Genetics and Genomics Commons^™

Nocturnal Foraging Enhanced By Enlarged Secondary Eyes In A Net-Casting Spider, Jay A. Stafstrom, Eileen A. Hebets

Eileen Hebets Publications

Animals that possess extreme sensory structures are predicted to have a related extreme behavioral function. This study focuses on one such extreme sensory structure—the posterior median eyes of the net-casting spider Deinopis spinosa. Although past research has implicated the importance of vision in the nocturnal foraging habits of Deinopis, no direct link between vision in the enlarged eyes and nocturnal foraging has yet been made. To directly test the hypothesis that the enlarged posterior median eyes facilitate visually based nocturnal prey capture, we conducted repeated-measures, visual occlusion trials in both natural and laboratory settings. Our results indicate that D. …

Rheb1 Expression In Embryonic And Postnatal Mouse, Qi Tian, James L. Smart, Joachim H. Clement, Yingming Wang, Alex Derkatch, Harald Schubert, Michael V. Danilchik, Daniel L. Marks, Lev M. Federov

Faculty Publications - Department of Biological & Molecular Science

Ras homolog enriched in brain (RHEB1) is a member within the superfamily of GTP-binding proteins encoded by the RAS oncogenes. RHEB1 is located at the crossroad of several important pathways including the insulin-signaling pathways and thus plays an important role in different physiological processes. To understand better the physiological relevance of RHEB1 protein, the expres-sion pattern of RHEB1 was analyzed in both embryonic (at E3.5–E16.5) and adult (1-month old) mice. RHEB1 immu-nostaining and X-gal staining were used for wild-type and Rheb1 gene trap mutant mice, respectively. These inde-pendent methods revealed similar RHEB1 expression pat-terns during both embryonic and postnatal developments. …

Congenic And Functional Analysis Of Rat Mammary Cancer Susceptibility., Saasha Le

Electronic Theses and Dissertations

Breast cancer is a complex disease affected by genetic, epigenetic and environmental factors. The genetic architecture of breast cancer comprises of high to low penetrance alleles. Although low penetrance alleles associate with a small change in an individual’s risk to breast cancer, the total number of variants present and the high population frequency attributes to a much greater population based impact compared to rare high penetrance alleles. Animal models have been used to study these low penetrance modifier alleles in breast cancer. Different rat strains vary in their susceptibility to 7,12- dimethybenzanthracene (DMBA) induced mammary carcinogenesis, with the Wistar- Furth …

Insights Into The Introduction Histories And Population Genetic Dynamics Of The Nile Monitor (Varanus Niloticus) And Argentine Black And White Tegu (Salvator Merianae) In Florida., Jared Price Wood

Electronic Theses and Dissertations

This dissertation examines the population genetic dynamics of two Florida invasives: the Nile monitor (Varanus niloticus) and Argentine black and white tegu (Salvator merianae). I also provide insights into the introduction histories of both species. This study was developed as part of a collaborative effort with the Florida Wildlife Commission to expand our knowledge of these highly detrimental, invasive lizards. All research activities involving animals and animal tissues were approved by the University of Louisville’s Institutional Animal Care and Use Committee (IACUC Proposal #: 12024). I start with a brief introduction into what makes invasive species …

Engineering A Mutation In The Heparin Binding Pocket Of The Human Fibroblast Growth Factor, Roshni Patel

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast growth factors (FGFs) are family of proteins that belong to a group of growth factors that are found in mammals and play an important role in angiogenesis, differentiation, organogenesis, and tissue repair. In summary, their main functionality is involved in cell division and proliferation. Because FGFs plays such a vital role in cell proliferation, they are mainly involved in the process of wound healing and injuries. FGF binds to its ligand, heparin—a heavily sulfated glycosaminoglycan. The binding of heparin to FGF occurs through electrostatic interactions, specifically between the negatively charged sulfate groups on heparin and positively charged residues such …

Integrity Of The Barrier Epithelium In Drosophila Gut Is Mediated By Factors That Regulate Intestinal Stem Cell Activity, Adam A. Kinion

Dissertations, Masters Theses, Capstones, and Culminating Projects

My thesis work on the Drosophila intestinal epithelium (IE) involved characterizing the mitochondrial unfolded protein response (UPRmt), validating proliferation specific regulatory genes, and proposing gut barrier function–specific genes as regulators of commensal bacteria density. The results from this project have shown that intestinal stem cells (ISCs) respond systemically in the presence of autonomously induced, visceral muscle (VM)-localized UPRmt. A phenotypic correlation between autonomous electron transport chain (ETC) dysfunction was observed in the visceral muscle and the systemic UPRmt response of ISCs in the posterior midgut. Exploratively, two genome-wide association studies (GWAS) using the Drosophila genetic reference panel (DGRP) were performed, …

Novel Interactome Of Saccharomyces Cerevisiae Myosin Type Ii Identified By A Modified Integrated Membrane Yeast Two-Hybrid (Imyth) Screen, Ednalise Santiago, Pearl Akamine, Jamie Snider, Victoria Wong, Matthew Jessulat, Viktor Deineko, Alla Gagarinova, Hiroyuki Aoki, Zoran Minic, Sadhna Phanse, Andrea San Antonio, Luis A Cubano, Brian C. Rymond, Mohan Babu, Igor Stagljar, Jose R. Rodriguez-Medina

Biology Faculty Publications

Nonmuscle myosin type II (Myo1p) is required for cytokinesis in the budding yeast Saccharomyces cerevisiae. Loss of Myo1p activity has been associated with growth abnormalities and enhanced sensitivity to osmotic stress, making it an appealing antifungal therapeutic target. The Myo1p tail-only domain was previously reported to have functional activity equivalent to the full-length Myo1p whereas the head-only domain did not. Since Myo1p tail-only constructs are biologically active, the tail domain must have additional functions beyond its previously described role in myosin dimerization or trimerization. The identification of new Myo1p-interacting proteins may shed light on the other …

Rhebi Expression In Embryonic And Postnatal Mouse, Qi Tian, James L. Smart, Joachim H. Clement, Yingming Wang, Alex Derkatch, Harald Schubert, Michael V. Danilchik, Daniel L. Marks, Lev M. Fedorov

Faculty Publications - Department of Biological & Molecular Science

Ras homolog enriched in brain (RHEB1) is a member within the superfamily of GTP-binding proteins encoded by the RAS oncogenes. RHEB1 is located at the crossroad of several important pathways including the insulin-signaling pathways and thus plays an important role in different physiological processes. To understand better the physiological relevance of RHEB1 protein, the expres- sion pattern of RHEB1 was analyzed in both embryonic (at E3.5–E16.5) and adult (1-month old) mice. RHEB1 immu- nostaining and X-gal staining were used for wild-type and Rheb1 gene trap mutant mice, respectively. These inde- pendent methods revealed similar RHEB1 expression pat- terns during both …

The Uas-Gal4 System In D. Melanogaster: An Insight Into The Influence Of Micrornas On The Developmental Pathways Of The Wing, Emily R. Wilson

Honors Theses

By examining genetic pathways in D. melanogaster, a better understanding of the homologous regulatory mechanisms in humans can be utilized to further enhance knowledge of the roles of microRNA within development. This study utilizes the UAS-Gal4 system in order to produce a mutant phenotype capable of being visually studied and analyzed, focusing on the developmental pathway of the wing in D. melanogaster. Dissections of the wandering third instar larvae yielded wing disc tissue expressing the downregulation of loquacious and CG17386.

Alzheimer's Disease: The Silver Tsunami Of The 21st Century, Ankita Sarkar, Madison Irwin, Aditi Singh, Matthew Riccetti, Amit Singh

Biology Faculty Publications

Alzheimer's disease (AD), a fatal progressive neurodegenerative disorder, has no cure to date. One of the causes of AD is the accumulation of amyloid-beta 42 (Aß42) plaques, which result in the onset of neurodegeneration. It is not known how these plaques trigger the onset of neurodegeneration. There are several animal models developed to (i) study etiology of disease, (ii) look for genetic modifiers, and (iii) identify chemical inhibitors that can block neurodegeneration and help to find cure for this disease. An insect model of Drosophila melanogaster has also provided new insights into the disease. Here we will discuss the utility …

Ethnic Identity And Teratogenic Risk Perceptions, Katie M. Chan

Dissertations and Theses (Open Access)

Elevated perceptions of teratogenic risk can cause anxiety and confusion among pregnant women. To assess whether ethnic identity and demographic factors can influence teratogenic risk perceptions, 194 pregnant women in Houston were surveyed using the Multigroup Ethnic Identity Measure (MEIM) and visual analog scales to quantify perceptions of teratogenic risk for common exposures during pregnancy. Overall, participants estimated an elevated baseline risk of 25% for birth defects among the general population. In addition, participants overestimated birth defect risks for specific exposures, such as alcohol and marijuana. Based on the MEIM scores, ethnic identity was not significantly associated with teratogenic risk …

The Effect Of Transformed Escherichia Coli On The Mouse Intestine Microbiome: The Microbial Metabolic Enhancement Hypothesis, Bryar P. Kader

Senior Honors Theses

Metabolic disorders affect around thirty-four percent of the population in the United States. Among these disorders is lactose intolerance, which results from diminished production of the human lactase enzyme. This disorder and others like it are genetically determined and cannot be cured. However, the use of transformed bacteria implanted in the colon may provide a means by which the faulty pathway can be bypassed. To test whether transformed bacteria have the capability to aid in the digestion of normally indigestible compounds, a transformed strain of Escherichia coli overexpressing the beta-galactosidase enzyme encoded by the lacZ gene was colonized in the …

Identification Of Biomarkers For The Overall Survival Of Ovarian Cancer Patients, Kristi Mai

Graduate Theses and Dissertations

Rapid advance in sequencing technology has led to genome-wide analysis of genetic and epigenetic features simultaneously, making it possible to understand the biological mechanisms underlying cancer initiation and progression. However, how to identify important prognostic features poses a great challenge for both statistical modeling and computing. In this thesis, a network-based approach is applied to the Cancer Genome Atlas (TCGA) ovarian cancer data to identify important genes related to the overall survival of ovarian cancer patients. In the first step, a stepwise correlation-based selector is used to reduce the dimensionality of TCGA data, by filtering out a large number of …

Ecology And Genetics Of Lungless Salamanders (Family Plethodontidae) In The Gulf Coastal Plain, Jennifer Yasmin Lamb

Dissertations

During the last half century, lungless salamanders (Family Plethodontidae) have been the subject of numerous studies in the fields of ecology and genetics. While most works have focused on the species-rich Eastern Highlands region, there has been a recent shift towards plethodontid assemblages within the Coastal Plain. The research presented herein applies hierarchical occupancy models and both mitochondrial and nuclear genes to address questions pertinent to the biology and conservation of plethodontids within the Gulf Coastal Plain. The results of a multi-species Bayesian single-season occupancy model indicated that two environmental gradients, upstream drainage area and stream drying, influenced the probability …

Performance Benchmarks For Scholarly Metrics Associated With Fisheries And Wildlife Faculty, Robert K. Swihart, Mekala Sundaram, Tomas O. Höök, James Andrew Dewoody, Kenneth F. Kellner

Department of Forestry & Natural Resources Faculty Publications

Research productivity and impact are often considered in professional evaluations of academics, and performance metrics based on publications and citations increasingly are used in such evaluations. To promote evidence-based and informed use of these metrics, we collected publication and citation data for 437 tenure-track faculty members at 33 research-extensive universities in the United States belonging to the National Association of University Fisheries and Wildlife Programs. For each faculty member, we computed 8 commonly used performance metrics based on numbers of publications and citations, and recorded covariates including academic age (time since Ph.D.), sex, percentage of appointment devoted to research, and …

Molecular Evolutionary Analysis Of The American Pika (Ochotona Princeps), Andrew Michael Rankin

All NMU Master's Theses

American pika (Ochotona princeps) are small winter-active mammals inhabiting alpine environments. As the American pika occupies a niche characterized by hypoxia, these animals are an excellent system to use for detecting genetic changes associated with adaptation to these conditions. American pika populations were located at lower elevations during glacials, and shifted upslope during interglacials. In this scenario, pikas would have experienced increased selective pressure to develop adaptations to hypoxia. Here, I use a candidate gene approach to identify molecular signals of adaptation in the American pika genome. I first examined the sequences of 54 candidate genes for adaptation …

Characterization Of Induced Rnai Silencing Of Vaccinia Virus Essential Genes, Kewa Jiang

Honors Scholar Theses

Vaccinia virus (VACV) is a large double-stranded DNA virus and the prototypical member of the family Poxviridae and is most notable for its use as the vaccine that eradicated smallpox (variola virus). More recently, VACV has been used to develop recombinant vaccines and immunotherapies. However, many of these processes require VACV replication to be tightly controlled. RNA interference (RNAi) is a powerful tool for in vitro silencing of mRNAs that are complementary to 19-21 base pairs (bp) of double-stranded RNA (dsRNA). This project outlines the design and preliminary analysis of two inducible RNAi silencing constructs targeting multiple VACV essential genes …

Genomic Drivers Of Cutaneous Squamous Cell Carcinoma Development, Vida Chitsazzadeh

Dissertations and Theses (Open Access)

Skin cancer is the most common malignancy in humans. Annually, in U.S. there are over 3 million cases with an estimated overall economic impact of $2 billion. Cutaneous Squamous Cell Carcinoma (cuSCC) comprises 15-20% of all skin cancers. cuSCC has the best-defined progression from a distinct precancerous lesion, the Actinic Keratosis (AK), to invasive cuSCC. Destructive therapies for AK treatment must be used repetitively, causing significant morbidity. There is a tremendous need for targeted diagnostics and therapy for AKs, representing an important opportunity for secondary skin cancer prevention. Our knowledge of the molecular and cellular events that lead to the …

The Thioredoxin Trx-1 Regulates The Major Oxidative Stress Response Transcription Factor, Skn-1, In Caenorhabditis Elegans, Katie C. Mccallum

Dissertations and Theses (Open Access)

The ability to respond to hostile environmental conditions is critical for the survival of an organism. Oxidative stress is an adverse state in which reactive oxygen species (ROS) accumulate to a harmful level and, if left unresolved, can lead to cellular dysfunction and organismal disease. Sophisticated detoxification systems, characterized by a battery of enzymatic antioxidants, are utilized to neutralize ROS thereby reducing stress. However, ROS are also purposefully produced by designated cellular enzymes to facilitate the signaling and regulation of critical physiological processes. Therefore, both the production and neutralization of ROS must be tightly controlled. Indeed, the expression of detoxification …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations and Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Investigating Metastatic Lineage In Colorectal Cancer By Single Cell Dna Sequencing, Marco Leung

Dissertations and Theses (Open Access)

Metastasis is the primary cause of human cancer deaths. Patients with metastatic colorectal cancer (mCRC) show only an 11% 5-year survival rate, compared to those without local or distant metastases (92% 5-year survival rate). Understanding the CRC tumor evolution may provide valuable insights on how to improve treatment in patients with mCRC. However, the genomic basis of metastasis has been difficult to study, in part due to the extensive intratumor heterogeneity at both the primary and metastatic tumor sites, and the low frequency of subclones with metastatic potential. Previous studies have applied conventional bulk next-generation sequencing (NGS) methods, which have …

Accurate Mutation Annotation And Functional Prediction Enhance The Applicability Of -Omics Data In Precision Medicine, Tenghui Chen

Dissertations and Theses (Open Access)

Clinical sequencing has been recognized as an effective approach for enhancing the accuracy and efficiency of cancer patient management and therefore achieve the goals of personalized therapy. However, the accuracy of large scale sequencing data in clinics has been constrained by many different aspects, such as clinical detection, annotation and interpretation of the variants that are observed in clinical sequencing data. In my Ph.D thesis work, I mainly investigated how to comprehensively and efficiently apply high dimensional -omics data to enhance the capability of precision cancer medicine. Following this motivation, my dissertation has been focused on two important topics in …

Nipt Results Indicative Of Maternal Neoplasms: Genetic Counselors' Preferences And Attitudes, Meagan E. Giles

Dissertations and Theses (Open Access)

Performing non-invasive prenatal testing (NIPT) on a pregnant woman with a chromosomally abnormal neoplasm may incidentally lead to the diagnosis of cancer due to the coexistence of circulating tumor and placental DNA. Published information regarding NIPT’s accuracy for neoplasm screening is limited, and guidance for patient management is currently lacking. This challenges clinicians’ ability to counsel patients regarding the implications of these results, which often is the responsibility of a genetic counselor. Over three hundred board-eligible/certified genetic counselors were surveyed regarding their awareness, preferences, and attitudes towards NIPT’s ability to indicate maternal neoplasms. Despite 95% of this cohort being aware …

The Role Of Cellulose Synthase-Like D Genes In Tip Growth Of Physcomitrella Patens, Erin E. Killeavy, Arielle Chaves, Alison Roberts

Senior Honors Projects

Physcomitrella patens is a non-vascular plant with a relatively small genome and is amongst the few eukaryotic organisms that have a high rate of homologous recombination. This is valuable in biological research because it allows for targeted genetic modification of the organism. In vascular plants like Arabidopsis thaliana, a model organism, Cellulose Synthase-like D (CSLD) genes have been discovered to be important in tip growth. This type of growth is observed in the pollen tubes and root hairs of these plant types. The CSLD genes in Arabidopsis were found to play a crucial role in the growth of …

General Approach For Combining Diverse Rare Variant Association Tests Provides Improved Robustness Across A Wider Range Of Genetic Architectures, Brian Greco, Allison Hainline, Jaron Arbet, Kelsey Grinde, Alejandra Benitez, Nathan L. Tintle

Faculty Work Comprehensive List

The widespread availability of genome sequencing data made possible by way of next-generation technologies has yielded a flood of different gene-based rare variant association tests. Most of these tests have been published because they have superior power for particular genetic architectures. However, for applied researchers it is challenging to know which test to choose in practice when little is known a priori about genetic architecture. Recently, tests have been proposed which combine two particular individual tests (one burden and one variance components) to minimize power loss while improving robustness to a wider range of genetic architectures. In our analysis we …

Hybridization, Population Genetic Structure And Gene Expression In The Genus Boechera, Martin Peter Schilling

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

When we look at life on earth, we can see a lot of different life forms, but we still do not fully understand how these different life forms came to be and at which points in time these life forms began to be different enough from each other so we could call them by different names, or species. Some groups of species on earth, especially plants, seem to reproduce with each other, even though they are already very different from each other so that we call them different species. This process is called hybridization, and it can stir up the …

Opsin Repertoire And Expression Patterns In Horseshoe Crabs: Evidence From The Genome Of Limulus Polyphemus (Arthropoda: Chelicerata), Barbara-Anne Battelle, Joseph F. Ryan, Karen E. Kempler, Spencer R. Saraf, Catherine E. Marten, Wesley C. Warren, Patrick J. Minx, Michael J. Montague, Pamela J. Green, Skye A. Schmidt, Lucinda Fulton, Nipam H. Patel, Meredith E. Protas, Richard K. Wilson, Megan L. Porter

Collected Faculty Scholarship

Horseshoe crabs are xiphosuran chelicerates, the sister groupto arachnids. As such, they are important for understandingthemost recent common ancestor of Euchelicerata and the evolution and diversification of Arthropoda. Limulus polyphemus is the most investigated of the four extant species of horseshoe crabs, and the structure and function of its visual system have long been a major focus of studies critical for understanding the evolution of visual systems in arthropods. Likewise, studies of genes encoding Limulus opsins, the protein component of the visual pigments, are critical for understanding opsin evolution and diversification among chelicerates, where knowledge of opsins is limited, and …

Nuclear Architecture And Patterns Of Molecular Evolution Are Correlated In The Ciliate Chilodonella Uncinata, Xyrus X. X. Maurer-Alcala, Laura A. Katz

Biological Sciences: Faculty Publications

The relationship between nuclear architecture and patterns of molecular evolution in lineages across the eukaryotic tree of life is not well understood, partly because molecular evolution is traditionally explored as changes in base pairs along a linear sequence without considering the context of nuclear position of chromosomes. The ciliate Chilodonella uncinata is an ideal system to address the relationship between nuclear architecture and patterns of molecular evolution as the somatic macronucleus of this ciliate is composed of a peripheral DNA-rich area (orthomere) and a DNA-poor central region (paramere) to form a “heteromeric” macronucleus. Moreover, because the somatic chromosomes of C. …

Epigenetic Profiles Signify Cell Fate Plasticity In Unipotent Spermatogonial Stem And Progenitor Cells, Ying Liu, Eugenia G. Giannopoulou, Duacheng Wen, Ilaria Falciatori, Oliver Elemento, C. David Allis, Shahin Rafii, Marco Seandel

Publications and Research

Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin. At enhancers, the core pluripotency circuitry is activated partially in SSCs and completely in MASCs, concomitant with loss of …

Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray

Pharmacology and Nutritional Sciences Faculty Publications

Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.

Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using …