Browsing by Subject "Biology Program"

Now showing 1 - 10 of 10
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    Cold Adaptation and Mitochondrial Function in S. cerevisiae
    (2011-02-22) Leeaw, Phoebe
    A major theory concerning the origin of life proposes that the first cells arose in cold, rather than hot, conditions. Regardless of its origin, life today can be found throughout the entire globe, even at the poles. Consequently, for survival to be possible, organisms must be capable of energy production under extreme temperatures. The main focus of this study is to determine the genetic basis of the ability of cells to grow at low temperatures. Yeasts are capable of fermentation in cold environments, but the effect of extreme temperatures on respiration is still under investigation. The objective of the experiment was to determine if S. cerevisiae mitochondrial function is important for growth at low temperatures. To test this hypothesis, we screened cold-sensitive mutants for their ability to grow on media that can only be metabolized via respiration. If the mutant gene is important for mitochondrial biogenesis or function, then its deletion may also hinder oxidative phosphorylation. Yeast mutants were grown in conditions at permissive and cold temperatures to observe differences in growth patterns. Our preliminary results suggest that most genes required for growth at low temperature do not affect mitochondrial function. Thus, most cold-sensitive mutants have robust mitochondrial function indicating that their inability to grow at low temperatures does not reflect an underlying mitochondrial defect.
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    Effect of Experimental Drug S107 on Accessory Protein Binding to the RyR
    (2012-04-18) Popa, Mircea Anton
    The physiological basis of muscle-generated motor activity depends on the precise regulation of intracellular Ca2+ ions. Central to this process is the sarcoplasmic reticulum (SR), a special organelle in muscle cells that is responsible for ion storage. The Ca2+ ions are released from the SR through a large conductance channel known as the ryanodine receptor (RyR). The channel’s activity is in turn regulated by intracellular messengers, including FK506 binding proteins (FKBP12.6 & 12.0), and calmodulin (CaM). The experimental heart failure drug S107 has been associated with improved muscle performance, though it is still unclear if it directly affects the binding activity of either the FKBPs or CaM. Here, the effect of S107 on the binding of fluorescent FKBPs and CaM to RyR is characterized. The results show that S107 slightly, but significantly, decreases the binding affinity of CaM; though, only in nanomolar calcium concentrations, and when the RyR is treated with oxidized glutathione. S107 has no significant effect on the binding of FKBP to RyR. Prior to this research, it was thought that S107 might significantly increase the binding affinity of FKBP. The effect of S107 on CaM binding to RyR has not been previously investigated. These results suggest that the primary mechanism through which S107 achieves its physiological effects does not require or affect FKBP binding. Further studies will have to determine whether the effect of S107 on CaM binding to RyR is linked to the inhibition of Ca2+ leak in the channel.
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    Evaluation of Inferior Alveolar Nerve Position using Cone Beam CT
    (2009-04-08) Koivisto, Tyler
    The introduction of foreign material placed near or into the inferior alveolar nerve during implant placement or root canal therapy can result in altered nerve sensation (paresthesia) or continual pain (dysesthesia). The inferior alveolar nerve is housed in the mandibular canal of the lower jaw (mandible) providing innervations to the lower teeth, and is sensitive to changes in the enviroment. The aim of our study is to measure the distance between the inferior alveolar nerve and the apical root/s of the second premolar, first molar and second molar, and compare the results amongst three age groups: young, middle-age, and older patients. Distances were measured using cone beam computerized tomography (CBCT) radiographs. Cross-sectional images allow visualization of a third dimension, thus providing a more accurate measurement than a two-dimensional radiograph. This data will help dentists avoid surgical complications and better prepare for dental procedures.
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    Exploration of Small Molecule Reduction via Transition Metal Complexes Supported by Novel Trianionic Cryptand Ligand Systems
    (2011-04-13) Mullikin, Alex
    The reductions of small molecules (CO2, CO, N2, and O2) have been studied as an interesting, cheap method for the formation of valuable chemical feedstocks. While prices of petroleum on the rise, processes such as the reduction of CO-2 into methanol are necessary to ease our use from non-renewable sources of fuel. To achieve these reductive processes, my research has been focused on the design and synthesis of novel ligands. Following the synthesis of these novel ligands, they will be metallated with late transition metals (Zn, Co, Fe, and Mn). A Zn complex which is supported by a trianionic, tetradentate cryptand ligand has been synthesized and characterized with X-Ray Crystallography. This metallated ligand, along with the fore mentioned metals, will be reacted with various small molecules and analyzed for the ligand’s ability to reduce these molecules.
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    Exploring the Mechanism of Ara-C Resistance in Acute Myeloid Leukemia
    (2010-04-21) Ellingson, Alexandra M.
    Acute myeloid leukemia (AML) is the most common and most deadly type of leukemia in adults, affecting approximately 3 people per 100,000. AML is typically treated with a cocktail of chemotherapeutic drugs, most often involving the pharmaceutical agent cytosinearabinoside (Ara-C). Treatment with Ara-C will almost always cause remission in AML patients. However, developed resistance to Ara-C becomes a problem for many patients suffering from the disease, and many relapse within a few years of remission. We are using an in vitro system to model the Ara-C resistance in AML cell lines.
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    IL-4 Induces Protection of Porcine Endothelial Cells from Anti-Endothelial Cell Antibody in Association with Upregulation of Claudin-5
    (2010-04-21) Goldish, Danny
    Interspecies organ transplantation offers a potential strategy to the global shortage in vital human organs for donation. Multiple obstacles remain before rejection of foreign organ grafts (xenotransplantation) can be avoided. In pig-to-primate combinations, the vascular endothelium of the transplant is the main target of injury by the host immune system. We are using an in vitro system in which pig endothelial cells (EC) are modified to make them resistant to injury by anti-EC antibodies (abs) in human blood. These abs damage the EC by causing cellular retraction and intercellular gap formation. My aim is to study methods and mechanisms that protect the EC from injury caused by the abs. The cytokine interleukin-4 (IL-4) induces protection of EC from apoptosis and from killing by human complement. My results demonstrated that pretreatment of the EC with pig IL-4 decreases the amount of abinduced cellular retraction and intercellular gap formation. This finding suggested that IL-4 might regulate the expression of proteins that maintain cell-to-cell junctions in the monolayer. Using immunofluoresce, we examined the expression of the junction proteins CD31, VEcadherin, and claudin-5, in IL-4-treated and untreated EC. We found that IL-4 strongly induces claudin-5 expression, but not expression of VE-cadherin or CD31. We now plan to use siRNA silencing of claudin-5 to investigate whether increases in claudin-5 protein are important for protection of EC from ab-induced damage. If this silencing abolishes EC protection, claudin-5 must play a pivotal role in IL-4-induced protection. Conversely, if protection still occurs, claudin-5 is an unnecessary side reaction of the protection. This information will help uncover mechanisms behind IL-4 induced protection, and contribute to new approaches for xenotransplantation.
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    Protection Against Acute Kidney Injury by TUDCA
    (2009-04-08) Ononenyi, Chimezie U.
    Presently there is no therapy for acute kidney injury (AKI). Potentially one can protect kidneys against injury by preventing cell death following AKI. There are two types of cell death that occurs following AKI: necrosis and apoptosis. Necrosis is uncontrolled and synchronous cell death that occurs at the time of AKI. In contrast, apoptosis, or programmed cell death is an asynchronous cell death that continues to occur for days following AKI, thereby providing a window of opportunity for intervention. Tauroursodeoxycholic acid (TUDCA), a bile acid synthesized in the liver, has been shown to be effective by inhibiting apoptosis in rat models of stroke and Huntington’s disease. We hypothesized that TUDCA will be similarly effective in protection against AKI. Accordingly, the goal of this study was to investigate the protective effects of TUDCA in a rat model of ischemic AKI. We induced AKI by bilateral renal artery clamping for 45 minutes. Three rats were given 400mg/kg/day of TUDCA intraperitoneally from day -1 to day 6, while the control animals received the vehicle. We determined kidney functions by measuring blood urea nitrogen (BUN), proliferation by immunohistochemistry for Ki67, and apoptosis by TUNEL assay. Compared to a control, animals that received TUDCA had less severe kidney injury and apoptosis. In conclusion, TUDCA provides protection against acute kidney injury likely by preventing apoptosis.
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    Selection Patterns on HMGR
    (2009-04-08) Biermann, Mitch
    In humans, many infections caused by fungi such as athlete's foot and yeast infections are relatively benign. However, in individuals with compromised immune systems caused by HIV or the use of immunosuppressant drugs, fungal infections are critically life-threatening. Hospital-acquired infections caused by Candida albicans and C. glabrata have a 47 percent mortality rate and an average treatment cost of $40,000 per infection. The incidence of these pathogens has increased in recent years. Targeting fungal pathogens via antifungal drugs is often complicated by the high degree of similarity between molecular machines of fungi and those of their human hosts. Here we propose a potential new target, the enzyme HMG-CoA Reductase (HMGR), by phylogenetic analysis. HMGR catalyzes the rate-limiting step in the production of cholesterol, and the human HMGR has been a fruitful target for drug design, yielding compounds such as Lipitor. Current inhibitors of human HMGR stop fungal growth, but no fungal-specific HMGR inhibitors currently exist. We examined patterns of evolution on 50 HMGR gene sequences to find differences in human and fungal HMGR that could be exploited to make new antifungal compounds. We found one promising target near the enzyme's active site. We plan to design molecular models of the fungal protein based on the known human structure. This model will be used to design drugs likely to specifically inhibit fungal HMGR.
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    Sodium Retention in Mice with Huntington's Disease
    (2009-04-08) Robey, Christa
    Huntington Disease (HD) is a neurodegenerative disease with an autosomal dominant inheritance pattern characterized by late onset, jerking movements, difficulty with reasoning/cognition and change in personality. The exact mechanism of the pathology is not known but current research is focusing on the hypothalamus and the endocrine system. Magnetic resonance spectroscopy (MRS) provided evidence that HD mice had elevated metabolite (esp. sodium) concentrations in their blood, which led Dr. Janet Dubinsky to believe hypernatremia and resulting sodium retention may be the mechanism of brain shrinkage in HD mice. Subsequently, an experiment was designed to observe and analyze the cause and effect of sodium retention in mice with Huntington disease. A change in the metabolic activity of transgenic mice was observed upon the onset of HD, characterized by increased overall water consumption, decrease in urine osmolarity and increase in plasma osmolality.
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    Widespread Recycling in Local Restaurants to Reduce Waste
    (2009-04-08) Block, Lindsay
    Widespread recycling and composting is uncommon in restaurants; everything used is thrown into the garbage, which usually ends up in a landfill. Recycling reduces the amount of waste as well as provides raw material for making new products. Composting naturally increases the nutrient content in soil and reduces greenhouse emissions from landfills. Restaurants in this study produce an average of 30 tons per year of garbage that ends up in a landfill. For three consecutive days the garbage from each of four restaurants was sorted into plastics, metals, glass, paper products, food and other waste. The average percent amount for each component was 5%, 4%, 3%, 25%, 15%, and 18% respectively. Composting food and paper products would decrease the amount of waste added to landfills each year to only 6 tons, which represents a 500% reduction in total landfill accumulation each year. Recycling and composting represents a small, but important step in reducing emissions and protecting the environment.