leaf N concentrations in Chamaedaphne calyculata, Andromeda polifolia, and Vaccinium oxycoccos; 5) stimulated root biomass and production;6) stimulated decomposition of cellulose, but not of Sphagnum or vascular plant litter; and 7) had no or minimal effects on net N mineralization in surface peat, NH4 +-N, NO3 −-N or DON concentrations in surface porewater, or peat microbial composition. Increasing N addition led to a switch from new N inputs being taken up primarily by Sphagnum to being taken up primarily by shrubs. MLPF responses to increasing N addition did not exhibit threshold triggers, but rather began as soon as N additions increased. Considering all responses to N addition, we recommend a critical load for poor fens in Alberta of 3 kg N ha−1 yr−1