Project BandAid: An Analysis of Preventive Health Knowledge Retention Among Elementary Students in Phoenix

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Description
Within our current educational infrastructure, there’s a lack of substantial preventive care knowledge present among elementary schoolchildren. With education cuts occurring statewide, many schools are left impoverished and schools are incapable of implementing various programs to benefit their local communities.

Within our current educational infrastructure, there’s a lack of substantial preventive care knowledge present among elementary schoolchildren. With education cuts occurring statewide, many schools are left impoverished and schools are incapable of implementing various programs to benefit their local communities. This endeavor aims to visit public and charter elementary schools in the Phoenix Valley to educate youth regarding easily avoidable health risks by implementing healthy eating habits and exercise. Project BandAid will immerse students ages 7-9 in hands-on activities to enhance their knowledge on hygiene, healthy eating habits, and safety. This project incorporated funding from the Woodside Community Action Grant and Barrett, the Honors College as well as the help from Alpha Epsilon Delta (AED) volunteers.
Date Created
2019-05
Agent

Novel Aminoglycoside Polymers and Combination Treatments in Triple Negative Breast Cancer Studies

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Description
In the United States, 12% of women are typically diagnosed with breast cancer, where 20-30% of these cases are identified as Triple Negative Breast Cancer (TNBC). In the state of Arizona, 810 deaths occur due to breast cancer and more than 4,600

In the United States, 12% of women are typically diagnosed with breast cancer, where 20-30% of these cases are identified as Triple Negative Breast Cancer (TNBC). In the state of Arizona, 810 deaths occur due to breast cancer and more than 4,600 cases are diagnosed every year (American Cancer Society). The lack of estrogen, progesterone, and HER2 receptors in TNBC makes discovery of targeted therapies further challenging. To tackle this issue, a novel multi-component drug vehicle is presented. Previously, we have shown that mitoxantrone, a DNA damaging drug, can sensitize TNBC cells to TRAIL, which is a protein that can selectively kill cancer cells. In this current study, we have formulated aminoglycoside-derived nanoparticles (liposomes) loaded with mitoxantrone, PARP inhibitors, for delivery to cancer cells. PARP inhibitors are helpful in preventing cancer cells from repairing their DNA following damage with other drugs (e.g. mitoxantrone). Various treatment liposome groups, consisting of lipid-containing polymers (lipopolymers) synthesized in our laboratory, were formulated and characterized for their size, surface charge, and stability. PARP inhibitors and treatment of cells for in-vitro and in-vivo experiments with these liposomes resulted in synergistic death of cancer cells. Finally, studies to evaluate the pre-clinical efficacy of these approaches using immuno-deficient mouse models of TNBC disease have been initiated.
Date Created
2018
Agent

MicroRNA Function and Role in Splenocyte ST2 Expression via Cellular Transfection

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Description
Stroke is a devastating disease that affects thousands of individuals each year. Stroke, specifically cerebral ischemia, and immune responses are important areas of study and focus. Previous studies on stroke in mouse models had shown the upregulation of a specific

Stroke is a devastating disease that affects thousands of individuals each year. Stroke, specifically cerebral ischemia, and immune responses are important areas of study and focus. Previous studies on stroke in mouse models had shown the upregulation of a specific micro-RNA: miR-1224. We hypothesized that miR-1224 was responsible for the regulation of the ST2 receptor protein’s expression. We performed cellular transfection on murine splenocytes with four different miRNAs—miR-1224-mimic, miR-1224-inhibitor, miR-451-mimic, and a control. We predicted that transfection with 1224m would decrease ST2 expression, while transfection with 1224i would increase ST2 expression. Two complete trials were run, and analysis of the results included RT-PCR of both miRNA samples and mRNA samples to confirm transfection and controlled transcription. Reverse transcription and qPCR of miRNA was done in order to confirm that transfection was in fact successful. Reverse transcription and qPCR of the mRNA was done in order to confirm that ST2 mRNA was not altered; this allowed us to attribute any changes in ST2 protein levels to miRNA interactions, as the mRNA levels were consistent. Western blotting was done in order to assess relative protein content. We found that transfection with 1224m slightly decreased ST2 expression and transfection with 1224i slightly increased ST2 expression, however, after assessing the p-values through statistical analyses, neither difference was significant. As such, our hypothesis was rejected as it is not evident that miR-1224 plays a significant role on ST2 gene expression. Future studies are needed in order to analyze alternate protein targets to fully assess the role of miR-1224.
Date Created
2018-05
Agent

Sequence-Specific Detection of Different Strains of LCMV in a Single Sample Using Tentacle Probes

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Description

Background: Virus infections often result in quasispecies of viral strains that can have dramatic impacts on disease outcomes. However, sequencing of viruses to determine strain composition is time consuming and often cost-prohibitive. Rapid, cost-effective methods are needed for accurate measurement of

Background: Virus infections often result in quasispecies of viral strains that can have dramatic impacts on disease outcomes. However, sequencing of viruses to determine strain composition is time consuming and often cost-prohibitive. Rapid, cost-effective methods are needed for accurate measurement of virus diversity to understand virus evolution and can be useful for experimental systems.

Methods: We have developed a novel molecular method for sequence-specific detection of RNA virus genetic variants called Tentacle Probes. The probes are modified molecular beacons that have dramatically improved false positive rates and specificity in routine qPCR. To validate this approach, we have designed Tentacle Probes for two different strains of Lymphocytic Choriomeningitis Virus (LCMV) that differ by only 3 nucleotide substitutions, the parental Armstrong and the more virulent Clone-13 strain. One of these mutations is a missense mutation in the receptor protein GP1 that leads to the Armstrong strain to cause an acute infection and Clone-13 to cause a chronic infection instead. The probes were designed using thermodynamic calculations for hybridization between target or non-target sequences and the probe.

Results: Using this approach, we were able to distinguish these two strains of LCMV individually by a single nucleotide mutation. The assay showed high reproducibility among different concentrations of viral cDNA, as well as high specificity and sensitivity, especially for the Clone-13 Tentacle Probe. Furthermore, in virus mixing experiments we were able to detect less than 10% of Clone-13 cDNA diluted in Armstrong cDNA.

Conclusions: Thus, we have developed a fast, cost-effective approach for identifying Clone-13 strain in a mix of other LCMV strains.

Date Created
2017-10-13
Agent

Portable and Low-Cost Detection Platform for Hepatitis B Virus Infections

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Description
Approximately 248 million people in the world are currently living with chronic Hepatitis B virus (HBV) infection. HBV and HCV infections are the primary cause of liver diseases such as cirrhosis and hepatocellular carcinomas in the world with an estimated

Approximately 248 million people in the world are currently living with chronic Hepatitis B virus (HBV) infection. HBV and HCV infections are the primary cause of liver diseases such as cirrhosis and hepatocellular carcinomas in the world with an estimated 1.4 million deaths annually. HBV in the Republic of Peru was used as a case study of an emerging and rapidly spreading disease in a developing nation. Wherein, clinical diagnosis of HBV infections in at-risk communities such the Amazon Region and the Andes Mountains are challenging due to a myriad of reasons. High prices of clinical diagnosis and limited access to treatment are alone the most significant deterrent for individuals living in at-risk communities to get the much need help. Additionally, limited testing facilities, lack of adequate testing policies or national guidelines, poor laboratory capacity, resource-limited settings, geographical isolation, and public mistrust are among the chief reasons for low HBV testing. Although, preventative vaccination programs deployed by the Peruvian health officials have reduced the number of infected individuals by year and region. To significantly reduce or eradicate HBV in hyperendemic areas and countries such as Peru, preventative clinical diagnosis and vaccination programs are an absolute necessity. Consequently, the need for a portable low-priced diagnostic platform for the detection of HBV and other diseases is substantial and urgent not only in Peru but worldwide. Some of these concerns were addressed by designing a low-cost, rapid detection platform. In that, an immunosignature technology (IMST) slide used to test for reactivity against the presence of antibodies in the serum-sample was used to test for picture resolution and clarity. IMST slides were scanned using a smartphone camera placed on top of the designed device housing a circuit of 32 LED lights at 647 nm, an optical magnifier at 15X, and a linear polarizing film sheet. Tow 9V batteries powered the scanning device LED circuit ensuring enough lighting. The resulting pictures from the first prototype showed that by lighting the device at 647 nm and using a smartphone camera, the camera could capture high-resolution images. These results conclusively indicate that with any modern smartphone camera, a small box lighted to 647 nm, and optical magnifier; a powerful and expensive laboratory scanning machine can be replaced by another that is inexpensive, portable and ready to use anywhere.
Date Created
2018-05
Agent

Intramyocellular Lipids and the Progression of Muscular Insulin Resistance

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Description
Diabetes is a disease characterized by reduced insulin action and secretion, leading to elevated blood glucose. In the 1990s, studies showed that intravenous injection of fatty acids led to a sharp negative response in insulin action that subsided hours after

Diabetes is a disease characterized by reduced insulin action and secretion, leading to elevated blood glucose. In the 1990s, studies showed that intravenous injection of fatty acids led to a sharp negative response in insulin action that subsided hours after the injection. The molecule associated with diminished insulin signalling response was a byproduct of fatty acids, diacylglycerol. This dissertation is focused on the formulation of a model built around the known mechanisms of glucose and fatty acid storage and metabolism within myocytes, as well as downstream effects of diacylglycerol on insulin action. Data from euglycemic-hyperinsulinemic clamp with fatty acid infusion studies are used to validate the qualitative behavior of the model and estimate parameters. The model closely matches clinical data and suggests a new metric to determine quantitative measurements of insulin action downregulation. Analysis and numerical simulation of the long term, piecewise smooth system of ordinary differential equations demonstrates a discontinuous bifurcation implicating nutrient excess as a driver of muscular insulin resistance.
Date Created
2017
Agent

Linking Immunologic and Epidemiologic Models of Virus Transmission and Susceptibility

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Description
Memory CD8+ T-cells can persist in the absence of antigen, primed for immediate activation and proliferation if later exposed to the same antigen. These cytotoxic lymphocytes provide long-term immunity following an acute infection. Studies have observed that intermediate levels of

Memory CD8+ T-cells can persist in the absence of antigen, primed for immediate activation and proliferation if later exposed to the same antigen. These cytotoxic lymphocytes provide long-term immunity following an acute infection. Studies have observed that intermediate levels of general T cell transfer prior to infection may cause an inappropriate response resulting in increased pathology rather than prevention. Therefore, our study focused on a memory CD8 T-cell therapy using lymphocytic choriomeningitis virus (LCMV) specific splenocytes, which activate and proliferate at an accelerated pace compared to that of naive T-cells. LCMV is a natural murine pathogen which also poses a zoonotic infection threat to humans, and the effect of immune cell vaccination therapies for LCMV is not fully understood. We observed the effect of multiple memory CD8 T cell dosage levels on overall disease and memory CD8 T-cell response to the virus. Infection by exposure to a carrier was shown to have a reduced impact on mice receiving higher doses of memory T cells prior to infection compared to mice receiving less or no memory cells. Higher presence of activated memory cells were shown to correlate with less disease-related weight loss and accelerated recovery times. Survival rate after exposure to carriers was not shown to be affected by dosage level, warranting further research regarding the prevalence of the immunopathology observed in other studies in natural murine transmission models.
Date Created
2016-05
Agent

Establishing a murine model for congenital LCMV infection

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Description
Pathogens such as lymphocytic choriomeningitis virus (LCMV) cause abnormalities in the nervous system of developing mice and humans. While humans are able to recover from infection and clear the virus, the mouse immune system tolerates the virus and lifelong infection

Pathogens such as lymphocytic choriomeningitis virus (LCMV) cause abnormalities in the nervous system of developing mice and humans. While humans are able to recover from infection and clear the virus, the mouse immune system tolerates the virus and lifelong infection ensues. In order to understand the factors driving LCMV evolution and evaluate its neuropathogenesis, a mouse model was needed. To establish congenital infection, newborn C57BL/6J mice were intra-cerebrally (i.c.) injected with 1 x 103 PFU LCMV Armstrong. Mice failed to thrive, resulting in a linear reduction in survival over the following two weeks and overall survival of 13%. Surviving mice did not have virus in their circulation after thirty days. As an alternative, 500 PFU of LCMV Armstrong was injected intraperitoneally (i.p.) into other litters. While this was associated with significantly reduced mortality, no mice in this group developed persistent infection either. ELISAs revealed that the mothers of injected pups developed a robust humoral response, confirming earlier reports that contact-associated acute infection occurs (Hotchin, 1971). In addition, the offspring of two litters of mice (out of six tested) also had antibodies to the virus, but at slightly lower titers. This indicates that the humoral response of the mothers may play a role in the neonatal clearance of infection. A higher titer of LCMV in i.p. injections may be necessary to overcome these barriers and establish chronic infection. In contrast, a lower dose of LCMV is recommended for i.c. injections, as the mortality seemed directly linked to the effects of the virus on offspring growth and development. Exposure to the virus in utero may also be necessary to increase survival and the likelihood of chronic infection.
Date Created
2016-05
Agent

Genetic Trends in the Vertical Transmission of the Clone-13 Variant of LCMV

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Description
Among wild rodent populations, vertical transmission is believed to constitute the primary route of infection for Lymphocytic Choriomeningitis Virus (LCMV), a non-lytic arenavirus with both acute and chronic forms. When carrier mice infected at birth with the acute Armstrong strain

Among wild rodent populations, vertical transmission is believed to constitute the primary route of infection for Lymphocytic Choriomeningitis Virus (LCMV), a non-lytic arenavirus with both acute and chronic forms. When carrier mice infected at birth with the acute Armstrong strain reproduce, they generate congenital carrier offspring containing a quasispecies of LCMV that includes Armstrong as well as its chronic Clone-13 variant. This study examined the genetic trends in the vertical transmission of LCMV from mothers infected perinatally with Clone-13. Viral isolates obtained from the serum of congenital carrier offspring were partially sequenced to reveal residue 260 in the glycoprotein-encoding region of their S segment, the site of a major amino acid change differentiating the chronic and acute strains. It was found that the phenylalanine-to-leucine mutation associated with Clone-13 was present in 100% of the isolates, strongly indicating that the offspring of Clone-13 carriers contain exclusively the chronic variant. This research has broad implications for the epidemiology of the virus, and, given the predominance of Armstrong in the wild, suggests that there must be a biological cost associated with Clone-13 infection in non-carriers.
Date Created
2015-05
Agent

On the dynamics of dengue virus type 2 with residence times and vertical transmission

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Description
A two-patch mathematical model of Dengue virus type 2 (DENV-2) that accounts for vectors’ vertical transmission and between patches human dispersal is introduced. Dispersal is modelled via a Lagrangian approach. A host-patch residence-times basic reproduction number is derived and conditions

A two-patch mathematical model of Dengue virus type 2 (DENV-2) that accounts for vectors’ vertical transmission and between patches human dispersal is introduced. Dispersal is modelled via a Lagrangian approach. A host-patch residence-times basic reproduction number is derived and conditions under which the disease dies out or persists are established. Analytical and numerical results highlight the role of hosts’ dispersal in mitigating or exacerbating disease dynamics. The framework is used to explore dengue dynamics using, as a starting point, the 2002 outbreak in the state of Colima, Mexico.
Date Created
2016-08-05