Reliability analysis of reconstructing phylogenies under long branch attraction conditions

Master's Project (M.S.) University of Alaska Fairbanks, 2018.In this simulation study we examined the reliability of three phylogenetic reconstruction techniques in a long branch attraction (LBA) situation: Maximum Parsimony (M P), Neighbor Joining (NJ), and Maximum Likelihood. Data were simulated under five DNA substitution models-JC, K2P, F81, HKY, and G T R-from four different taxa. Two branch length parameters of four taxon trees ranging from 0.05 to 0.75 with an increment of 0.02 were used to simulate DNA data under each model. For each model we simulated DNA sequences with 100, 250, 500 and 1000 sites with 100 replicates. When we have enough data the maximum likelihood technique is the most reliable of the three methods examined in this study for reconstructing phylogenies under LBA conditions. We also find that MP is the most sensitive to LBA conditions and that Neighbor Joining performs well under LBA conditions compared to MP

Role of TGFbRII in myeloid cell mediated regenerative processes and fibroplasia

Tissue repair and fibrosis are controlled by the interaction of different cell lineages, their soluble factors and matrix signals. Recently, macrophages have been found to be crucial for proper tissue repair. In particular, the role of Transforming growth factor-β1 (TGF-β1) has been extensively studied during tissue repair and fibrosis. Fibrosis is characterized by excessive production and deposition of extracellular matrix, as well as immune cell infiltration. Macrophages are one of the main sources of TGF-β1. So far, studies on the mechanisms of tissue repair and fibrosis have mainly focused on macrophages or TGF-β1 individually. However, the specific function of TGF-β1 on macrophages in tissue repair and fibrosis still needs to be elucidated. To understand the macrophage specific role of TGFβ1-TGFβRII signaling in tissue repair and fibrosis, we generated a mouse model, which lacks TGFβRII in myeloid cells (TGFβRIIfl/fl/LysMCre). We observed that during mechanical tissue injury TGFβRII signaling in macrophages contributes to wound contraction, possibly by cross—talk between macrophages and fibroblasts. The attenuated wound contraction was accompanied by impaired myofibroblast differentiation and collagen deposition. However, the loss of TGFβRII signaling in macrophages did not lead to reduced expression of TGF- β1, which we proposed as one of the primary mechanisms in wound tissue underlying reduced myofibroblast formation observed in TGFβRIIfl/fl/LysMCre mice. Generation of cutaneous fibrosis by bleomycin injection for two and four weeks resulted in reduced fibrosis in TGFβRIIfl/fl/LysMCre mice, compared to control mice. The mechanisms leading to this phenotype were associated with reduced infiltration of immune cells, reduced deposition of collagen and diminished production of inflammatory mediators such as IL-1β, TNF-α and osteopontin-1 at the early stage of fibrosis formation. At the later stage, the expression of inflammatory mediators in TGFβRIIfl/fl/LysMCre mice was not altered compared to control mice, possibly due to compensatory mechanisms. Our data leads to the hypothesis that the reduced fibrosis is caused by the reduced expression of inflammatory mediators and accumulation of immune cells at the early stage of fibrosis in TGFβRIIfl/fl/LysMCre mice. Our results provide new insights into the crucial role of macrophage specific TGFβRII signaling in tissue repair and fibrosis