Dark matter in dwarf irregular galaxies, DDO 210 and DDO 169

It has been proposed that dwarf irregular galaxies can be separated into two classes based on their formation mechanism; that they are the result of the collapse of a primordial gas cloud or that they are the product of condensation of gas in the tidal tails of interacting galaxies. Simulations of galaxy interactions indicate that one can differentiate between these two scenarios by the dark matter content, with a low dark matter content indicating a fossil tidal dwarf. The purpose of this dissertation was to explore the dark matter distribution of two dwarf irregular galaxies using optical and neutral atomic hydrogen data. For DDO 210, the method of mass-modelling was used to determine its dark matter. About 64% of the galaxy mass was calculated to be in the form of dark matter and hence it is unlikely to be a fossil tidal dwarf. The method of mass-modelling could not be used for DDO 169 as the galaxy shows evidence of being tidally disrupted and hence, has a disturbed velocity field. Instead, the suggestion that dark matter might be responsible for a pressure anomaly in DDO 169 was tested to determine its dark matter content. According to this method, a pressure anomaly does exist but without a concrete value for the scale-height, it is unclear whether the anomaly is due to the presence of dark matter. Hence one cannot say how much dark matter might actually be present in DDO 169. A rotation curve would be required to do this. ^

Cocaine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells by Suppressing microRNA-155

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers.