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 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:Analysis of microbial community composition in arctic tundra and boreal forest soils using serial analysis of ribosomal sequence tags (SARST). Keywords: other
Project description:microarray experiment to test the gene expression in long term lines of mutator and non-mutator yeast. Here we use an experimental evolution approach to investigate the conditions required for evolution of a reduction in mutation rate and the mechanisms by which populations tolerate the accumulation of deleterious mutations. We find that after ~6700 generations four out of eight experimental mutator lines had evolved a decreased mutation rate.
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: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:Following the dispersal out of Africa, where hominins evolved in warm environments for millions of years, our species has colonised different climate zones of the world, including high latitudes and cold environments. The extent to which human habitation in (sub-)Arctic regions has been enabled by cultural buffering, short-term acclimatization and genetic adaptations is not clearly understood. Present day indigenous populations of Siberia show a number of phenotypic features, such as increased basal metabolic rate, low serum lipid levels, increased blood pressure, short stature and broad skulls that have been attributed to adaptation to the extreme cold climate. We have genotyped 200 individuals from ten indigenous Siberian populations for 730,525 SNPs across the genome to identify genes and non-coding regions that have undergone unusually rapid allele frequency and long-range haplotype homozygosity change in the recent past. At least three distinct population clusters could be identified among the Siberians, each of which showed a number of unique signals of selection. We present a list of cold adaption candidate genes that showed significant signals of positive selection with our strongest signals associated with genes involved in energy regulation and metabolism (CPT1A, LRP5, THADA) and vascular smooth muscle contraction (PRKG1). By employing a new method that paints phased chromosome chunks by their ancestry we distinguish local Siberian-specific long-range haplotype signals from those introduced by admixture. 200 blood samples from 200 Siberian individuals that come from ten different indigenous populations were genotypes for 730,525 SNPs across the genome. Eighteen Vietnamese samples were also genotyped and used as reference samples.
Project description:Differential gene expression in a wide range of tissues including brown adipose tissue (BAT), liver, heart, hypothalamus, and skeletal muscle in hibernating arctic ground squirrels during multiple stages in torpor-arousal cycles compared to non-hibernating (post-reproductive) animals with illumina beadarray technology. Keywords: Multiple stage comparison
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:Arctic charr is an especially attractive aquaculture species given that it features the desirable tissue traits of other salmonids, but can be bred and grown at inland freshwater tank farms year round. It is therefore of interest to develop upper temperature tolerant (UTT) strains of Arctic charr to increase the robustness of the species in the face of climate change, as well as to enable production in more southern regions. We conducted an acute temperature trial to identify temperature tolerant and intolerant Arctic charr individuals. Specifically, approximately 200 fish were transferred to an experimental tank (diameter: 1.86 m, depth 50 cm) and left to acclimate for 48 h at ambient temperature. After acclimation, 10 fish were removed to act as a control group, then water that had been diverted through a heat exchanger was added to the flow-through system to increase the water temperature in the tank by 6°C/h until it reached 22°C, then 0.5°C every 30 min until the water reached 25°C, the observed lethal temperature for these fish. When the water temperature reached 25°C, the temperature was held constant and the fish were closely monitored for signs of stress. The first and last 10 individuals to show loss of balance were quickly removed from the tank for sampling, thus representing the 5% least and most temperature tolerant fish, respectively. A reference design microarray study was then performed with the cGRASP 32K microarray using six samples from each group (Intolerant, Tolerant, Control) to identify genes differentially expressed between groups. The results of this study will feed into an ongoing Arctic charr marker-assisted selection based broodstock development program, and may contribute to population-based conservation initiatives for salmonids in general.