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ItemAn Anti-Influenza Strategy Based on siRNA Approach Targeting the Critical Viral and Host Factors(Georgia Institute of Technology, 2022-05) Liu, TimothyThe influenza virus remains a major public health concern causing significant morbidity and mortality in humans. Vaccination is considered the most effective prevention strategy as antivirals are suboptimal in treating the disease. Several studies have identified numerous host and viral factors utilized by the virus to successfully complete its life cycle. This study performed to investigate the effect of siRNA against two host factors, RanBP5 and CCT, and three viral proteins that make up the viral RNA polymerase (RNAP), PA, PB1, and PB2, in inhibiting the replication of diverse strains and subtypes of influenza virus. The effect of single and combinatorial siRNA on the replication of two influenza A viruses (IAV) and one influenza B virus (IBV) was evaluated in vitro in MDCK cells. siRNA against viral RNAP subunits effectively inhibits growth of both IAV and IBV. Our results further demonstrates that trafficking of the RNAP requires two host proteins, RANBP5 and CCT, with RANBP5 preferentially required for IAV and CCT required for IBV. Our results suggest that a combination of siRNA to RNAP and host import proteins is a potential prophylactic and therapeutic candidate for further development and future in vivo studies.
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ItemNeuron-SpecificC Enolase as a Diagnostic Biomarker for TBI in Preclinical Trials: A systematic review(Georgia Institute of Technology, 2019-05-16) Sofia, Connor J.Traumatic brain injury (TBI) is the leading cause of death and disability among young adults. Thus, discovering a biomarker to assess the severity of TBI is an issue of immense clinical importance. This systematic review aims to evaluate the potential for neuron specific enolase (NSE) to identify TBI in animal studies. MEDLINE and Pubmed were searched for relevant literature up to January of 2017. Studies were included as part of the review if they included animal species, age, sex, injury severity, injury model, sampling site, number of animals per injury group, at least one outcome measure, and number of time points for recording the biomarker in question. Risk of bias was assessed by the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). 3411 citations were screened, of which 20 were considered for final review. NSE was generally found to be a positive predictor for TBI. In preclinical trial data involving TBI, increased levels of NSE correlate with injury severity. Inconsistent data reporting standards and lack of consistency involving injury model hampered the success of this review; more trials with homogeneous data is required to attain statistical significance.
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ItemEvaluating Activity and Sleep Tracking Technologies for Older Adults(Georgia Institute of Technology, 2016-07-18) Burton, Kendall ElizabethThere are currently over 99 million citizens in the United States who are age 50 and older. Many of these older adults are interested in independently maintaining their mental and physical well-being. There are various technologies such as activity and sleep tracking technologies that can help the growing population maintain their health independently. The purpose of this study was to understand user interactions and opinions from an older adult sample (age 50 and older) regarding the ease of use and personal value of seven different activity and sleep tracking technologies. Ninety-two participants used one of the following devices: Fitbit Charge, Misfit Flash, Withings Pulse O2, Withings Activité Pop, Spire, Jawbone UP24, or LumoLift during the study. Over the course of six weeks, participants used the device and documented their use through diary entries. The study concluded with an interview to understand the overall experience as well as the users’ specific likes and dislikes of the technology. Participants completed additional questionnaires to document their technology experience and opinions, exercise motivation, self-efficacy, and locus of control. Overall, 77% of the participants felt that activity and sleep tracking technologies they were assigned were useful or could be useful. Seventy-one percent became more aware of their activity and sleep patterns with 46% stating they actually became more active, slept better, or at more healthily because of the tracker. However, 55% of users found perceived inaccuracy of data to be the largest frustration with the technology and also faced challenges when it came to finding and reading the instructions and wearing the devices. The results of this study focus on several different features of activity and sleep tracking technologies and how they can be improved to help older adults independently monitor their health.
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ItemEffects of HIV-1 Infection on Bone Growth in HIV-1 Transgenic Rats(Georgia Institute of Technology, 2016-01-25) Cavallaro, Alexandra GiovannaHuman immunodeficiency virus (HIV) is a subgroup of a retrovirus that causes acquired immunodeficiency syndrome (AIDS), which is a progressive failure of the immune system. Millions of dollars have been donated for the research of HIV and how the virus works and effects the different systems of the body. HIV infects cells that are crucial components to the immune system and therefore eventually leads to the loss of cell-mediated immunity if left untreated. The structure of the HIV retrovirus consists of two copies of single-stranded RNA, which produces the nine proteins that HIV expresses. Since HIV enters a wide range of cells, multiple tissues are negatively altered. Previous research determined the HIV-1 Transgenic (Tg) rat is an appropriate model for experimentation due to the fact that HIV-1 viral genes they expressed as well as the immune system’s response to outside invaders was very similar to humans. To determine the effects of HIV proteins, bone histomorphometry was analyzed by taking micron samples of the harvested cortical bones. Comparing the fluorescent bands in the cortical bone allowed the bone formation rate to be determined. CT (computed tomography) scans were taken while rats were still alive to give a visual representation of the bone. From evaluating microCT scans, data was collected to prove the individual cortical bone measurements in HIV-1 Tg rats are significantly less than the control WT rats.
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ItemType I versus type II cytokine levels as a function of SOD1 G93A mouse amyotrophic lateral sclerosis disease progression(Georgia Institute of Technology, 2016-01-25) McKissick, Eric A.Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease that is characterized by the degradation of neurons throughout the central nervous system. Inflammation have been cited a key contributor to ALS neurodegeneration, but the timeline of cytokine upregulation remains unresolved. The goal of this study was to temporally examine the correlation between the varying levels of pro-inflammatory type I cytokines (IL-1β, IL-1α, IL-12, TNF-α, and GFAP) and anti-inflammatory type II cytokines (IL-4, IL-6, IL-10) throughout the progression of ALS in the SOD1 G93A mouse model. Cytokine level data from high copy SOD1 G93A transgenic mice was collected from 66 peer-reviewed studies. For each corresponding experimental time point, the ratio of transgenic to wild type (TG/WT) cytokine was calculated. One-way ANOVA and t-tests with Bonferonni correction were used to analyze the data. Meta-analysis was performed for four discrete stages: early, pre-onset, post-onset, and end stage. A significant increase in TG cytokine levels was found when compared to WT cytokine levels across the entire SOD1 G93A lifespan for majority of the cytokines. The rates of change of the individual cytokines, and type I and type II were not significantly different; however, the mean fold change of type I was expressed at significantly higher levels than type II levels across all stages with the difference between the means becoming more pronounced at the end stage. An overexpression of cytokines occurred both before and after the onset of ALS symptoms. The trend between pro-inflammatory type I and type II cytokine mean levels indicate a progressive instability of the dynamic balance between pro- and anti-inflammatory cytokines as anti-inflammatory cytokines fail to mediate the pronounced increase in pro-inflammatory cytokines. Very early immunoregulatory treatment is necessary to successfully interrupt ALS-induced neuroinflammation.