Tucker Stuart

Biosymbiotic, Personalized and Digitally Manufactured Wireless Devices for Indefinite Collection of High-Fidelity Biosignals.

Tucker Stuart, University of Arizona, Graduate Student

Digital medicine, the ability to measure heath status precisely and continuously, is pivotal for the next generation of devices aimed at disease diagnosis, management, and treatment. Current digital devices are not suitable for long-term continuous data acquisition due to their use of limited power supplies and subsequent increase in mass, resulting in patient discomfort and poor sensing interfaces. To address this, we have developed a soft, mesh-structured wearable device that relies on far-field power transfer and ultra-soft, ultra-thin electronics systems to deliver a wireless and battery-free platform capable of operating at long distances and delivering uninterrupted, high-fidelity data streams. These systems are digitally manufactured and customizable to meet the individual needs of the patient with demonstrations of novel sensing solutions for varying disease paradigms.

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Saathvika Vegasina

Investigating the MS4A1 and MFN2 genes’ correlation with mTORC2 in Melanoma

Saathvika Vegasina, Paradise Valley High School High School, High School Student

Metastasis is the spread of cancer in the host’s body. Cell migration is a major part of cancer metastasis. In mammals, the mechanistic Target of Rapamycin Complex 2 (mTOCR2) is a protein kinase complex known for regulating cell migration. By using the cBioportal database, we looked for genes in melanoma tumor tissue samples that have shown to have a correlation with the S473 phosphorylation of AKT, which suggests mTORC2 activity. I decided to investigate the correlation between MS4A1 and MFN2 with mTORC2 in melanoma. MS4A1 is a gene which encodes for the protein CD20 which has shown an alteration in cell migration when present in immune cells. The Chi-square test resulted with a significant p-value which shows that MS4A1 has a negative correlation with the regulation of mTORC2 in melanoma. The correlation with MS4A1 suggests that melanoma cancer cells may be co-opting pathways which are present in immune cells. MFN2 has shown to have a correlation with mTORC2 in breast cancer and lung cancer; however, based on the Chi-squared test results, MFN2 has shown to have no correlation with mTORC2 in melanoma. With the conclusions gained from our project, we can further investigate the relationship between MS4A1 and MFN2 genes in a laboratory setting in order to develop therapeutic strategies to prevent the spread of cancer.

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Rebecca Jernigan

Structural and functional studies of prophylactic drug target, NendoU, from SARS-CoV-2 for time-resolved serial femtosecond crystallography and rational drug design

Rebecca Jernigan, Arizona State University, Graduate Student

Nonstructural protein 15 (Nsp15) is a Uridine specific nidoviral endoribonuclease (often called NendoU) from the SARS-CoV-2 virus, the causative agent of the COVID-19 pandemic. NendoU aides in the evasion of the host immune system by degrading the poly-uridine (Poly-U) leader sequence on the anti-sense viral RNA. Loss of activity in NendoU would leave the Poly-U leaders intact, which has been shown to have an earlier and more robust immune response, making NendoU an attractive prophylactic drug target against COVID-19.The goal of the project is to determine the first snapshots of NendoU’s catalytic mechanism by time-resolved serial femtosecond (fs) crystallography (TR-SFX). In this poster, we present the first results of the active NendoU/citrate structure solved to 2.6 degrees at room temperature at the Linac Coherent Light Source (LCLS) X-ray Free Electron Laser (XFEL) at the Stanford Linear Accelerator Center (SLAC). The H234A inactive mutant for RNA docking was solved to 4.7, also under SFX conditions at LCLS. These experiments demonstrate successful diffraction of NendoU microcrystals at LCLS and structural analysis reveals that the active site is well positioned in the solvent channel to allow for diffusion of the enzyme. Additionally, RNA substrate (5 and 21 nucleotides) was designed using analysis of the NendoU active site and sequence analysis of the viral RNA substrate. NendoU microcrystals were shown to remain active and cleave the RNA substrate, required for proposed TR-SFX experiments. In addition to the new structural and functional information provided in this studies, the exact conditions for performing TR-SFX were established. Using microfluidic mix-and-inject devices, NendoU microcrystals will be mixed with RNA substrate at millisecond time points. The ultra fast time points can only be solved using the brilliance and timescales achieved by an XFEL, making the experimentation process extremely competitive. By solving the structure at different time points, we hope to assemble a ‘molecular movie’ that directly observes substrate binding, cleavage, and release. This information would be a major advance in understanding the biology of NendoU as well as identifying important conformational changes and sites that could be used to inhibit the structural mechanism, and therefore its function of evading the coronavirus infection from the host immune system. Optimization of existing drugs and novel drug development would benefit those infected or exposed to the SARS-CoV-2 virus and would provide an additional direction for COVID-19 treatment, not previously used. Because NendoU is highly conserved across the Coronaviridae family, it also is promising for new variants and future coronaviruses, as it is not very prone to large or rapid changes.

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Nathaniel Gallegos

Gray Matter Volumetric Differences in Healthy Older Adults at Risk for Alzheimer’s Disease

Nathaniel Gallegos, University of Arizona, Graduate Student

It is well-documented that gray matter volume decreases in Alzheimer’s disease (AD). Gray matter volumes have been shown to be correlated with disease progression and cognitive deficits. These brain changes can be detected in some of the earlies stages of this disease, such as the preclinical stages where there are no cognitive symptoms of AD.

In this study, we investigated gray matter volume loss in individuals who are at high risk of developing AD based on several risk factors, including carrying the apolipoprotein e4 allele (APOE-4) or having a first-degree family history of AD. We analyzed the gray matter volumes in 46 cognitively healthy older adults, ages 49 to 89 with an average of 70 years, with one or both risk factors, and an additional 32 matched controls without either risk factor.

Voxel-based morphometry of high-resolution MRI showed significantly smaller gray matter volumes in risk groups compared to controls in a region of the left anterior hippocampus, as well as other brain regions including the left temporal pole and the right superior frontal gyrus. Those in the risk group also scored significantly lower on Trails B and the California Verbal Learning Test compared to those in the no-risk group.

This study provides evidence that these risk factors have an influence on gray matter volumes and show a detectable effect on cognition even in cognitively healthy individuals.

Subsequent analyses will determine which of the risk factors are driving these differences.

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Morgan Snider

UPTAKE HYDROGENASE IN CYANOBACTERIA

Morgan Snider, Grand Canyon University. Undergraduate Student

Photoautotrophic prokaryotic cyanobacteria are ideal models for microbial hydrogen production. Hydrogen is produced by nitrogenase and bidirectional hydrogenase. Uptake hydrogenase reduces the net gain of H2 through oxidation. The two genes that encode the subunits of uptake hydrogenase are hupS and hupL. Genetic deletion of it could greatly increase hydrogen production by cyanobacteria, and it will be the focus of this presentation.

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Marina Hu

Data Analysis for Frequency of Terms Indicating Autism Spectrum Disorder (ASD)

Marina Hu, BASIS Chandler High School

Behavior, Anorexia, and Obsessive-Compulsive Disorder (OCD) in ASD Electronic Health Records (EHRs).

In the US, boys are four times more likely to get diagnosed with Autism Spectrum Disorder (ASD) than girls. We focused on two possible explanations for this disparity: some ASD symptoms for girls overlap with other diseases such as Anorexia and Obsessive-Compulsive Disorder (OCD), and boys’ behaviors are examined more comprehensively when evaluated for ASD compared to girls. To investigate these hypotheses, we applied Natural Language Processing (NLP) to 4480 Electronic Health Records (EHRs), the Arizona dataset of a 2000-2010 CDC surveillance project. We created a Java program to count the number of terms indicating Anorexia, OCD, and ASD-Behavior (such as “play”, “alone”, “repetition”, etc.) in the EHRs and compared the counts between boys and girls. We found that terms indicating Anorexia appeared two times more frequently in girls’ EHRs than in boys’, while terms indicating OCD appeared 12.2% greater in boys’ EHRs than girls’. Additionally, the average of total behavior words per boy EHR was 14.9% greater than that of girls. Our results suggest that girls evaluated for ASD tend to also be considered for Anorexia but not so much with OCD, and that behavior words show up more frequently in boys’ EHRs than girls’. These results provide potential explanations for the disparity in ASD diagnosis between boys and girls. More research is needed to verify if girls are also considered for just Anorexia or any other diseases and if behavior words appear at similar frequencies in national datasets of ASD EHRs.

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Katherine Wei

Integrated Analysis of the Association Between Alzheimer’s Disease and Cardiovascular Disease

Katherine Wei, BASIS Chandler High School, High School Student

Alzheimer’s Disease (AD), the sixth leading cause of death in the US, and cardiovascular disease (CVD), the first leading cause of death in the US, are frequently associated. Past studies hypothesize that amyloid deposits damage organs, causing this association. Examining how vascular factors can influence AD pathogenesis can help in understanding the link between the blood to the brain, which can provide alternative paths of exploration for disease treatment. This study analyzes gene expression and shared biological processes between AD and CVD, specifically myocardial infarction and heart failure, via bioinformatic approaches and published datasets from the Gene Expression Omnibus (GEO). First, 73 differentially expressed genes (DEGs) were identified among four datasets using blood samples from AD and CVD patients. Panther’s Gene Ontology Analysis validated several biological processes such as xylulose biosynthetic process and toll-like receptor TLR1:TLR2 signaling pathway along with molecular functions, cellular components, and pathways to be significantly enriched in the list of 73 DEGs. Analysis of protein-protein interactions and the associated gene network indicated that from the list of 73 DEGs, only six (MAPK14, TLR2, HCK, GRB2, PRKCD, PTPN6) had eight or more degrees. Next, those six genes were identified in a normalized dataset containing different brain regions of AD and non-AD patients. Two-sample t-tests for differences in mean showed statistically significant differences in GRB2 and PRKCD, supporting a blood-brain relationship in the association between AD and CVD. This study can help in developing new medications to target AD and CVD susceptible genes.

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Justus Nwachukwu

Supramolecular Assembly of Redox Proteins to form Nanowires for Ultra-Long-Range Biological Electron Transfer

Justus Nwachukwu, Arizona State University, Graduate Student

Supramolecular Assembly of Redox Proteins to form Nanowires for Ultra-Long-Range Biological Electron Transfer

J. N. Nwachukwu, M. A. Thirmurthy, J. T. Atkinson, M. Y. El-Naggar and A. K. Jones

Exoelectrogenic organisms transfer electrons from their internal quinone pool to extracellular acceptors over nano-scale distances through appendages known as “biological nanowires.” These structures have been variously described as cytochrome-rich membrane extensions or pili, and the components and mechanisms of this long-range electron transfer remain largely unknown. In fact, current physical understanding of biological electron transfer is only sufficient to describe electron movement on the nm scale. This presentation will describe a proteinaceous, supramolecular model for ultralong-range biological electron transfer. This supramolecular structure is based on a self-assembling peptide. To facilitate assembly, a small redox protein from Shewanella oneidensis, a model exoelectrogen, is fused to the peptide component which can be combined with free peptide to assemble a fibrillar structure. Assembled nanowires have average dimensions of 500 nm, 15 nm by 9 nm. Electrochemical measurements show the nanowires retain the native reduction potential of their constituent protein, and electrochemical gating results suggest electrical conductivity occurs along the length of these structures via a cytochrome-mediated electron transfer.

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Joseph Rice

HYDROGEN PRODUCTION BY CYANOBACTERIUM ANABAENA VARIABILIS

Joseph Rice, Grand Canyon University, Undergraduate Students
Anabaena variabilis ATCC 29413 is a filamentous strain of cyanobacteria which separates nitrogen fixation from photosynthesis spatially by producing specialized anoxic cells called heterocysts. This study aims to characterize A. variabilis for the purpose of evaluating the environmental factors that affect its nitrogenase activity and hydrogen production in comparison to the unicellular strain of Synechocystis sp. PCC 6803. The biotechnological application of this work is the production of biofuels.

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Isabel Ross

Green Infrastructure Impacts on Carbon Cycling: Evaluating Changes in Soil Microbial Composition and Function

Isabel Ross, Cienega High School, High School Student

This project aimed to identify how the implementation of green infrastructure (GI) water harvesting systems impacts the carbon cycle by studying shifts in microbial composition and function. To conduct this study, we created a GI system in a residential area in Tucson, Arizona. We identified the microbes present in the soil by sequencing a 16S rRNA gene marker and using a program called FAPROTAX. This program mapped the identified microbes to associated functions. I then conducted a literature review to link the identified microbes to functions they have been proven to perform. I focused on two functions involved in the breakdown of cell walls and exoskeletons, making them key for decomposition: chitinolysis and cellulolysis. I found that both functions have higher abundances in all GI systems compared to the control. This demonstrates that GI water harvesting treatments do impact soil microbial composition and function. This is important because it suggests that GI does alter the carbon cycle, which could have possible impacts on climate change, as carbon is a major greenhouse gas. In addition, GI systems may increase the availability of key nutrients by releasing locked compounds stored behind strong cell walls, exoskeletons, and cellulose. Increases in bioavailable compounds can lead to greater access by other organisms such as soil invertebrates and plants supporting growth and increased diversity.

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