Life Sciences Commons^™

Using A Reverse Visually Guided Reaching Task To Distinguish Between Healthy Aging And Early Alzheimer’S Disease, Brandon Woolman

Dissertations, Master's Theses and Master's Reports

Changes in motor behavior may function as a proxy for cognitive decline. While Alzheimer's disease (AD) is associated with impairments in learning and memory, recent studies suggest that subtle changes in motor task performance may reflect early cognitive changes. For example, the visuomotor rotation task that manipulates visual feedback about hand position during reaching movements, can be used to examine cognitive changes in aging populations. The current study used the reverse visually guided reaching task (rVGR) which rotates visual feedback of participant’s hand position 180⁰ relative to the actual hand position. We sought to expand on previous literature by recruiting …

Exploring The Molecular Pathways Of Cell Death Induced By Pde3 Modulators, Aqsa Ahsan

Dissertations, Master's Theses and Master's Reports

Metabolic dysregulation, a critical hallmark of cancer, predisposes potential vulnerabilities for the development of targeted therapy. LKB1, a pivotal metabolic regulator and tumor suppressor, is often lost in many cancers. Our laboratory has unveiled that LKB1 suppresses phosphodiesterases (PDEs), and PDE3 modulators can selectively eradicate LKB1-deficient tumor cells. Through metabolic gene sgRNA library screening, Sarcolipin, an inhibitor of Sarcoendoplasmic Reticulum Calcium ATPase (SERCA), emerged as essential for cell death in this context. However, the precise molecular mechanisms by which PDE3 modulators exert their effects remain elusive. This study aims to uncover these mechanisms via RNA-Seq profiling and differential gene analysis, …

Exploring Usability In Exercise Interventions: From Conceptualization To Measurement And Application, Anne Inger Mørtvedt

Dissertations, Master's Theses and Master's Reports

Exercise interventions hold promise for preventing and treating numerous conditions, diseases, and injuries. However, these interventions will only be effective if they are being used. Unfortunately, uptake and adherence to prescribed exercise and physical activity guidelines are insufficient. Some reasons for this include lack of knowledge, resources, flexibility, and enjoyment. Exercise program developers need to not only consider the effectiveness of the program during the development phase, but also involve end-users and receive feedback on program usability to determine likelihood of uptake and adoption. Usability testing can be used to detect barriers to use and implementation likelihood but has not …

Chemical Synthesis Of Sensitive Dna, Komal Chillar

Dissertations, Master's Theses and Master's Reports

Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …

The Effects Of Experimental Warming On Root Respiration And The Fungal Community Of Tropical Forest Soil, Malik A. Sankofa

Dissertations, Master's Theses and Master's Reports

Climate induced changes in tropical forests fungal communities could impact diversity and abundance, forest health, and carbon release/sequestration. Under warmer soil temperatures and over time, we hypothesized that arbuscular mycorrhizal, pathogen, saprotroph diversity and abundance would increase, that ectomycorrhizal and overall fungal diversity and abundance would decrease, and that root respiration would be unaffected. Experimental warming (+2-3 ℃) was conducted on root ingrowth cores at the Tropical Responses to Altered Climate Experiment (TRACE) in Puerto Rico. ITS2 metabarcoding was used to analyze fungal diversity and abundance in control or warmed root/soil samples. We found that warming decreased arbuscular mycorrhizal diversity, …

Silphid And Carabid Beetles In An Experimental Forest Trial: Idna And Diets, And Insect-Human Relationships Can Better Inform Forest Management, Katherine E. Higdon

Dissertations, Master's Theses and Master's Reports

Insect conservation, primarily focused on pollinators, is a growing issue amid concerns of climate change and the purported sixth mass extinction of Earth’s biodiversity. However, the focus on charismatic pollinators ignores a large portion of ecologically important and beneficial species. Having broader knowledge of insect diets and the impacts of anthropogenic disturbance on diets can better inform more comprehensive management approaches while also providing valuable knowledge with regards to trophic relationships between multiple species within ecosystems. This ensures the health and stability of ecosystems beyond pollination services. This research started by establishing the utility of Silphid beetles for invertebrate DNA …

Hydrologic Pathways Of A Northern Hardwood Catchment In The Great Lakes Basin Using End Member Mixing Analysis, Cory C. Burkwald

Dissertations, Master's Theses and Master's Reports

This study investigated the seasonality of hydrologic pathways, the role of wetlands in streamflow generation, and how hydrologic pathways affect the export of nutrients by streamflow in the Sturgeon River using endmember mixing analysis. The results indicated that streamflow consists of three main components: shallow subsurface water from wetland soils, shallow groundwater, and surface runoff from precipitation. Snowmelt plays a dominating role in regulating stream water chemistry (~80% volume at peak) during the snowmelt season and likely also after that. Wetland soils store snowmelt, together with rainwater though the fraction is unknown, and then gradually release through summer in the …

Assessing Tropical Mammal Diversity And Distribution Using Noninvasive Methods, Tiff L. Degroot

Dissertations, Master's Theses and Master's Reports

Central African tropical forests are rich in biodiversity and home to some of Earth’s most threatened mammals. However, mammals in the region are under increasing threat from habitat loss and degradation, coupled with an increased demand for wild meat. To conserve mammals, wildlife managers and community-led conservation efforts must understand the distribution and diversity of mammal communities. However, funding and logistical challenges make contemporary survey methods, e.g. ground surveys, difficult and expensive. Noninvasive methods allow efficient mammal diversity surveys with minimal field effort. Here, we use camera trapping and invertebrate-derived environmental DNA (“iDNA”) to assess mammal diversity and distribution in …

A Multimolecular Perspective On The Success Of Wolf Recovery And Relocation, Samuel D. Hervey

Dissertations, Master's Theses and Master's Reports

With global biodiversity in decline and many species isolated in fragmented habitats, conservation efforts increasingly rely on natural recolonization and translocation to restore ecosystems. These strategies face challenges such as genetic erosion and habitat limitations, highlighting the need for effective monitoring practices. This research assesses the success of wolf recovery initiatives by examining long-term genetic and genomic health using both traditional and advanced molecular methods. First, we investigated the genetic health of 19 gray wolves (Canis lupus) relocated to Isle Royale National Park to restore ecosystem balance. Initial genetic assessments with microsatellites found that these wolves had genetic diversity metrics …

Validation And Improvement Of Forest Health Risk Maps: A Case Study With Maple Decline/Dieback, Joseph R. Beeson

Dissertations, Master's Theses and Master's Reports

Forest health data collected in a two-phased survey of maple dieback was used to build on previous work, extending analysis into mapping implications. Using the National Insect and Disease Risk Maps (NIDRM) published by the US Forest Service as a baseline, we compared our collected data from 2009-2012 and 2021-2022 with the published 240m resolution sugar maple decline risk map, finding the NIDRM map to be a poor predictor of sugar maple dieback measured at the plots. Measured sugar maple crown dieback was also compared to measured soil characteristics and nutrient levels, and augmented with soil survey maps and long-term …

Chemical Synthesis And Biological Application Of Sensitive Rna, Alexander T. Apostle

Dissertations, Master's Theses and Master's Reports

In the field of epigenetics - the dynamic collection of chemical modifications that overlay DNA/RNA - there is increasing interest in the potential for therapeutic and research-based utilization of the epitranscriptomics: those epigenetic modifications specific to RNA. Epitranscriptomics can give us a new approach to understanding and treating RNA viruses, like SARS-CoV-2. Given viruses are often found modified by human epitranscriptomic machinery, understanding how these modifications can modulate virulence is of high interest. We have shown that the N1-methyladensoine modification causes RNA synthesis termination in the SARS-CoV-2 replication complex, and thus may explain the differences in symptoms observed in individuals. …

The Role Of Neighborhood Effects In Maintaining The Hardwood-Hemlock Mosaic, Adam Z. Milenkowic

Dissertations, Master's Theses and Master's Reports

Neighborhood effects are processes mediated by canopy trees that influence the ability of a species to replace itself following canopy mortality. Sugar maple (Acer saccharum Marsh.) and eastern hemlock (Tsuga canadensis (L.) Carr.) are the dominant trees in old-growth northern hardwood forests of Upper Michigan and have been observed to form monodominant patches in the region. Few studies have independently evaluated the demographic and ecological mechanisms that lead to the compositional stability of hemlock and sugar maple patch development. Tree demography data from eight long-term 0.5 ha old-growth plots in Upper Michigan indicate neighborhood effects are playing a …

Synthesis Of Long Oligodeoxynucleotides, Yipeng Yin

Dissertations, Master's Theses and Master's Reports

Synthetic long oligodeoxynucleotides (ODNs) have found wide applications in diverse fields such as chemical biology, synthetic biology, and genes and genomes synthesis. Those applications leading to a significant demand for their production. However, traditional methods for purifying synthetic ODNs present notable drawbacks, particularly their inability to purify long ODNs, rendering long ODN synthesis challenging. To address these issues, chemical synthesis techniques for long ODNs coupled with non-chromatographic purification methods have been developed. This technology makes the purification of long synthetic ODNs feasible and offers a viable pathway for producing genes and genomes with extensive repeats or stable secondary structures, which …

Nitrogen Uptake Rates And Phytoplankton Composition Across Contrasting North Atlantic Ocean Coastal Regimes North And South Of Cape Hatteras, Yifan Zhu, Margaret R. Mulholland, Peter W. Bernhardt, Aimee Renee Neeley, Brittany Widner, Alfonso Macías Tapia, Michael E. Echevarria

OES Faculty Publications

Understanding nitrogen (N) uptake rates respect to nutrient availability and the biogeography of phytoplankton communities is crucial for untangling the complexities of marine ecosystems and the physical, biological, and chemical forces shaping them. In the summer of 2016, we conducted measurements of bulk microbial uptake rates for six ¹⁵N-labeled substrates: nitrate, nitrite, ammonium, urea, cyanate, and dissolve free amino acids across distinct marine provinces, including the continental shelf of the Mid-and South Atlantic Bights (MAB and SAB), the Slope Sea, and the Gulf Stream, marking the first instance of simultaneously measuring six different N uptake rates in this dynamic region. …

Heterogeneity Of Nitrogen Fixation In The Mesopelagic Zone Of The South China Sea, Siqi Wu, Xianhui Sean Wan, Moge Du, Xirong Chen, Corday R. Selden, Mar Benavides, Sophie Bonnet, Carolin R. Löscher, M. Robert Hamersley, Margaret R. Mulholland, Xiuli Yan, Shuh-Ji Kao

OES Faculty Publications

Biological dinitrogen (N₂) fixation, the energetically expensive conversion of N₂ gas to ammonia, plays an essential role in balancing the nitrogen budget in the ocean. Accumulating studies show detectable N₂ fixation rates below the euphotic zone in various marine systems, revealing new insights of marine N₂ fixation. However, the reported rates are highly variable and frequently fall close to detection limits, raising the question of the ubiquity and significance of N₂ fixation in the global dark ocean. Using highly sensitive isotopic labeling incubation including a set of control incubations, we confirm the occurrence of mesopelagic N₂ fixation in the South …

Measuring Spontaneous Neurotransmission Using Genetically Encoded Fluorescent Indicators, Amelia Jane Ralowicz

Dartmouth College Ph.D Dissertations

Synaptic connections throughout the nervous system exhibit two forms of neurotransmitter release caused by synaptic vesicle fusion, evoked and spontaneous release. Despite being discovered 70 years ago, the mechanisms governing spontaneous release have remained elusive. Our understanding of spontaneous release lacks mechanistic details including discrepancies in the sources of synaptic vesicles supporting it, the source(s) of calcium supporting it, and most importantly an unclear relationship (cooperative or antagonistic) with evoked release. These gaps exist due to a lack of experimental methods specific to the study of spontaneous release at individual synapses.

This thesis addresses these gaps in two ways. Firstly, …

Identification And Therapeutic Targeting Of Metabolic Alterations In Estrogen Receptor-Positive Breast Cancer, Steven Tau

Dartmouth College Ph.D Dissertations

Estrogen receptor-positive breast cancer remains one of the most frequently diagnosed cancers in women. Despite adjuvant endocrine therapy reducing the rate of recurrence, there remains a significant proportion of patients whose breast cancer will recur years to decades after the initial diagnosis. The underlying biology of tumor cells in the period between initiation of adjuvant therapy and recurrence is relatively unexplored, preventing the development of better treatment options. From a genome-wide screening approach, we identified and characterized broad metabolic reprogramming associated with the persistent cell state. We demonstrate that a decreased ability to metabolize glucose in turn pushes a higher …

Near-Infrared Paired-Agent Imaging For In Vivo Quantification Of Receptor Occupancy In Tumor, Yichen Feng

Dartmouth College Ph.D Dissertations

Accurate assessment of drug receptor occupancy (RO) holds significant importance in both drug development and personalized medicine, as it facilitates quantitative characterization of dose-response relationship for a given drug. This information not only aids appropriate dose selection for clinical trials but also guides personalized dose optimization in precision medicine.

Molecular imaging, utilizing receptor-specific imaging agents for tissue visualization, has emerged as the major option for in vivo measurement of tissue RO. Nonetheless, the abnormal yet complex structure and hemodynamics of tumors often lead to substantial non-specific uptake and retention of imaging agents, thus introducing significant bias to RO measurements. To …

Exploring 3d Genome Interaction And Epigenetic Regulation Via Swi/Snf Complex And Deep Learning Models, Ruoyun Wang

Dartmouth College Ph.D Dissertations

The three-dimensional organization of the genome is fundamental in regulating gene expression and maintaining cellular function. This organization's complexities, influenced by epigenetic marks and chromatin remodeling complexes, are crucial for understanding genomic regulation. Among these, the SWI/SNF complexes are key, facilitating chromatin accessibility and regulating gene activity across cell types. The first part of my dissertation focuses on SWI/SNF complexes, exploring their role in chromatin remodeling and their impact on 3D genome architecture. Utilizing next-generation sequencing (NGS) techniques, this section investigates the interplay between these complexes and chromatin structure. During my research on the SWI/SNF complex, I was intrigued by …

Biogenesis And Function Of Microglial Extracellular Vesicles In Neuroinflammation And Parkinson’S Disease, Karl E. Biggs

Dartmouth College Ph.D Dissertations

Microglia are subject to chronic proteinaceous and environmental stress during the progression of prevalent neurodegenerative diseases such as Parkinson’s Disease (PD). Chronic stress can activate the NLR family pyrin domain containing 3 (NLRP3) pattern recognition receptor resulting in the formation of the NLRP3 inflammasome, proinflammatory signaling, and pyroptotic cell death. A distinct subset of extracellular vesicles (EVs) are released from cells upon NLRP3 activation. We studied WT and Nlrp3^-/- primary microglia exposed to bacterial stimulating agents and alpha synuclein preformed fibrils (αsyn PFFs), which model Parkinson’s disease and associated synucleinopathies. We identified the NLRP3-dependent release of the endosome fate …

Chromatin Regulation By Swi/Snf Remodelers In Somatic Stem Cell Maintenance And Transformation, Luke Thomas Deary

Dartmouth College Ph.D Dissertations

Cell identity is defined by the epigenome, whereby chromatin regulators work in concert to promote gene expression programs that serve a cell’s specialized purpose. Mutations in chromatin regulators are amongst the most frequent drivers of human disease, underscoring the importance of understanding their activities in maintaining cell identity and tissue function. In particular, mutations in subunits of the evolutionarily conserved SWI/SNF chromatin remodeling complexes drive diseases across human tissues in both development and adult tissue maintenance5. Three major SWI/SNF complexes exist: BAF, PBAF, and GBAF, which differ in their composition and genomic targeting but share an ATP-dependent catalytic activity to …

Investigating The Mechanisms For Priming And Maintaining Tumor Ag Specific Cd8+ T Cell Responses In The Context Of Cd4-Depletion, Delaney E. Ramirez

Dartmouth College Ph.D Dissertations

Achieving durable, systemic CD8+ T cell responses against tumors is an imperative goal in treating cancer. However, suppressive cells, including Foxp3+CD4+ regulatory T cells (Tregs) are widely recognized to inhibit CD8+ T cell activity. For nearly two decades, anti-CD4 treatment has been used to eliminate Tregs and induces durable tumor antigen (Ag) specific CD8+ T cells, despite also depleting Foxp3-negative conventional CD4+ T (Tconv) cells. However, the underlying mechanism of anti-CD4 efficacy is not understood. In Chapter Three, we look beyond Treg depletion and investigate the potential contributions of other factors including homeostatic space, depletion of CD4+ APCs, and presence …

Estrogen Receptor (Er) Alpha Regulatory Mechanisms And Therapeutic Strategies In Er+ Breast Cancer, Bianca A. Romo

Dartmouth College Ph.D Dissertations

Breast cancer is among the most frequently diagnosed cancers in the U.S. and is one of the leading causes of cancer-related mortalities, second to lung cancer. Estrogen receptor alpha-positive (ER+) breast cancer accounts for 2/3 of diagnosed cases. Patients diagnosed with this subtype of breast cancer typically undergo endocrine therapy that aims to mitigate the growth-promoting effects of estrogen/ER. While therapies are effective, 1/3 of patients will experience recurrence. To begin addressing this drug-resistant patient population, we investigated potential drug targets involved in response to treatment.

Coregulators have been implicated in the regulation of ER transcriptional activity and subsequently affecting …

Target Selection And Enhancement During Attentional Tracking, Marvin R. Maechler

Dartmouth College Ph.D Dissertations

At any waking moment, we are bombarded with more sensory information than we can fully process. Attention is necessary to deal with the dynamic world we live in. One fundamental function of vision and attention is to keep track of moving objects, but what are the targets of attention during tracking?

One of the first theories of attentional tracking predicted that targets would be selected at early processing stages. By employing the double-drift illusion, which dissociates physical and perceived positions of moving objects, we investigated which of these positions is selected for tracking. Contrary to earlier theories and in line …

Exact Testing For Heteroscedasticity In A Two-Way Layout In Variety Frost Trials When Incorporating A Covariate, Angelika A. Pilkington, Brenton R. Clarke, Dean A. Diepeveen

Grain and Other Field Crops Research Articles

Two-way layouts are common in grain industry research where it is often the case that there are one or more covariates. It is widely recognised that when estimating fixed effect parameters, one should also examine for possible extra error variance structure. An exact test for heteroscedasticity, when there is a covariate, is illustrated for a data set from frost trials in Western Australia. While the general algebra for the test is known, albeit in past literature, there are computational aspects of implementing the test for the two way when there are covariates. In this scenario the test is shown to …

Investigation Of The Ecological Interactions And Host Specificity Of Verticillium Nonalfalfae, A Proposed Biological Control Agent Against The Invasive Tree-Of-Heaven (Ailanthus Altissima), Kristen H. Pierce

Graduate Theses, Dissertations, and Problem Reports (ETD)

Tree-of-heaven (Ailanthus altissima) is a highly invasive tree species with a cosmopolitan distribution, including an expansive range in North America. In the U.S., tree-of-heaven has established populations in more than 40 states and is considered among the most notorious of invasive plant species. The discovery of Verticillium nonalfalfae and V. dahliae causing acute wilt and mortality of Ailanthus in the mid-Atlantic in the 2000s has resulted in numerous studies evaluating the utility of these fungi as potential biocontrol agents. Recent efforts to commercialize V. nonalfalfae have raised additional questions about its widespread use and factors influencing long-term efficacy. …

Aberrant Lipid Accumulation And Retinal Pigment Epithelium Dysfunction In Prcd-Deficient Mice, Sree Indrani Motipally

Graduate Theses, Dissertations, and Problem Reports (ETD)

Progressive Rod-Cone Degeneration (PRCD) is a peripheral membrane protein predominantly expressed in photoreceptor outer segment (OS) disc membranes with an unknown function. Several mutations in Prcd are implicated in Retinitis pigmentosa (RP) in humans. The most common “cysteine to tyrosine” (C2Y) mutation in Prcd leads to progressive retinal atrophy in multiple dog breeds and RP in humans. Canine models harboring the C2Y mutation in Prcd show disorganized OS structure with greatly attenuated photoreceptor OS renewal rates. Recent studies show defects in the photoreceptor nascent disc flattening in the absence of Prcd. However, it is unclear how OS discs eventually …

Genetic And Transcriptomic Investigations Of Progressive Ethanol Consumption In The Diversity Outbred Mouse, Zachary Tatom

Theses and Dissertations

As a complex genetic disorder, alcohol use disorder (AUD) is thought to be influenced by many genes each contributing only a small effect to the overall disease liability. Dozens of genes have been implicated as potentially affecting risk for AUD and alcohol consumption. However, understanding the full genetic architecture of AUD – what genes are involved, to what extent, and how these genes are regulated – remains a challenging step in identifying novel treatments. Gene expression studies in humans have attempted to augment GWAS of alcohol consumption but are often confounded by environmental factors; the difficulty of collecting tissue from …

Mortality Index Of Drosophila Melanogaster, Following Traumatic Brain Injury, Megan N. Ashworth

Graduate Student Dissertations, Theses, Capstones, and Portfolios

Traumatic brain injuries (TBI) are associated with immediate and long-term consequences that can be divided into primary and secondary injuries. A primary injury results due to the direct damage inflicted on the brain by the hit, whereas a secondary injury takes more time to manifest due to the cascade of molecular events that lead to cellular damage and death within the brain. This study analyzes mortality as a secondary injury following traumatic brain injury in the presence of a human neurodegenerative genetic risk factor, APOE ε4. The High Impact Trauma (HIT) device developed by Katzenberger et al. (2013) was utilized …

Biodistribution Comparison Of Fentanyl And Morphine Following Acute And Repeated Expsoure, Rosamond M. Goodson

Theses and Dissertations

The ongoing opioid crisis constitutes a dire public health threat that has resulted in staggering loss of life. In 2021, opioids were implicated in over 75% of the approximately 107,000 deaths attributed to drug overdose (CDC), and synthetic opioids such as fentanyl and its analogues are key drivers of the surge in opioid fatalities in recent years. Although fentanyl is a μ opioid receptor agonist, it has several distinct attributes compared to other drugs in this category, such as morphine. These include enhanced lipophilicity, heightened potency to induce respiratory depression, more rapid entry into the central nervous system, reduced sensitivity …