Paleolimnology of Two Shallow Lakes in Central Alberta,Canada

An interpretation of postglacial change in water quality and productivity has been made for two shallow lakes in Central Alberta, Canada, namely Hastings Lake (longitude 113° 00′ W; latitude 53° 30′ N) and Lac Ste. Anne (longitude 114° 21′ W; latitude 53° 41′ N). Erosion rates around Lac Ste. Anne have remained constant. Similarly productivity has changed little although macrophytes contributed more to total production during the early stages. Hastings Lake has responded more sensitively to changes in the balance of precipitation and evaporation. From 5500 to 4000 year B. P. it was shallower than at present. Productivity during this early phase was less but macrophytes and allochthonous organic matter (i. e., leaf litter) probably contributed a greater proportion of the organic influx. After water levels rose productivity increased remaining steady until 2500 year B. P. when a slight decline occurred. Throughout the high water period oxygen depletion has not been serious. Any period of reducing conditions has been brief. Productivity has never been nutrient-limited. Elevation of the lake surface increased potential volume for production and reduced turbulent resuspension of bottom sediments permitting greater light penetration, and enhanced algal production. Difference between the sedimentary record of these two lakes, as well as the two basins of Hastings Lake, demonstrates the individualistic responses of basins and lakes to climatic events.     

Nonlinear response of nitric oxide fluxes to fertilizer inputs and the impacts of agricultural intensification on tropospheric ozone pollution in Kenya

Crop yields in sub‐Saharan Africa remain stagnant at 1 ton ha^?1, and 260 million people lack access to adequate food resources. Order‐of‐magnitude increases in fertilizer use are seen as a critical step in attaining food security. This increase represents an unprecedented input of nitrogen (N) to African ecosystems and will likely be accompanied by increased soil emissions of nitric oxide (NO). NO is a precursor to tropospheric ozone, an air pollutant and greenhouse gas. Emissions of NO from soils occur primarily during denitrification and nitrification, and N input rates are a key determinant of emission rates. We established experimental maize plots in western Kenya to allow us to quantify the response function relating NO flux to N input rate during the main 2011 and 2012 growing seasons. NO emissions followed a sigmoid response to fertilizer inputs and have emission factors under 1% for the roughly two‐month measurement period in each year, although linear and step relationships could not be excluded in 2011. At fertilization rates above 100 kg N ha^?1, NO emissions increased without a concomitant increase in yields. We used the geos‐chem chemical transport model to evaluate local impacts of increased NO emissions on tropospheric ozone concentrations. Mean 4‐hour afternoon tropospheric ozone concentrations in Western Kenya increased by up to roughly 2.63 ppbv under fertilization rates of 150 kg N ha^?1 or higher. Using AOT40, a metric for assessing crop damage from ozone, we find that the increased ozone concentrations result in an increase in AOT40 exposure of approximately 110 ppbh for inputs of 150 kg N ha^?1 during the March–April–May crop growing season, compared with unfertilized simulations, with negligible impacts on crop productivity. Our results suggest that it may be possible to manage Kenyan agricultural systems for high yields while avoiding substantial impacts on air quality.     

A New Target for Amyloid Beta Toxicity Validated by Standard and High-Throughput Electrophysiology

Background

Soluble oligomers of amyloid beta (Aβ) are considered to be one of the major contributing factors to the development of Alzheimer''s disease. Most therapeutic development studies have focused on toxicity directly at the synapse.

Methodology/Principal Findings

Patch clamp studies detailed here have demonstrated that soluble Aβ can also cause functional toxicity, namely it inhibits spontaneous firing of hippocampal neurons without significant cell death at low concentrations. This toxicity will eventually lead to the loss of the synapse as well, but may precede this loss by a considerable amount of time. In a key technological advance we have reproduced these results utilizing a fast and simple method based on extracellular electrophysiological recording of the temporal electrical activity of cultured hippocampal neurons using multielectrode arrays (MEAs) at low concentrations of Aβ (1–42). We have also shown that this functional deficit can be reversed through use of curcumin, an inhibitor of Aβ oligomerization, using both analysis methods.

Conclusions/Significance

The MEA recording method utilized here is non-invasive, thus long term chronic measurements are possible and it does not require precise positioning of electrodes, thus it is ideal for functional screens. Even more significantly, we believe we have now identified a new target for drug development for AD based on functional toxicity of hippocampal neurons that could treat neurodegenerative diseases prior to the development of mild cognitive impairment.     

Parallel liquid synthesis of N,N'-Disubstituted 3-amino azepin-2-ones as potent and specific farnesyl transferase inhibitors

A rapid structure-activity study was performed by parallel liquid synthesis on N,N'-disubstitution of 3-amino azepin-2-one to afford potent and specific farnesyl transferase inhibitors with low nM enzymatic and cellular activities. The activities of the selected compounds were validated in vivo, and compounds 41a and 44a presented significant antitumour activity.     

Cutting edge: class I presentation of host peptides following HIV infection

Class I MHC molecules bind intracellular peptides for presentation to cytotoxic T lymphocytes. Identification of peptides presented by class I molecules during infection is therefore a priority for detecting and targeting intracellular pathogens. To understand which host-encoded peptides distinguish HIV-infected cells, we have developed a mass spectrometric approach to characterize HLA-B*0702 peptides unique to or up-regulated on infected T cells. In this study, we identify 15 host proteins that are differentially presented on infected human T cells. Peptides with increased expression on HIV-infected cells were derived from multiple categories of cellular proteins including RNA binding proteins and cell cycle regulatory proteins. Therefore, comprehensive analysis of the B*0702 peptide repertoire demonstrates that marked differences in host protein presentation occur after HIV infection.     

Mycobacterium tuberculosis induces differential cytokine production from dendritic cells and macrophages with divergent effects on naive T cell polarization

Th1-mediated cellular responses are important for protection in tuberculosis. However, the mechanisms and APC types responsible for initiating Th1 responses are not well understood. These studies show that macrophages and dendritic cells, albeit both being APC, respond differently following Mycobacterium tuberculosis infection and thereby have different consequences for the development of naive T cells. We report that M. tuberculosis-infected dendritic cells bias the polarization of OVA peptide-specific naive transgenic T cells to the Th1 phenotype, and, in contrast, in the presence of infected macrophages naive T cells do not develop a Th1 phenotype. Comparison of the cytokine profile expressed by the infected dendritic cells and macrophages revealed several differences, the most striking being that infected macrophages did not express the Th1-promoting cytokine IL-12. These studies also show that IL-10 is responsible for the failure of IL-12 production by M. tuberculosis-infected macrophages, and that the effects of IL-10 can be overcome by IFN-gamma priming. We speculate that the observed difference in response of the two APC types to M. tuberculosis infection may be a reflection of their respective roles in immune initiation and granuloma regulation.     

Chromate reduction in Shewanella oneidensis MR-1 is an inducible process associated with anaerobic growth

Cr(VI) reduction was observed during tests with Shewanella oneidensis MR-1 (previously named S. putrefaciens MR-1) while being grown with nitrate or fumarate as electron acceptor and lactate as electron donor. From the onset of anoxic growth on fumarate, we measured a gradual and progressive increase in the specific Cr(VI) reduction rate with incubation time until a maximum was reached at late exponential/early stationary phase. Under denitrifying conditions, the specific Cr(VI) reduction rate was inhibited by nitrite, which is produced during nitrate reduction. However, once nitrite was consumed, the specific reduction rate increased until a maximum was reached, again during the late exponential/early stationary phase. Thus, under both fumarate- and nitrate-reducing conditions, an increase in the specific Cr(VI) reduction rate was observed as the microorganisms transition from oxic to anoxic growth conditions, presumably as a result of induction of enzyme systems capable of reducing Cr(VI). Although Cr(VI) reduction has been studied in MR-1 and in other facultative bacteria under both oxic and anoxic conditions, a transition in specific reduction rates based on physiological conditions during growth is a novel finding. Such physiological responses provide information required for optimizing the operation of in situ systems for remediating groundwater contaminated with heavy metals and radionuclides, especially those that are characterized by temporal variations in oxygen content. Moreover, such information may point the way to a better understanding of the cellular processes used by soil bacteria to accomplish Cr(VI) reduction.     

YC-1, a benzyl indazole derivative, stimulates vascular cGMP and inhibits neointima formation

The pathobiologic process of arterial stenosis following balloon angioplasty continues to be an enigmatic problem in clinical settings. This research project investigates the ability of YC-1, a benzyl indazole derivative that sensitizes sGC/cGMP, to stimulate endogenous cGMP and attenuate balloon injury-induced neointima (NI) formation in the rat carotid artery. Northern and Western blot analyses revealed enhanced acute expression of iNOS and inducible heme oxygenase (HO-1) mRNA and protein in the injured artery. The contralateral uninjured artery also demonstrated acute HO-1 mRNA and protein induction without detectable iNOS expression. Perivascular application of YC-1 immediately following injury significantly stimulated acute vessel wall cGMP compared to untreated controls. YC-1 treated sections demonstrated significant reduction in NI area (-74%), NI area/medial wall area (-72%), and NI thickness (-76%) 2 weeks post-injury. These results directly implicate YC-1 as a potent new therapeutic agent capable of reducing post-angioplasty stenosis through endogenous CO- and/or NO-mediated, cGMP-dependent processes.