Browsing by Subject "College of Biological Science"
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Item Astrocytic Ca2+ Levels are Regulated by Estradiol(2017) Loke, Kelvin; Araque, AlfonsoItem Developing a Disulfide Replacement Picture of APOBEC3G(2010-04-21) Biermann, MitchThe human protein APOBEC3G (A3G) interferes with HIV infection by acting as a cytidine deaminase, an enzyme that induces numerous mutations in HIV’s genetic material that ultimately destroy it. But A3G is only successful at this for a time. The HIV protein viral infectivity factor (Vif) destroys A3G. Developing a way to mask A3G from Vif is a major therapeutic goal. Uncovering the three-dimensional structure of A3G is crucial to rational drug design. The catalytic C-terminal domain of A3G has been solved, but the crucial Vif-interacting N-terminal domain remains invisible to medicinal chemists. A major obstacle toward this goal is the N-terminal domain’s poor solubility. Here we explore a novel technique, disulfi de replacement, in which pairs of cysteine residues are incorporated into the protein at hypothetically close positions and checked for disulfi de bonding. We isolated a model peptide containing a disulfi de bond from its reduced form, and we observed an engineered disulfi de from the Ctd of A3G at two residues known to be spatially close. However, the sensitivity of the approach in digested peptide samples must be improved. We would like to acknowledge Yongjian Lu, Takahide Kono, the Chemistry Department Mass Spectrometry Facility, and all the other members of the Matsuo lab for their support.Item From Soil to Squirrel: The Legacy of Lead Pollution & Its Effects on Urban Wildlife Behavior(2024-04-18) Schulz, Rachel K; Devitz, Amy-Charlotte; Snell-Rood, Emilie CUrbanization increasingly threatens wildlife through the introduction of novel threats and pollution. Animals can use behavior to adapt to urban environments and urban pollutants drive changes in behavior, leading to populations of urban wildlife with some behaviors that are distinct from rural populations. Lead (Pb) pollution is ubiquitous in urban areas, but there can be significant local variation in soil lead levels. In this study, I examined the relationship between soil lead, hair lead, docility, and aggressive and social behavior in eastern gray squirrels (Sciurus carolinensis) and eastern chipmunks (Tamias striatus) in Minneapolis and Saint Paul, Minnesota. Docility was measured through a struggle test and aggressive and social responses were measured in a mirror image stimulation trial. Soil lead and hair lead were significantly positively correlated in gray squirrels and chipmunks, and there was no difference in hair lead based on species or sex. Chipmunks had significantly longer struggle times than gray squirrels, but struggle time did not vary based on hair lead or sex. Only six of 235 animals displayed aggression in the mirror image stimulation trial, and frequency of contacting the mirror in a nonaggressive way was not correlated with hair lead, species, or sex. These results provide correlational evidence of lead transfer from soils to gray squirrels and chipmunks, though the magnitude of lead accumulation does not seem to depend on the distinct life histories of these two species. At the levels currently present in these urban environments, lead does not affect aggressive or social behavior in gray squirrels or chipmunks. Future studies should examine aggression through direct observation rather than a mirror image stimulation trial to better quantify aggression in these species that have low territorial aggression.Item Mechanisms of Androgen-Mediated Repression of the Maspin Tumor Suppressor Gene in Prostate Cancer(2010-04-21) Bader, DavidProstate Cancer (PCa) is the second leading cause of cancer death in American men; one in six will be diagnosed with the disease during his lifetime. The androgen receptor (AR) is a transcription factor necessary for normal prostate cell growth as well as for growth of PCa. When AR is activated by androgens, it translocates to the nucleus and exerts transcriptional activation and repression of target genes. Significant efforts have focused on characterizing genes that are activated by AR such as prostate specific antigen (PSA), a marker for PCa screening. Genes that are transcriptionally repressed by AR are also likely to play a role in the progression of prostate cancer, yet the mechanisms behind their repression have received less attention. One such gene is maspin, a tumor suppressor gene that is repressed by androgens. Maspin expression is associated with increased cellular adhesion, increased sensitivity to cellular apoptosis, and decreased angiogenesis in the tumor microenvironment. In this study, we demonstrated that (1) Maspin is repressed following androgen treatment, (2) the repression is mediated in a direct manner, and (3) Androgen antagonists such as bicalutamide do not affect the ability of AR to repress maspin. Ongoing research will continue to investigate AR’s role in the repression of maspin. Understanding the underlying mechanisms by which AR represses maspin and other target genes may reveal novel opportunities for developing new prostate cancer therapies.Item A Study of Mir-210 Affecting Tumor Growth in a Knockout Mouse Model(2012-04-18) Zhang, Shuying