Project description:C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, is primarily expressed on cells of the myeloid lineage, and to a lesser extent on endothelial cells and neurons in brain. Previous work demonstrated C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in Alzheimer Disease (AD) mouse models. In the Arctic AD mouse model, genetic deletion of C5aR1 prevented behavior deficits at 10 months. However, the molecular mechanisms of this protection has not been definitively demonstrated. To understand the role of microglial C5aR1 in the Arctic AD mouse model, we have taken advantage of the CX3CR1GFP and CCR2RFP reporter mice to distinguish microglia as GFP-positive and infiltrating monocytes as GFP and RFP positive, for subsequent transcriptome analysis on specifically sorted myeloid populations from wild type and AD mouse models. Immunohistochemical analysis of mice aged to 2, 5, 7 and 10 months showed no change in amyloid beta (Ab) deposition in the Arctic C5aR1 knockout (KO) mice relative to that seen in the Arctic mice. Of importance, no CCR2+ monocytes/macrophages were found near the plaques in the Arctic brain with or without C5aR1. RNA-seq analysis on microglia from these mice identified inflammation related genes as differentially expressed, with increased expression in the Arctic mice relative to wildtype and decreased expression in the Arctic/C5aR1KO relative to Arctic. In addition, phagosomal-lysosomal proteins and protein degradation pathways that were increased in the Arctic mice were further increased in the Arctic/C5aR1KO mice. These data are consistent with a microglial polarization state with restricted induction of inflammatory genes and enhancement of clearance pathways.
Project description:The objective of this study was to identify the different functional genes involved in key biogeochemical cycles in thehigh Arctic regions. Understanding the microbial diversity in the Arctic region is an important step to determine the effects of climate change on these areas.
Project description:To carry out population genetics analyses of the Arctic gregion we carried out Illumina Bead-Array-based enotyping on 18 samples from Greenland.
Project description:The objective of this study was to identify the different functional genes involved in key biogeochemical cycles in the sub- Arctic regions. Understanding the microbial diversity in the Arctic region is an important step to determine the effects of climate change on these areas.
Project description:The objective of this study was to identify the different functional genes involved in key biogeochemical cycles in the low Arctic regions. Understanding the microbial diversity in the Arctic region is an important step to determine the effects of climate change on these areas.
Project description:The effects of ocean acidification (OA) on nitrous oxide (N2O) production and on the community composition of ammonium oxidising archaea (AOA) were examined in the northern and southern sub-polar and polar Atlantic Ocean. Two research cruises were performed during June 2012 between the North Sea and Arctic Greenland and Barent Seas, and in January-February 2013 to the Antarctic Scotia Sea. Seven stations were occupied in all during which shipboard experimental manipulations of the carbonate chemistry were performed through additions of NaHCO3- + HCl in order to examine the impact of short- term (48 hour for N2O and between 96 and 168 hour for AOA) exposure to control and elevated conditions of OA. During each experiment, triplicate incubations were performed at ambient conditions and at 3 lowered levels of pH which varied between 0.06 and 0.4 units according to the total scale and which were targeted at CO2 partial pressures of ~500, 750 and 1000 μatm. The AOA assemblage in both Arctic and Antarctic regions was dominated by two major archetypes that represent the marine AOA clades most often detected in seawater. There were no significant changes in AOA assemblage composition between the beginning and end of the incubation experiments. N2O production was sensitive to decreasing pHT at all stations and decreased by between 2.4 and 44% with reduced pHT values of between 0.06 and 0.4. The reduction in N2O yield from nitrification was directly related to a decrease of between 28 and 67% in available NH3 as a result of the pH driven shift in the NH3:NH4+ equilibrium. The maximum reduction in N2O production at conditions projected for the end of the 21st century was estimated to be 0.82 Tg N y-1.