Digital Commons Network^™

Multi-Scale Simulations Of Dynamic Protein Structures And Interactions, Yumeng Zhang

Doctoral Dissertations

Intrinsically disordered proteins (IDPs) are functional proteins that lack stable tertiary structures in the unbound state. They frequently remain dynamic even within specific complexes and assemblies. IDPs are major components of cellular regulatory networks and have been associated with cancers, diabetes, neurodegenerative diseases, and other human diseases. Computer simulations are essential for deriving a molecular description of the disordered protein ensembles and dynamic interactions for mechanistic understanding of IDPs in biology, diseases, and therapeutics. However, accurate simulation of the heterogeneous ensembles and dynamic interactions of IDPs is extremely challenging because of both the prohibitive computational cost and demanding force field …

The Evolution And Development Of Awns In The Grass Subfamily Pooideae, Erin L. Patterson

Doctoral Dissertations

This research focuses on a specific example of replicated evolution: the grass awn. Awns are typically extensions of the lemma, but may also appear on glumes or paleas. The lemma is a leaf-like organ on the exterior of the grass flower, the glumes are a pair of bracts subtending the basic unit of grass inflorescences, the spikelet, and the palea is the floral organ opposite the lemma. Awns are often described as "hair-" or "bristle-" like, but appear in many different shapes. Many awns are “twisted & geniculate", in which the awn has two sections, a lower twisted column, and …

Investigating The Escape Mechanism Of Sre Bearing Mrna Transcripts During Viral Host Shutoff, Daniel Macveigh-Fierro

Doctoral Dissertations

During viral infection, the virus and host clash for control over gene expression in an evolutionarily arms race that has raged for thousands of years. During lytic replication, Kaposi’s sarcoma associated herpesvirus (KSHV) triggers a massive RNA decay event known as host shut off. This causes over 70% of all RNA to be degraded suppressing the host antiviral response while freeing resources for viral replication. Our lab focuses on a subset of transcripts that escape from this viral degradation event using a cis acting 3’ UTR element known as a “SOX resistant element” or SRE. Although we have identified a …

Associations Between Early Childhood Sleep, Memory Function, And Brain Development Across The Nap Transition, Sanna Lokhandwala

Doctoral Dissertations

Preschool-age children often distribute their sleep across a midday nap and overnight sleep. Skipping the nap is suggested to increase the duration and depth of deep sleep (i.e., slow wave activity; SWA). Moreover, missing the midday nap has been shown to impair learning processes. This may be because children’s brains at this point in development are immature, necessitating the intervening nap period to strengthen memories before they are forgotten. Nonetheless, at some point during the preschool years, many children begin transitioning naturally out of napping. It is unclear whether the memory benefits of overnight SWA after a skipped nap depend …

Analysis Of Micro(Nano)Plastics In Food Using Raman Microscopy, Xin Guo

Doctoral Dissertations

Microplastic pollution has emerged as a global concern in both aquatic and terrestrial environments. The presence of microplastics in the food chain poses a potential threat to human health. To accurately assess the risks associated with microplastics, it is crucial to have a reliable analytical technique capable of detecting, quantifying, and identifying microplastics of varying materials, sizes, and shapes in environmental, agricultural, and food samples. Spectroscopic techniques, specifically vibrational spectroscopy (Raman and Infrared), are extensively utilized in microplastic analysis. These techniques enable rapid and high-throughput identification, while also providing size and shape information. However, there are certain gaps in the …

High Resolution Mass Spectrometry As A Platform For The Analysis Of Polyoxometalates, Their Solution Phase Dynamics, And Their Biological Interactions., Daniel T. Favre

Doctoral Dissertations

Polyoxometalates (POMs) are a class of inorganic molecule of increasing interest to the inorganic, bioinorganic and catalytic communities among many others. While their prevalence in research has increased, tools and methodologies for the analysis of their fundamental characteristics still need further development. Decavanadate (V10) specifically has been postulated to have several unique properties that have not been confirmed independently. Mass spectrometry (MS) and its ability to determine the composition of solution phase species by both mass and charge is uniquely well suited to the analysis of POMs. In this work we utilized high-resolution mass spectrometry to characterize V10 in aqueous …

A Ground-Based L-Band Radar System For Monitoring Forest Temporal Dynamics, Xingjian Chen

Doctoral Dissertations

L-band FMCW radar is implemented for monitoring forest dynamics. It took short-term and long-term measurements with an internal calibration system that guarantees stability and precision. The radar data is compared to in-situ measurement, which infers causal relationships between radar backscatter signal and forest physiology index such as tree dielectric. This paper explains the relationship between radar signals and environmental components such as precipitation based on the measurement. The radar demonstrates some interesting observations, for example, trees' daily activity and freeze-thaw process.

The Impacts Of Environment And Host Evolutionary Relationships On Lemur Microbiota, Rachel B. Burten

Doctoral Dissertations

Recent studies have shown that the mammal microbiome is modified by environmental conditions, and that reduced microbiome functionality is associated with host health issues. Microbiome data in wild and captive primate populations can therefore be used to assess their health as they encounter a variety of environments. Comparative studies of the microbiome can also inform disease ecology, conservation, and captive management strategies tailored to different primate species. Therefore, this study examines how the hair, oral, and gut microbiota of nine wild and captive lemur species are determined by host phylogenetic relationships and host environment. I found that host species identity …

The Wild Tomato Clade Offers Insights Into Fleshy Fruit Trait Evolution At The Phenotypic And Molecular Levels, Jacob R. Barnett

Doctoral Dissertations

Biologists have long been fascinated by the diversity of fleshy fruits, yet questions remain as to how this variety has evolved. According to the dispersal syndrome hypothesis, flowering plants improved their reproductive success by producing fleshy fruits with appealing combinations of traits that attract animal dispersers. However, animal preferences may not be the only selective pressure driving fruit trait diversity—conflicting forces include damage-inflicting seed predators and pathogens, abiotic habitat conditions, or constraints stemming from non-adaptive mechanical, developmental, or phylogenetic limitations. Few studies have examined the early stages of fleshy fruit evolution across an entire clade of recently diverged plant species. …

Development Of An Integrated Workflow For Nucleosome Modeling And Simulations, Ran Sun

Doctoral Dissertations

Nucleosomes are the building blocks of eukaryotic genomes and thus fundamental to to all genetic processes. Any protein or drug that binds DNA must either cooperate or compete with nucleosomes. Given that a nucleosome contains 147 base pairs of DNA, there are approximately 4^147 or 10^88 possible sequences for a single nucleosome. Exhaustive studies are not possible. However, genome wide association studies can identify individual nucleosomes of interest to a specific mechanism, and today's supercomputers enable comparative simulation studies of 10s to 100s of nucleosomes. The goal of this thesis is to develop and present and end-to-end workflow that serves …

Exploring Soil Microbial Dynamics In Southern Appalachian Forests: A Systems Biology Approach To Prescribed Fire Impacts, Saad Abd Ar Rafie

Doctoral Dissertations

Prescribed fires in Southern Appalachian forests are vital in ecosystem management and wildfire risk mitigation. However, understanding the intricate dynamics between these fires, soil microbial communities, and overall ecosystem health remains challenging. This dissertation addresses this knowledge gap by exploring selected aspects of this complex relationship across three interconnected chapters.

The first chapter investigates the immediate effects of prescribed fires on soil microbial communities. It reveals subtle shifts in porewater chemistry and significant increases in microbial species richness. These findings offer valuable insights into the interplay between soil properties and microbial responses during the early stages following a prescribed fire. …

The Identification Of Small Molecule Inhibitors To Candida Albicans Phosphatidylserine Synthase, Yue Zhou

Doctoral Dissertations

Candida albicans phosphatidylserine (PS) synthase, encoded by the CHO1 gene, has been identified as a potential drug target for new antifungals against systemic candidiasis due to its importance in virulence, absence in the host and conservation among fungal pathogens. This dissertation is focused on the identification of inhibitors for this membrane enzyme. Cho1 has two substrates: cytidyldiphosphate-diacylglycerol (CDP-DAG) and serine. Previous studies identified a conserved CDP-alcohol phosphotransferase (CAPT) binding motif present within Cho1, and here we revealed that mutations in all but one conserved amino acid within the CAPT motif resulted in decreased Cho1. For serine, we have predicted a …

Characterization Of Radiotolerance In Potato And Development Of A Gamma Radiation Phytosensor., Robert Graham Sears

Doctoral Dissertations

As humans pursue space travel and nuclear energy, the risk of harm from ionizing radiation increases. On Earth or in space, plants are essential to our personal and environmental health. Plants serve as sentinels, bioremediators and food sources in areas of high ionizing radiation, therefore it is essential to understand how ionizing radiation affects plant biology. This work aimed to understand plant responses to ionizing radiation in the potato chassis and apply that knowledge to generate novel phenotypes for nuclear energy and space applications. The first gamma radiation phytosensor was developed for monitoring at standoff distances greater than three meters. …

Impact Of Cadmium Stress On Soil Virus Reproduction And The Persistence Of Viruses Under Abiotic Conditions, Zhibo Cheng

Doctoral Dissertations

Soil viruses are ubiquitous and greatly impact the structure and function of soil microbial communities, with their effects modulated by various environmental factors. This study investigates the inactivation of naturally occurring soil viruses in sterilized soil, as well as the effects of cadmium (Cd) exposure and carbon (C) and nitrogen (N) nutrient availability on the population dynamics of virus-host communities in agricultural soil.

Lab-scale slurry and unsaturated experiments were performed to examine virus inactivation in the absence of host bacteria in sterilized soil. In slurry experiments, virus abundance declined by over 90% after 10 days of incubation. The addition of …

Integration Of Raman Spectroscopy And Python-Based Data Analysis For Advancing Neurobiological Research, Natalie E. Dunn

Doctoral Dissertations

The field of Raman spectroscopy continues to expand into biological applications due to its usefulness as a non-invasive technique that can be utilized qualitatively and quantitatively. However, the inherent weakness of Raman scattering leads to the need for each collected spectra to undergo a preprocessing step to remove noise, background drift, and cosmic rays. Biological research in particular needs large datasets due to the increased variability in samples. As datasets grow, the need to perform preprocessing on each individual spectra becomes daunting. Often, these steps are done by hand with the help of specialized software programs. Preprocessing can be accelerated …

Characterization Of Lignin Structural Variability And The Associated Application In Genome Wide Association Studies, Nathan D. Bryant

Doctoral Dissertations

Poplar (Populus sp.) is a promising biofuel feedstock due to advantageous features such as fast growth, the ability to grow on marginal land, and relatively low lignin content. However, there is tremendous variability associated with the composition of biomass. Understanding this variability, especially in lignin, is crucial to developing and implementing financially viable, integrated biorefineries. Although lignin is typically described as being comprised of three primary monolignols (syringyl, guaiacyl, p-hydroxyphenyl), it is a highly irregular biopolymer that can incorporate non-canonical monolignols. It is also connected by a variety of interunit linkages, adding to its complexity. Secondary cell wall …

Regulation Of Protein Synthesis In Arabidopsis Thaliana Through A Bioinformatic And Mathematical Lens, Ricardo Andres Urquidi Camacho

Doctoral Dissertations

Organisms exist under constantly varying environmental and internal conditions, which necessitate the differential regulation of gene expression. To synthesize proteins, the ribosome translates the information encoded in the nucleotide sequence of an mRNA into the final, functional amino acid sequence. Knockouts of ribosomal proteins lead to lethality. One such protein is the ribosomal protein 6 of the small subunit (eS6/RPS6). We confirmed that the knockout of either one of two eS6 paralogs in Arabidopsis leads to stunted growth and chlorosis. Here, these phenotypes have been further characterized in seedlings by precisely quantifying the ribosome loading of mRNAs as well as …

Exploring The Regulation Of A Bacillus Pumilus Bioplastic Degrading Protein, Elise Keara Phillips

Doctoral Dissertations

Biodegradable plastics are being adopted to reduce the environmental impacts associated with petroleum-based plastics, including long residence times, and reliance on fossil fuels as a feedstock. Microbial degradation of bioplastics is still poorly understood, which leads to inconsistent degradation outcomes and challenges for implementation. Bacillus pumilus B12 degrades the biodegradable bioplastic polylactic acid (PLA) via the protease AprE, but the regulatory mechanisms controlling aprE expression in B. pumilus B12 are largely unknown. To explore this question, we established developed a conjugation- based method to introduce DNA into B. pumilus B12 and diverse Bacillus species that is applicable to environmental and …

Novel Microbial Guilds Implicated In N2o Reduction, Guang He

Doctoral Dissertations

N₂O is a long-recognized greenhouse gas (GHG) with potential in global warming and ozone depletion. Terrestrial ecosystems are a major source of N₂O due to imbalanced N₂O production and consumption. Soil pH is a chief modulating factor controlling net N₂O emissions, and N₂O consumption has been considered negligible under acidic conditions (pH <6). In this dissertation, we obtained solids-free cultures reducing N₂O at pH 4.5. Furthermore, a co-culture (designated culture EV) comprising two interacting bacterial population was acquired via consecutive transfer in mineral salt medium. Integrated phenotypic, metagenomic and metabolomic analysis dictated that the Serratia population excreted certain …

Influences Of High-Fat Diet And Antrodia Camphorata In Early Life On Intestinal Tumorigensis Later In Life, Ting-Chun Lin

Doctoral Dissertations

Young-onset colorectal cancer (CRC) is a growing public health concern globally due to the increasing prevalence of westernized lifestyles during childhood and adolescence. Meanwhile, there have been reports of health-promoting effects, such as anti-inflammatory and anti-cancer properties, associated with Antrodia camphorata (AC), a unique fungus native to Taiwan. This study aimed to investigate the impact of early-life high-fat diet (HF) and AC supplementation on intestinal tumorigenesis in young adulthood, using APC^1638N mice. Additionally, the study aimed to determine the role of Turicibacter, a probiotic negatively associated with diet-induced obesity, in colorectal tumorigenesis, and to explore the anti-cancer mechanism …

Detection And Control Of Environmentally Transmissible Viruses, Anand R. Soorneedi

Doctoral Dissertations

Viruses, owing to their ubiquitous nature and ability to infect almost every other species, have long been a subject of interest for scientists. Some of the virus species can be very deadly to humans and animals alike and can impose a huge economic and health burden across the world. The recent CoVID-19 pandemic underscores the importance of timely detection for developing effective intervention strategies. Unfortunately, some of the virus species that cause significant health and economic impacts do not have robust and reliable detection methods due to several reasons. In some cases, despite having gold standard methods for detection of …

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Understanding And Developing Safer Sanitation Agents And Strategies In Food Production Environments, Pragathi Kamarasu

Doctoral Dissertations

Food is a primary resource for survival of human beings, and it is also one of the primary resources for spread of infectious diseases. When both these factors come together it does not only cause ill effects on our health but also causes a burden on the food and agricultural industry. Through the help of science, us researchers and scientists have always tried to reduce this burden. And I hope like a drop of water in the ocean in some way my research contributes towards this. According to WHO currently in 2023 there are about 1 in 10 people falling …

Chemical Modification And Evaluation Of Cells Towards Use As Delivery Tools, Bishnu Prasad Joshi

Doctoral Dissertations

CHEMICAL MODIFICATION AND EVALUATION OF CELLS TOWARDS USE AS DELIVERY TOOLS SEPTEMBER 2023 BISHNU PRASAD JOSHI M.S., SRI SATHYA SAI INSTITUTE OF HIGHER LEARNING Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Michelle E. Farkas Endogenous cells are being studied for use in various applications, such as next generation therapeutics and drug delivery vehicles. This is on account of their biocompatibility, amenable distribution profiles, and in many instances, recruitment to and localization of diseased tissues. Multiple cell types have been employed, including macrophages, stem cells, red blood cells, and T cells. Most examples of cell-based delivery utilize phagocytosed entities as …

Investigating Brainstem Mechanisms Underlying Prepulse Inhibition Of Startle Impaired In Schizophrenia, Wanyun Huang

Doctoral Dissertations

Sensorimotor gating is a fundamental pre-attentive process, which can be operationally measured through prepulse inhibition (PPI) of the startle response. PPI describes the suppression of the startle response when a non-startling stimulus (“prepulse”) precedes the startling stimulus (“pulse”). As a hallmark of schizophrenia, PPI deficits are also found in other neuropsychiatric disorders and are associated with cognitive overload and attention impairments (Braff et al., 2001). However, currently-used dopaminergic antipsychotics exhibit inconsistent effects on PPI in affected individuals (Geyer et al., 2001; Frau et al., 2014; Lally et al., 2016). Therefore, it’s critical to investigate the precise cellular and synaptic mechanisms …

An Investigation Of The Role Of Amygdalar Circuits In The Production Of Social Behavior, Joseph Fd Dwyer

Doctoral Dissertations

Adaptive social behaviors allow animals to survive, thrive, and successfully reproduce. These behaviors, including mating, parenting, affiliation, and aggression, can be stereotyped in response to specific stimuli but often display sex-specific, and interoceptive-dependent variations in their execution. A conserved set of brain regions collectively known as the social behavior network (SBN) interprets sensory information about social cues and generates an appropriate behavioral response. In this dissertation I present 5 chapters. Chapter 1 introduces historical research focusing on the neural circuits that drive social behavior and the potential impact of environmental factors on the activity of these circuits. Chapter 2 describes …

A Biochemical Approach To Characterize A Divergent Trypanosoma Brucei Mitochondrial Dna Polymerase, Polib, Stephanie B. Delzell

Doctoral Dissertations

Trypanosoma brucei is a single-celled parasitic protist that causes African sleeping sickness in people and nagana in cattle in sub-Saharan Africa. T. brucei and related trypanosomatid parasites contain an unusual catenated mitochondrial genome known as kinetoplast DNA (kDNA) composed of dozens of 23 kb maxicircles and thousands of 1 kb minicircles. The kDNA structure and replication mechanism are divergent from other eukaryotes and essential for parasite survival. POLIB is one of three Family A DNA polymerases that are independently essential to maintain the kDNA network, and has been implicated in minicircle replication. However, the division of labor among the paralogs, …

Protein Trafficking In The Endoplasmic Reticulum Mediated By A Tpr-Containing Adapter Protein, Nathan P. Canniff

Doctoral Dissertations

The endoplasmic reticulum (ER) is a large, multifunctional organelle that acts as the entrance into the secretory pathway, which accounts for the folding and maturation of approximately one third of the human proteome. It is the largest organelle in most cell types and is comprised of a single lumen and a contiguous membrane. The ER is responsible for a multitude of roles including protein translocation, folding, maturation, quality control, and glycosylation to name a few. These processes are buoyed by a large collection of chaperones and cochaperones, the largest subfamily of which is characterized by the presence of tetratricopeptide repeat …

Analysis Of Antioxidant Synergism And Its Mechanisms In Different Food Systems, Ipek Bayram

Doctoral Dissertations

Lipid oxidation results in off-flavors, toxic aldehydes, and co-oxidation of proteins and color compounds. Combining antioxidants to achieve synergistic interactions has been practiced for decades to improve oxidative stability. Nevertheless, synergism mechanisms have been poorly understood and rarely studied. This dissertation examines the mechanisms of antioxidant synergism in a model system with α-tocopherol (α-TOC) and myricetin (MYR). The interactions between α-tocopherol and taxifolin (TAX) were also tested because it has structural similarities to myricetin but has a higher redox potential. The first part of this research focused on the antioxidant interactions between α-tocopherol and myricetin in stripped soybean oil-in-water emulsions …

Osmoregulation And Appetite Regulation In A Basal Vertebrate, The Sea Lamprey (Petromyzon Marinus), Jessica Norstog

Doctoral Dissertations

Lamprey (Petromyontiformes) are the oldest extant family in the vertebrate lineage, providing a unique phylogenetic position for studies on vertebrate evolution. As a basal vertebrate, sea lamprey (Petromyzon marinus) is an important species to understand evolution and comparative physiological mechanisms, including osmoregulation and appetite regulation. Sea lamprey has anadromous (native to the Atlantic Ocean) and landlocked (invasive in the Laurentian Great Lakes in North America) populations. In both populations of sea lamprey, the blind filter-feeding freshwater (FW) larvae burrow in stream sediments for until undergoing a hormonal-driven metamorphosis. During this phase, sea lamprey do not feed as major …