Landscape Patterns of Permafrost Disturbance and Degradation in the Canadian High Arctic

Intensification of permafrost disturbances such as active layer detachments (ALDs) and retrogressive thaw slumps (RTS) have been observed across the circumpolar Arctic. These features are indicators of unstable conditions stemming from recent climate warming and permafrost degradation. In order to understand the processes interacting to give rise to these features, a multidisciplinary approach is required; i.e., interactions between geomorphology, hydrology, vegetation and ground thermal conditions. The goal of this research is to detect and map permafrost disturbance, predict landscape controls over disturbance and determine approaches for monitoring disturbance, all with the goal of contributing to the mitigation of permafrost hazards. Permafrost disturbance inventories were created by applying semi-automatic change detection techniques to IKONOS satellite imagery collected at the Cape Bounty Arctic Watershed Observatory (CBAWO). These methods provide a means to estimate the spatial distribution of permafrost disturbances for a given area for use as an input in susceptibility modelling. Permafrost disturbance susceptibility models were then developed using generalized additive and generalized linear models (GAM, GLM) fitted to disturbed and undisturbed locations and relevant GIS-derived predictor variables (slope, potential solar radiation, elevation). These models successfully delineated areas across the landscape that were susceptible to disturbances locally and regionally when transferred to an independent validation location. Permafrost disturbance susceptibility models are a first-order assessment of landscape susceptibility and are promising for designing land management strategies for remote permafrost regions. Additionally, geomorphic patterns associated with higher susceptibility provide important knowledge about processes associated with the initiation of disturbances. Permafrost degradation was analyzed at the CBAWO using differential interferometric synthetic aperture radar (DInSAR). Active-layer dynamics were interpreted using inter-seasonal and intra-seasonal displacement measurements and highlight the importance of hydroclimatic factors on active layer change. Collectively, these research approaches contribute to permafrost monitoring and the assessment of landscape-scale vulnerability in order to develop permafrost disturbance mitigation strategies.

Roles of the Immune Cytokine Environment on Clonal Growth of Murine and Human Tet2 Mutant Bone Marrow Progenitors: Implications for Myelodysplastic Syndromes

TET2 is a tumor suppressor gene that has been implicated in the epigenetic regulation of gene expression. Inactivating TET2 mutations are common in MDS. These mutations may contribute to early clonal dominance and myeloid transformation, although the exact mechanisms remain to be elucidated. Common to the environment of MDS are elevations in cytokines, such as TNFα and IFN-γ. It was hypothesized that inflammatory cytokines TNF-α and IFN-γ may promote clonal expansion of TET2 mutant progenitors. Adult (10-14 weeks-old) Tet2 wild type (+/+) and Tet2 mutant (-/-) C57BL/6 mice strains were chosen as a model system. Lineage negative cells (Lin-), enriched for hematopoietic stem and progenitor cells, were isolated from Tet2 +/+ and -/- bone marrow and cultured in the absence or presence of varying concentrations of TNFα or IFN-γ in methylcellulose colony formation assays and long term cell culture assays, over a period of 12 and 30 days respectively, and their colony growth, cell count, immunophenotype and resistance to apoptosis were examined. Where indicated, serial re-plating was performed. Expression of apoptotic regulators was assessed by qRT-PCR. In the triplicate experiments, starting with equal densities of Tet2 +/+ and -/- Lin- cells, Tet2 -/- Lin- cells displayed increased resistance to cytokine-induced growth suppression and superior colony forming ability over +/+ in the serial re-plating assays under stress of increasing TNFα or IFN γ. Tet2 -/- progenitors also displayed a lower apoptotic index compared to +/+ under stress of increasing TNFα, suggesting increased resistance to TNFα induced apoptosis. Transcriptional data showed low expression of Tnfr1, Fas and caspase 8, as well as a high expression of Bcl-2 and Iap1 in Tet2 -/- compared to +/+ under stress of TNFα. Tet2-/- also showed increased basal expression of endogenous TNFα mRNA compared to +/+. In the human colony growth assay, the clonal growth of TET2 mutant CFU-GM progenitors was enhanced at low TNFα concentrations. Conclusion: Mutations that promote resistance to environmental stem cell stressors are a known mechanism of clonal selection in aplastic anaemia and JAK2-mutant MPN and our findings suggest that this mechanism may be critical to clonal selection and dominance in MDS.