A Machine Learning Model Of Perturb-Seq Data For Use In Space Flight Gene Expression Profile Analysis, Liam F. Johnson, James Casaletto, Lauren Sanders, Sylvain Costes

Graduate Industrial Research Symposium

The genetic perturbations caused by spaceflight on biological systems tend to have a system-wide effect which is often difficult to deconvolute it into individual signals with specific points of origin. Single cell multi-omic data can provide a profile of the perturbational effects, but does not necessarily indicate the initial point of interference within the network. The objective of this project is to take advantage of large scale and genome-wide perturbational datasets by using them to train a tuned machine learning model that is capable of predicting the effects of unseen perturbations in new data. Perturb-Seq datasets are large libraries of …

Factors Impacting Genetic Test Result Recall And Adherence To Cancer Risk Management Recommendations Among Patients With Germline Pathogenic Variants, Karishma Prakash Bharwani

USF Tampa Graduate Theses and Dissertations

Only 20-60% of information from medical appointments is estimated to be retained of which about half is recalled accurately; however there remains limited information about recall following disclosure of inherited cancer genetic test results (GTR). We sought to evaluate recall of GTRs and the association of recall with adherence to recommended cancer risk management (CRM). Study participants were consented individuals with a confirmed germline pathogenic or likely pathogenic variant (GPV) in an inherited cancer predisposing genes for which there are CRM guidelines per the National Comprehensive Cancer Network (NCCN). Through information collected through self-reported surveys, adherence to CRM was defined …

Species Delimitation Of Slimy Salamanders, Plethodon Kisatchie And Plethodon Mississippi, Across The Lower Mississippi River, Brock Hunter Stevenson

Master's Theses

Species are fundamental units of biodiversity yet delimiting species can be challenging. Slimy Salamanders of the Plethodon glutinosus species complex are a classic example of cryptic species for which species boundaries and relationships have proved difficult to determine. Once thought to be a single species ranging across the eastern United States, protein analysis revealed high genetic divergences among geographically distinct groups of populations, leading to 16 species being recognized within the group. Two of these species, the Louisiana Slimy Salamander (Plethodon kisatchie) and the Mississippi Slimy Salamander (Plethodon mississippi), are closely related but occur on opposite sides of the Mississippi …

Genetic Counseling Student Self-Efficacy, Exam Anxiety, And Opinions Related To Study Materials For The Genetic Counseling Board Certification Exam., Jessica F. Stanton

USF Tampa Graduate Theses and Dissertations

The Genetic Counseling Board Examination is a critical assessment for clinical practice in the field. However, the relationship between students’ test-related anxiety, confidence in their ability to study (i.e., self-efficacy), and the use of gamification for board examination preparation remains unexplored. This study compared gamification and traditional quiz-style study methods using two randomized groups of students preparing for the Genetic Counseling Board Examination. The primary objectives were to assess for changes in exam-related anxiety and self-efficacy after completing the respective study materials and to evaluate the acceptability and completion rates of these materials. Ninety-eight genetic counseling students or recent graduates …

Agrobacterium-Mediated Genetic Transformation And Plant Regeneration From Cotyledons In Philippine Eggplant (Solanum Melongena L.) Acc. ‘Ph 11424’, Mark Gabriel Sagarbarria, John Albert Caraan, Patrick Lipio, Ian Bien Oloc-Oloc, Kazuo Watanabe, Desiree Hautea

The Philippine Agricultural Scientist

Eggplant (Solanum melongena L.) is one of the most important vegetables grown and consumed in the Philippines hence, continuous breeding programs are vital to maintain the supply of this economically important crop. This study demonstrates the first successful Agrobacterium-mediated genetic transformation and plant regeneration of the Philippine eggplant cultivar ‘PH 11424’, also known as ‘Mistisa’. Cotyledons from 2-wk-old seedlings were used as explants, which were transformed with disarmed Agrobacterium tumefaciens strain LBA4404 harboring a binary vector for CRISPR/Cas9 expression and hygromycin phosphotransferase (HPT), an antibiotic selection marker. Growth of shoot primordia from the agro-infected explants was observed during selective culture …

Educating Primary Care Providers On Use Of Pharmacogenetic Testing In Pain Management, Providence Sey

Walden Dissertations and Doctoral Studies

No abstract provided.

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Cold-Inducible Rna Binding Protein Impedes Breast Tumor Growth In The Pymt Murine Model For Breast Cancer, Daniel A. Lujan, Joey L. Ochoa, Ellen J. Beswick, Tamara A. Howard, Helen J. Hathaway, Nora I. Perrone-Bizzozero, Rebecca S. Hartley

Markey Cancer Center Faculty Publications

RNA binding proteins (RBPs) post-transcriptionally regulate gene expression by associating with regulatory sequences in the untranslated regions of mRNAs. Cold-inducible RBP (CIRP) is a stress-induced RBP that was recently shown to modulate inflammation in response to cellular stress, where it increases or decreases pro-tumorigenic (proinflammatory) cytokines in different contexts. CIRP expression is altered in several cancers, including breast cancer, but the effects of CIRP on inflammation in breast cancer is not known. Here, we investigate if CIRP alters growth and the inflammatory profile of breast tumors. Transgenic mice overexpressing CIRP in the mammary epithelium were crossed with the PyMT mouse …

Surveys Of Aphonopelma Hentzi In Missouri: Conservation Efforts Through Population, Genetics, And Habitat Studies, Anderson B. Spencer Mr., Becky Hansis-O'Niell

Undergraduate Research Symposium

Aphonopelma hentzi and other tarantula species are greatly understudied organisms. In the Missouri regions there is little knowledge on their mating patterns, gene diversity, or population sizes. The focal glades in this experiment display regional fragmentation, which could prevent tarantulas from traveling and mating between regions of their glades. Due to the lack of knowledge surrounding them, methods for determining gene diversity are harmful to the organism. Our recent work has shown that it is possible to extract genetic information from the molts of burrowing tarantulas. This will allow us to safely determine the lineages and interbreeding patterns of the …

Recovering Ancient Dna Using The Polymerase Chain Reaction, Rose Jennings

Undergraduate Research Symposium

Investigations into aDNA offer a window into the past that modern DNA and paleontological studies alone cannot provide and help address the evolution and connections between hominids, domestication timelines, the analysis of populations over time, and general diversity. Progress in aDNA research has been inherently technology-driven, with modern molecular biology methods, such as the inventions of Polymerase Chain Reaction (PCR) and Next Generation Sequencing (NGS), substantially increasing the analysis possibilities of aDNA. My research this semester has taken me along two parallel paths of investigation: literary research into aDNA and practical exposure to the laboratory techniques used in its analysis. …

Exploring The Evolution Of Callose Synthase In Green Plants, Giovanna Durante

The Journal of Purdue Undergraduate Research

No abstract provided.

Fusionnw, A Potential Clinical Impact Assessment Of Kinases In Pan-Cancer Fusion Gene Network, Chengyuan Yang, Himansu Kumar, Pora Kim

Faculty, Staff and Student Publications

Kinase fusion genes are the most active fusion gene group in human cancer fusion genes. To help choose the clinically significant kinase so that the cancer patients that have fusion genes can be better diagnosed, we need a metric to infer the assessment of kinases in pan-cancer fusion genes rather than relying on the sample frequency expressed fusion genes. Most of all, multiple studies assessed human kinases as the drug targets using multiple types of genomic and clinical information, but none used the kinase fusion genes in their study. The assessment studies of kinase without kinase fusion gene events can …

Delineating The Mechanism Of Fragility At Bcl6 Breakpoint Region Associated With Translocations In Diffuse Large B Cell Lymphoma, Vidya Gopalakrishnan, Urbi Roy, Shikha Srivastava, Khyati M Kariya, Shivangi Sharma, Saniya M Javedakar, Bibha Choudhary, Sathees C Raghavan

Faculty, Staff and Student Publications

BCL6 translocation is one of the most common chromosomal translocations in cancer and results in its enhanced expression in germinal center B cells. It involves the fusion of BCL6 with any of its twenty-six Ig and non-Ig translocation partners associated with diffuse large B cell lymphoma (DLBCL). Despite being discovered long back, the mechanism of BCL6 fragility is largely unknown. Analysis of the translocation breakpoints in 5' UTR of BCL6 reveals the clustering of most of the breakpoints around a region termed Cluster II. In silico analysis of the breakpoint cluster sequence identified sequence motifs that could potentially fold into …

Lipid Genetics In Pregnant Women: Maneuvering The Challenges Of Using Degraded Samples, Kylee Meece

Mahurin Honors College Capstone Experience/Thesis Projects

The results of this project will explore a novel approach to lipid metabolism in pregnant women by exploring the relationship between maternal gene expression of genes critical for fat metabolism, protein expression, and maternal and neonatal outcomes. The study will also examine gene expression in lean pregnant women compared to obese pregnant women, shedding light into the adverse pathology of obesity during pregnancy. These findings may uncover a mechanism related to gene-expression that connects unfavorable maternal fat metabolism to inflammation and/or insulin resistance, which may help to uncover future targets for interventions.

The analysis of lipid gene expression requires the …

Development Of A Novel Edna Sampling Method For Macroinvertebrate Species Of Greatest Conservation Need (Sgcn) In Texas, James York

Biology Theses

Environmental DNA (eDNA) sampling is a new sampling technique that allows for non-invasive sampling of target species or the characterization of entire communities based on barcoding genes. The goal of this study was to sequence common barcoding genes such as 28S rRNA and Cytochrome C Oxidase I (COI), and then develop species-specific primers for eight macroinvertebrates listed as Species of Greatest Conservation Need (SGCN) in Texas. After sampling for the target species, five were not found, all of which were in the Order Trichoptera (caddisflies). A sixth target species, Isoperla sagittata, was found to have only one gap and …

Precommentary: Animal Personality Needs Animal Sentience, Ralph Adolphs, Yue Xu

Animal Sentience

We are grateful to Owens, Bryja & Bekoff (2024) for their important discussion of individual differences in animals, emphasizing the role of personality in conservation, wildlife research, and wellbeing. But their emphasis also raises new challenges: How should we conceive of personality in nonhuman species? what modern tools could be leveraged to best measure it? and, perhaps most important of all: how can we ensure that the conscious experience of animals — their capacity for wellbeing and for suffering — is not forgotten along the way? We touch on each of these challenges in this invited Precommentary in the hope …

Individuality Matters But Its Cause Has Consequences, Daniel T. Blumstein

Animal Sentience

I discuss the relationship between individuality and heritability and note that the mechanism driving individual differences matters for conservation and management outcomes.

Understanding The Origin Of Parthenogenesis Via Crossing And Crispr Gene Editing In Daphnia Pulex, Thinh Pham

Biology Dissertations - Archive

Daphnia has been used as a key model system for studying ecological changes, evolution, and genomics for the past few decades due to its rapid turnover time in reproduction. The organism possesses two fascinating modes of reproduction: obligate parthenogenesis and cyclical parthenogenesis. This dissertation delves into the intricate reproductive strategies of Daphnia pulex, focusing on hybrid F1s from different reproductive modes. The first aim is to investigate 31 hybrid F1s generated from obligate parthenogenesis (OP) and cyclical parthenogenesis (CP) parental lines. Transcriptomic analysis reveals misexpression patterns and regulatory divergences, highlighting meiosis-related genes like CDC6 as potential parthenogenesis regulators. The …

Assessing The Utility Of Breast Cancer Polygenic Risk Scores And Association With Clinical Factors In A Population Of Breast Cancer Patients, John L. Slunecka

Dissertations and Theses

INTRODUCTION: Breast cancer (BC) is the most common cancer among women and is classified as a complex disease. Advances in population genomics have led to the development of polygenic risk scores (PRSs) with the potential to enhance current risk models, but replication is often limited. OBJECTIVE: We sought to assess the predictive capabilities of two high-powered BC PRSs in a sample population selected for breast cancer. In addition, the capacity of the PRSs to predict clinical variables that could improve BC screening and treatments was explored. METHODS: Two published PRS algorithms (313 vs 3820) were used to score female subjects …

The Effects Of Early Exposure To Prescription/Illicit Drugs And Drug Metabolites On Larval Zebrafish Behavioral And Motor Function Development, Jacob Thomas, Dena Weinberger, Bikram Subedi, Brandon Capps

Murray State Theses and Dissertations

THE EFFECTS OF EARLY EXPOSURE TO PRESCRIPTION/ILLICIT DRUGS AND DRUG METABOLITES ON LARVAL ZEBRAFISH BEHAVIORAL AND MOTOR FUNCTION DEVELOPMENT

A Thesis Presented to the Faculty of the Department of Biology

Murray State University

Murray, Kentucky

In Partial Fulfillment of the Requirements for the Degree of Masters In Science

By Jacob Thomas, B.S., Murray State University

December 2024

Acknowledgements

Brandon Capps, who pretty much did a whole third of the legwork on this project and saved me lots of headaches;

Chandler Maddox, one of the University of Kentucky’s finest undergrads who came in from the top rope with a folding chair …

The Role Of Liver-Specific Transcription Factor Hnf4 In Reprogramming Of Fibroblasts, Mary Odubote

Masters Theses

The mammalian liver, a vital organ with complex functions, relies on a network of transcription factors to regulate gene expression. Fusion of hepatoma cells with fibroblasts often leads to gene extinction, silencing approximately 400 liver-enriched genes, including critical transcription factors such as HNF4. Previous studies revealed that ectopic expression of HNF4 in fibroblasts failed to prevent the extinction of SERPINA1, a liver-specific gene, upon subsequent fusion with hepatoma cells. Here, we sought to investigate the extent to which ectopic expression of HNF4 can reprogram fibroblast cells and prevent gene extinction in hybrid cells.

Using whole-genome expression analysis, we compared RAT1 …

Plk1 Overexpression Drives Tumorigenesis In A Prostate Cancer Mouse Model, Emile Kachouh

Theses and Dissertations

Prostate cancer is the leading cause of cancer-related deaths among men worldwide, and the development of resistance to existing treatments necessitates the exploration of new therapeutic strategies, including combination therapies. This study investigates the role of Polo-like kinase 1 (PLK1), located on chromosome 16p12.2, as an oncogene in prostate cancer. We generated a transgenic mouse model with prostate-specific overexpression of PLK1 to closely mimic human prostate cancer progression. Quantitative PCR (qPCR) analysis was employed to characterize the molecular profile of PLK1, revealing its implication in multiple pathways. To further elucidate the functional consequences of PLK1 overexpression, we confirmed phenotypic progression …

The Splice Index As A Prognostic Biomarker Of Strength And Function In Myotonic Dystrophy Type 1, Marina Provenzano

Theses and Dissertations

Myotonic dystrophy type 1 (DM1) is a slowly progressive, multisystem disorder caused by a CTG repeat expansion in the DMPK 3’UTR that leads to global dysregulation of alternative splicing. The resulting decline in physical function is slow, and no reliable biomarkers exist for predicting disease progression; however, an RNA mis-splicing biomarker associated with weakness may have utility in predicting functional outcomes. Here we validate the Splice Index (SI) as a potential biomarker of DM1-associated strength and function. Muscle biopsies of the tibialis anterior were collected from DM1-affected individuals at baseline (n = 46) and 3-months (n = 34), along with …

Can Edna Be Used To Locate Shawnee Hills Cavefish Forbesichthys Papilliferus?, Megan Brandt, Timothy Spier Phd, Gary Zeruth Phd

Murray State Theses and Dissertations

Traditional stream fish sampling methods, such as seining and electrofishing, are time consuming, expensive, and limited to short stretches of stream. However, the analysis of environmental DNA (eDNA) from water samples promises to be a quick, inexpensive method for detecting fish. The streams of the Land Between the Lakes Recreational Area (LBL) are unique, undisturbed streams which contain many interesting fish species for which little information exists. One such rare species is the Shawnee Hills Cavefish Forbesichthys papilliferus, which is known to exist in a few LBL streams. However, the complete distribution of the Shawnee Hills Cavefish in LBL …

The Genetic Diversity Of An Endangered Buttercup, Ranunculus Triternatus, Ryan Garcia

All Graduate Projects

Ranunculus triternatus, a rare endemic species of the Columbia River Gorge, faces conservation challenges due to its limited range and fragmented populations. This study assesses the genetic diversity of R. triternatus and compares it with its widespread congener, Ranunculus glaberrimus, using inter-primer binding site (iPBS) markers. Genetic data from 80 individuals across eight populations were analyzed using Nei’s genetic diversity, Shannon’s diversity index, and AMOVA. Results showed R. triternatus had higher genetic diversity than western populations of R. glaberrimus, with eastern populations of R. glaberrimus displaying greater diversity than western ones. PCA, UPGMA, and STRUCTURE analysis revealed …

Delineating Contributions Of Genotype And Lineage To Lung Cancer Therapy Response, Kassandra Jo Naughton

Theses and Dissertations--Toxicology and Cancer Biology

Non-small cell lung cancer (NSCLC) heterogeneity is a major challenge for determining effective treatment strategies. Adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) are histologically and epigenetically distinct subtypes of NSCLC. Patients with ADC tumors harboring mutations in both KRAS and LKB1 (aka STK11) have lower survival rates than those with KRAS-only tumors. KRAS/LKB1 tumors are not only aggressive, but also respond poorly to immunotherapy. However, these data are limited to ADCs, and it is unclear if SCCs with this genotype are also resistant to immunotherapy. We developed a mouse model of Kras^mut/Lkb1^mut capable of producing …

Do Duckweeds Adapt To Water And Microbes?, Ava M. Rose

Honors Theses and Capstones

Organisms in their home environment sometimes outperform transplanted individuals native to other areas, in a phenomenon termed local adaptation. While local adaptation is traditionally considered to be driven by the abiotic factors of an environment, scientists have recently increased consideration of biotic factors. Specifically, of interest to many is host-associated microbiomes, which can alter host trait expression. As the desire to commercialize microbiome treatments for agriculture and medicine grows, it is important to analyze the potential value of local microbiomes, which may be adapted to their hosts, or to which local hosts may have adapted. Using Lemna minor (duckweed) as …

Investigating The Function Of Protein S-Acyltransferase 2 In Arabidopsis Thaliana Using Crispr Mutants, Nicole Benjamin

Honors Theses and Capstones

Arabidopsis thaliana contains 24 Protein Acyl Transferases (PATs). These enzymes are responsible for catalyzing the addition of a palmitate to a target substrate (palmitoylation). However, beyond its broad enzymatic function, it is unknown how PATs interact on a cellular level. This research focuses on identifying the function of PAT2. CRISPR-Cas9 was used to create deletion mutations that would result in a non-functional PAT. Two plants homozygous for a pat2 deletion were identified: pat2-5 and pat2-6. Preliminary results suggest that pollen grains in both pat2 mutants are larger in both length and width. Additionally, it appears that mutant pollen tends to …

Rare Variant Analyses Validate Known Als Genes In A Multi-Ethnic Population And Identifies Antxr2 As A Candidate In Pls, Tess D. Pottinger, Joshua E. Motelow, Gundula Povysil, Cristiane A. Martins Moreno, Zhong Ren, Hemali Phatnani, The New York Genome Center Als Sequencing Consortium, Timothy J. Aitman, Javier Santoyo‑Lopez, Scottish Genomes Partnership, Hiroshi Mitsumoto, Als Cosmos Study Group, Pls Cosmos Study Group, Gtac Investigators, David B. Goldstein, Matthew B. Harms

Neurology Faculty Publications

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people world‑ wide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible …

Functional Analyses Of The Polycomb-Group Genes In Sea Lamprey Embryos Undergoing Programmed Dna Loss, Cody Saraceno

Theses and Dissertations--Biology

During early embryonic development, the sea lamprey (Petromyzon marinus) undergoes programmatic elimination of DNA from somatic progenitor cells in a process termed programmed genome rearrangement (PGR). Eliminated DNA eventually becomes condensed into micronuclei, which are then physically degraded and permanently lost from the cell. Previous studies indicated that many of the genes eliminated during PGR have mammalian homologs that are bound by polycomb repressive complex (PRC) in embryonic stem cells. To test whether PRC components play a role in the faithful elimination of germline-specific sequences, we used a combination of CRISPR/Cas9 and lightsheet microscopy to investigate the impact …