Digital Commons Network^™

Niche Modeling Of Eight Crayfish Species In Texas, Nathan Schubert

Biology Theses

Freshwater species make up ~10% of all known species and occupy less than one percent of earth’s habitat, which is being degraded by human usage. Crayfish have a large impact on their aquatic or terrestrial environment and can serve as a health indicator of aquatic environments, as they generally require undegraded environments. In many habitats, crayfish make up more than half of the macroinvertebrate biomass, and play important ecological roles, as a food resource for both aquatic and terrestrial species, as predators of fish and invertebrates, and as bioprocessors of vegetation and detritus. The objective of this project was to …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

Impact Of Covid-19 On A Worksite Weight Loss Program For Employees With Overweight And Obesity, Che Young Lee, Michael C Robertson, Kendahl Servino, Thuan Le, Margaret Raber, Katherine Oestman, Karen M Basen-Engquist

Faculty, Staff and Students Publications

OBJECTIVE: The COVID-19 pandemic has been shown to be negatively associated with physical activity engagement, adherence to healthy diet, and weight management among people with obesity. The current study examined COVID-19-related changes in weight, physical activity (PA), and diet among employees with obesity or overweight who participated in Vibrant Lives (VL), a worksite weight loss program.

METHODS: School district employees participated in the 6-month VL weight loss program and were categorized into non-COVID-era participants and COVID-era participants. Participants completed questionnaires about PA and dietary intake at baseline and follow-up. COVID-era participants reported the effects of pandemic on their behaviors. Changes …

Systemic Delivery Of Divalent Europium From Ligand Screening With Implications To Direct Imaging Of Hypoxia, Md Mamunur Rashid, Brooke A Corbin, Pavan Jella, Caitlyn J Ortiz, Md Abul Hassan Samee, Robia G Pautler, Matthew J Allen

Faculty, Staff and Students Publications

Hypoxia is a hallmark of many diseases, including cancer, arthritis, heart and kidney diseases, and diabetes, and it is often associated with disease aggressiveness and poor prognosis. Consequently, there is a critical need for imaging hypoxia in a noninvasive and direct way to diagnose, stage, and monitor the treatment and development of new therapies for these diseases. Eu-containing contrast agents for magnetic resonance imaging have demonstrated potential for in vivo imaging of hypoxia via changes in metal oxidation state from +2 to +3, but rapid oxidation in blood limits EuII-containing complexes to only studies compatible with direct injection to sites. …

Thermal Tolerance And Physiology Of Eleutherodactylus Coqui Along An Elevational Gradient In Hawai‘I, Karen H. Beard, Susannah S. French, Jack Marchetti

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The purpose of this study was to determine if the thermal tolerance and physiology of the coqui frog changed along HawaiÔiÕs elevation gradient. A short acclimation experiment was used to test the baseline thermal tolerance and physiology, and an extended acclimation experiment to test the acclimation ability of the thermal tolerance and physiology metrics of the coqui frogs collected from low (m), medium (350-550 m) and high elevations (>750 m).

Droughts Reduce Growth Rates And Increase Vulnerability To Increasingly Frequent And Severe Drying Events In An Aquatic Ectotherm, Thomas M. Luhring, Lyndsie S. Wszola, Grant M. Connette, Christopher M. Schalk

School of Biological Sciences: Faculty Publications

Many aquatic organisms are experiencing increasingly severe and frequent droughts and drying events. Simultaneously, drought effects are carrying over to non-drought years as ecosystems remain in incomplete states of recovery. Aquatic organisms are thus faced with fewer sequential years under degraded environmental conditions to prepare for increasingly severe droughts and potential drying events. We assessed the effect of droughts and sex on the growth, mass, and mass-dependent estivation potential of long-lived aquatic salamanders (Greater Sirens, Siren lacertina) that estivate during drying events brought on by severe droughts. We calculated growth rates of S. lacertina based on mark–recapture data spanning …

Antibody Epitope Profiling Of The Kshv Lana Protein Using Virscan, Sydney J. Bennett, Dicle Yalcin, Sara R. Privatt, Owen Ngalamika, Salum J. Lidenge, John T. West, Charles Wood

School of Biological Sciences: Faculty Publications

The humoral antibody response against Kaposi sarcoma-associated herpesvirus (KSHV) in infected individuals has been characterized demonstrating the latency-associated nuclear antigen (LANA) as the most antigenic KSHV protein. Despite the antigenicity of the protein, specific LANA epitopes have not been systematically characterized. Here, we utilized a bacteriophage T7 library, which displays 56-amino acid KSHV LANA peptides with 28-amino acid overlap (VirScan), to define those epitopes in LANA targeted by antibodies from a cohort of 62 sub-Saharan African Kaposi sarcoma (KS) patients and 22 KSHV-infected asymptomatic controls. Intra- and inter-patient breadth and magnitude of the anti-LANA responses were quantified at the peptide …

Droughts Reduce Growth Rates And Increase Vulnerability To Increasingly Frequent And Severe Drying Events In An Aquatic Ectotherm, Thomas M. Luhring, Lyndsie S. Wszola, Grant M. Connette, Christopher M. Schalk

School of Biological Sciences: Faculty Publications

Many aquatic organisms are experiencing increasingly severe and frequent droughts and drying events. Simultaneously, drought effects are carrying over to nondrought years as ecosystems remain in incomplete states of recovery. Aquatic organisms are thus faced with fewer sequential years under degraded environmental conditions to prepare for increasingly severe droughts and potential drying events. We assessed the effect of droughts and sex on the growth, mass, and mass-dependent estivation potential of long-lived aquatic salamanders (Greater Sirens, Siren lacertina) that estivate during drying events brought on by severe droughts. We calculated growth rates of S. lacertina based on mark–recapture data spanning …

Roles Of Individual Protein In De Novo Polycomb Protein Recruitment, Piao Ye

Biological Sciences Theses and Dissertations

Polycomb Group (PcG) proteins are evolutionarily conserved epigenetic transcriptional regulators that maintain the transcriptional repression of silenced genes by maintaining heritable chromatin states. PcG proteins first discovered as repressors of Hox genes in Drosophila, later were shown to regulate a wide range of genes. In mammals, PcG proteins are involved in maintaining pluripotent state of stem cells and controlling cell differentiation. Misexpression of PcG protein leads to cancers like lymphoma and melanoma. PcG proteins maintain rather than initiate transcriptional repression, once PcG – mediated repression is established it can be maintained through an unlimited number of cycles. Most studies of …

Elevation Influences The Microhabitat Use And Baseline Physiology Of Coqui Frogs In Hawai‘I, Karen H. Beard, Susannah S. French, Jack Marchetti

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The purpose of this study was to determine whether elevation in HawaiÔi affects the coquiÕs microhabitat use such as substrate choice and height off the forest floor and physiological metrics such as osmolality, oxidative status, and energy metabolites (glucose, free glycerol, and triglycerides).

Benthic Macroinvertebrate Pre-Assessment Of A Proposed Restoration In The Grand River, Grand Rapids, Mi, Usa, Matthew L. Bain

Masters Theses

River restoration is the dominant field of applied water resources management in the United States. Ecological improvement should be the goal of all river restorations, though many restoration projects fail to produce positive results due to limited scope or inadequate assessment methodologies. Pre-restoration, biotic data is essential for such projects as it can be paired with post-restoration data to gauge ecological outcomes. A major restoration effort is now underway in Michigan's longest river, the Grand River, where it flows through downtown Grand Rapids. The primary restoration measures will occur in-stream at local scale. We conducted a pre- restoration survey for …

Relationships Among Age, Relative Telomere Length, And Dna Methylation In Pteropus Bats, Erika E. Forest

Masters Theses

Bats are the longest-lived mammalian order relative to body mass, but questions remain about relationships among mechanisms related to aging. Relative telomere length (rTL) decreases with age in most mammals, but the relationship between age and rTL is highly variable among the few bat taxa studied to date. More recently, DNA methylation (DNAm), a type of epigenetic regulation in which methyl groups are added to cytosine-phosphate-guanine (CpG) sites across the genome, has been shown to be highly predictive of age in many species of bats. We examine the relationships among age, rTL, and DNAm in Pteropus pumilus and P. hypomelanus …

Optimized Production Of Second-Generation Bioethanol From A Spent C4 Grass: Vetiver (Chrysopogon Zizanioides), Sameer Neve, Dibyendu Sarkar, Zhiming Zhang, Rupali Datta

Michigan Tech Publications, Part 1

Vetiver grass (Chrysopogon zizanioides) is well-known for its contaminant phytoextraction potential and its capacity to reduce soil erosion, owing to its massive, dense root system. However, the shoots are not major contributors to either of these processes, and are either not utilized at all or they become part of the waste stream. It is well-recognized that lignocellulosic biomass can serve as a source of raw material to produce second-generation bioethanol. This study investigated the simultaneous saccharification and fermentation (SSF) of acid–alkali pretreated vetiver (VG) shoots by Saccharomyces cerevisiae. Vetiver shoots were obtained from three sources: (1) shoots from VG grown …

The Y-Chromosome's Role In Sexually Dimorphic Evolution And Mother's Curse Compensation, Tobias Nielsen

Electronic Theses and Dissertations, 2020-2023

The Y-chromosome and mitochondria (containing mtDNA) appear entirely dissimilar, the former being a sex chromosome found in the nucleus and the latter an organelle with thousands of copies in the cytoplasm. However, both experience uniparental inheritance, with Y-chromosomes being patrilineal and mitochondria matrilineal. This leads to various other similarities including haploidy, high mutation rates, and limited or lack of genetic recombination. Moreover, the low number of protein-coding genes contained on both led to the belief that neither contributes significantly to the adaptive evolution of complex traits. However, recent studies show the Y-chromosome and mitochondria both influence roughly 10% of male …

An Amino-Terminal Fragment Of Apolipoprotein E4 Leads To Behavioral Deficits, Increased Phf-1 Immunoreactivity, And Mortality In Zebrafish, Madyson M. Mccarthy, Makenna J. Hardy, Saylor E. Leising, Alex M. Lafollette, Erica S. Stewart, Amelia S. Cogan, Tanya Sanghal, Katie Matteo, Jonathon C. Reeck, Julia T. Oxford, Troy T. Rohn

Biology Faculty Publications and Presentations

Although the increased risk of developing sporadic Alzheimer’s disease (AD) associated with the inheritance of the apolipoprotein E4 (APOE4) allele is well characterized, the molecular underpinnings of how ApoE4 imparts risk remains unknown. Enhanced proteolysis of the ApoE4 protein with a toxic-gain of function has been suggested and a 17 kDa amino-terminal ApoE4 fragment (nApoE4_1-151) has been identified in post-mortem human AD frontal cortex sections. Recently, we demonstrated in vitro, exogenous treatment of nApoE4_1-151 in BV2 microglial cells leads to uptake, trafficking to the nucleus and increased expression of genes associated with cell toxicity …

System Shock: Using -Omics Data To Characterize Biological Remodeling In The Microbiome, Resistome, And Transcriptome Of Bacteria, Winston Eugene Anthony

Arts & Sciences Graduate Student Theses and Dissertations

The human experience is indelibly linked to microbial life. So much so, that the holobiont theory has been coined to define the assemblage of host and microbe as a discrete ecological unit. Perturbation of the commensal microbiome can create niche space for pathogens, which through the concomitant rise of antimicrobial resistance represent an ever-evolving danger. In Chapter 2 of this dissertation, I describe the results of an interventional study designed to directly perturb the healthy gut microbiome and observe the dynamics of taxonomic composition and functional recovery. I observe significant decreases after 5 days of antibiotic treatment in the gold …

Circadian Circuitry And Glioblastoma: Interactions With Behavior, Carcinogenesis, And Clinical Practice., Anna R. Damato

Arts & Sciences Graduate Student Theses and Dissertations

Glioblastoma (GBM) is the most common primary adult brain tumor diagnosed, with a 15-month prognosis using current standard of care treatment which includes chemotherapy with temozolomide (Temodar, TMZ). Chronotherapy, the practice of considering time of day in treating a disease, has been shown to improve outcome in several cancers, but had not been applied to GBM. Previous work in the lab on a cultured murine mesenchymal GBM cell line showed a time-of-day dependent maximum in sensitivity to TMZ corresponding with the daily peak of Bmal1 and trough of Per2 expression, two core clock genes. Based on this finding, we sought …

Cooperation And Conflict In The Social Amoeba Dictyostelium Discoideum And Its Paraburkholderia Endosymbionts, James Medina

Arts & Sciences Graduate Student Theses and Dissertations

A big question in biology is how organisms compete in an environment of competitors for scarce resources. Part of the answer lies in distinguishing friend from foe and in forging cooperative bonds in the face of cheaters. The social amoeba – bacteria system I have studied here is an excellent place to explore these tensions. The first part of my thesis research involves a review of cooperation and conflict in the social amoeba Dictyostelium discoideum and a study of the limits on obligate social cheating in this species. The second part focuses on the benefits of associating with D. discoideum …

The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland

Arts & Sciences Graduate Student Theses and Dissertations

The N-methyl-D-aspartate receptor (NMDAR) plays a variety of important roles in the development and function of primate central nervous systems. This thesis describes three nonhuman primate studies that, together, demonstrate that pharmacologically reducing NMDAR activity not only causes dramatic changes in neural activity in cortex, but also changes the relationship between that activity and a key signal often used as its proxy in human studies, the blood-oxygen-level-dependent (BOLD) signal. The first study reveals that NMDA antagonism is sufficient to induce powerful low-frequency modulation of spiking activity and extracellular local field potential (LFP) and discusses the implications of this finding for …

Analysis Of Regulatory Element Variation In Autism Spectrum Disorder, Evin Mitchel Padhi

Arts & Sciences Graduate Student Theses and Dissertations

Autism Spectrum Disorder (ASD) is a highly prevalent neurodevelopmental disorder that affects over 2% of the population. Studies of this disorder have demonstrated that genetics plays a strong role in the underlying etiology and over the past decade, substantial progress has been made in elucidating the genetic architecture. Large-scale studies have now been conducted to identify the genes involved in the genetic architecture by analyzing data from over 40,000 probands. However, the identification and characterization of regulatory elements involved have remained non-trivial for many reasons. Generally, studies that have analyzed whole genome sequencing (WGS) have demonstrated enrichment of de novo …

The Impact Of Nucleolar Stress On Thymocyte Development And T Cell Acute Lymphoblastic Leukemia Transformation, Joseph Ryan Krambs

Arts & Sciences Graduate Student Theses and Dissertations

Increased Notch signaling is thought to be central to T-ALL pathogenesis, with activatingmutations of NOTCH1 in 60% of cases, and Notch pathway activation due to mutations in FBXW7 in an additional 15% of cases. Increased Notch signaling results in markedly increased ribosome biogenesis, inducing a negative feedback loop called the nucleolar stress pathway. This is an evolutionarily conserved homeostatic pathway that is triggered by excessive ribosome biogenesis that serves to limit rRNA synthesis, protein translation, and ultimately cell growth. CDKN2A, encoding both ARF and INK4A, plays a key role in the nucleolar stress pathway. Activation of ARF and INK4A inhibits …

Inferring Adaptation In Social Microbes From Experimental Evolution Under Relaxed Selection, Tyler John Larsen

Arts & Sciences Graduate Student Theses and Dissertations

Microbes exist against a backdrop of other organisms, and the interactions between microbes have major consequences on their traits, their evolution, and their impact on the world. Microbial interactions and the adaptations that enable them are extremely diverse – they can unlock abilities beyond the reach of individual cells or lead to a population’s destruction, they can be temporary or permanent, they can be between genetically identical cells or different species entirely. The first chapter of this dissertation reviews microbial interactions and the related concept of the evolution of conflict and cooperation.To be certain a trait is an adaptation at …

Single-Cell Massively Parallel Reporter Assays, Siqi Zhao

Arts & Sciences Graduate Student Theses and Dissertations

Our understanding of gene regulation needs to be generalizable as well as specific. A generalizable understanding enables us to transfer our knowledge of one gene to another, and the specificity allows us to understand the precise regulation of gene expression through development. One framework that confers generalizability and specificity is the hierarchical and modular model of gene regulation. To test whether gene regulation is hierarchical and modular requires methods to systematically analyze how different factors collectively control gene expression. This thesis describes the development of two functional genomics methods at single-cell resolution. These methods systematically examined how cellular contexts, chromatin …

Host Development And Microbiota Influences On Norovirus Infection, Elizabeth Alexandra Kennedy

Arts & Sciences Graduate Student Theses and Dissertations

The mammalian gut is a complex organ which changes over the course of development and is influenced by the presence of a dense community of gut-resident microbes. Enteric viruses infect the gastrointestinal tract in the context of the commensal microbiota and host immunity. Here, we dissect the influence of host developmental stage and the gut microbiota in norovirus infection. From this work, we determine that murine norovirus (MNoV) infection in early life is restricted by an absence of the target MNoV cell tuft cells and intact interferon (IFN) signaling. However, viral inoculum taken up by non-specific endocytosis in the neonatal …

Bioinformatics And Cancer Genomics Approaches To Advance Precision Medicine And Elucidate Tumor Mutational Landscapes, Kelsy Cotto

Arts & Sciences Graduate Student Theses and Dissertations

Next-generation sequencing of DNA and RNA continues to be integrated into pre-clinical and clinical research. However, challenges still remain that impede the translation of findings into an improved understanding of human diseases or clinically actionable alterations. The projects described in this dissertation start with compiling efforts from experts who have identified druggable genes within the human genome, followed by in-depth analyses which characterize the pan-cancer landscape of splice-associated mutations and noncoding, regulatory mutations across multiple subtypes of breast cancer. In Chapters 2 and 3, substantial efforts were made to update the content and the user experience for the drug-gene interaction …

Insights Into The Non-Osmoregulatory Function Of A Pollen-Specific Mechanosensitive Ion Channel, Kari Miller

Arts & Sciences Graduate Student Theses and Dissertations

Pollen, the male gametophyte of flowering plants, delivers the sperm cells to the ovule to carry out sexual reproduction. During this process, the pollen grain undergoes dramatic physical changes. Survival requires careful control of cell mechanics, particularly the balance between protoplast expansion and cell wall resistance. One control mechanism is the use of a mechanosensitive (MS) ion channel, MscS-Like (MSL)8. This pollen-specific protein was previously shown to be essential for pollen survival during hydration and was proposed to function as a tension-gated osmoregulator. However, direct proof of osmoregulation during initial hydration has not yet been found. In fact, studies of …

The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan

Arts & Sciences Graduate Student Theses and Dissertations

The circadian clock and inflammation have a well-described bidirectional relationship in the peripheral immune system: the circadian clock regulates inflammatory responses, but inflammation also impacts oscillatory gene transcription controlled by the clock. The purpose of this thesis work is to understand if manipulation of the circadian clock can impact Alzheimer’s disease pathology, and if pathology itself can alter the circadian clock and its outputs. Here, I show that astrocyte-specific disruption of the circadian clock via deletion of the clock gene Bmal1 surprisingly decreased intra-neuronal protein pathologies. Further investigation found that deletion of the circadian clock resulted in a transcriptomic profile …

Fructose Promotes The Growth Of Tumors Through Metabolite Exchange With Non-Malignant Tissues, Ronald Joseph Fowle-Grider

Arts & Sciences Graduate Student Theses and Dissertations

The amount of dietary fructose consumed in the United States has increased considerably over the past five decades, largely due to the widespread use of high fructose corn syrup as a sweetener. The potential link between this elevated fructose intake and the development of cancer remains incompletely understood. Here we show that, even though cervical cancer cells themselves cannot directly utilize fructose carbon, diets high in fructose enhance the growth of cervical tumors by nearly threefold in mice. We demonstrate that efficient utilization of fructose carbon requires ketohexokinase-C, which was not expressed in ~100 cervical tumors that we examined from …

Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard

Arts & Sciences Graduate Student Theses and Dissertations

The Williams Syndrome Critical Region (WSCR) at chromosome 7q11.23 provides a unique opportunity to untangle the relationship between genotype and phenotype in complex behaviors, from fear and anxiety to sociability and sensorimotor processing. Copy number variations (CNVs) in this region result in two syndromes, Williams Syndrome (WS) and Duplication 7q11.23 Syndrome (Dup7), which display phenotypes that may align, indicating a common disruption of a system, or diverge, reflecting an underlying gene dosage-dependent effect. While case studies of atypical deletions resulting in WS have implicated telomeric genes Gtf2ird1 and Gtf2i in the cognitive and behavioral profiles of WS, proving causation requires …

Characterizing Complex Affective Processing Across Age And In Relation To Social Anxiety Symptoms, M. Catalina Camacho

Arts & Sciences Graduate Student Theses and Dissertations

Humans require a shared understanding of others’ emotions for adaptive social functioning. For instance, if someone tells a joke and another person laughs, we assume the laughing person was happy because we have a shared concept for such positive interactions. Children develop and refine these concepts as they grow up, but the underlying neural processing that supports this development is unknown. Identifying the neurodevelopment underlying emotion processing could provide important insight to emotional disorders. For example, social anxiety is associated differences in the detection and interpretation of negative or neutral emotional cues, but the underlying neurodevelopment of this behavior is …