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Circuit-Specific Vulnerability In A Mouse Model Of Alzheimer's Disease, Samuel Brunwasser May 2025

Circuit-Specific Vulnerability In A Mouse Model Of Alzheimer's Disease, Samuel Brunwasser

Arts & Sciences Graduate Student Theses and Dissertations

The relationship between brainwide functional decline and accumulation of pathological protein aggregates in Alzheimer’s disease (AD) is complex and not well understood. A set of highly interconnected cortical regions known as the Default Mode Network (DMN) exhibits selective vulnerability to both functional decline and amyloid beta (Aβ) plaques in early AD. One possibility is that early Aβ accumulation in the DMN drives vulnerability. However, it is unknown whether there is something intrinsic to neuronal projections within the DMN that biases these circuits towards dysfunction. In this dissertation, I describe the development of a multisite in vivo electrophysiology pipeline for chronic …


Expanding The Druggable Proteome By Integrating Deep Learning With Molecular Simulations To Predict Cryptic Pockets, Artur Meller May 2025

Expanding The Druggable Proteome By Integrating Deep Learning With Molecular Simulations To Predict Cryptic Pockets, Artur Meller

Arts & Sciences Graduate Student Theses and Dissertations

Of the protein structures deposited in the Protein Data Bank, less than half have pockets suitable for the binding of drugs. Even when proteins contain pockets in their ground state structures (e.g., the nucleotide-binding active site in myosin motors), achieving specificity remains a central challenge in drug design as many protein families share common structural motifs. Cryptic pockets are cavities absent in ligand-free experimental structures that form due to protein fluctuations in solution. They provide a means to specifically target proteins currently considered undruggable. While cryptic pockets are alluring drug targets, it remains difficult to predict which proteins will form …


A Subset Of Senescent Myofibroblasts Orchestrates Immunosuppression In Pancreatic Cancer., Jad Belle May 2025

A Subset Of Senescent Myofibroblasts Orchestrates Immunosuppression In Pancreatic Cancer., Jad Belle

Arts & Sciences Graduate Student Theses and Dissertations

Pancreatic Ductal Adenocarcinoma (PDAC) is the most lethal solid malignancy with a 12% 5-year survival rate. Most tumors are detected at metastatic stages that are extremely resistant to therapy. PDAC recalcitrance is driven by a unique tumor microenvironment (TME) comprising dense collagenous fibrosis embedded with an abundance of cancer associated fibroblasts (CAFs) and infiltrating leukocytes. Preclinical studies have indicated that PDAC CAFs can have both pro- and anti-tumorigenic effects. This is likely owed to CAF phenotypic heterogeneity which was recently uncovered by single cell transcriptomics. Three major CAF subpopulations have been identified in mouse and human PDAC thus far: myofibroblastic …


Computational Design Of Potent Sirna For Braf Oncogene Silencing For Enhancing Cancer Therapy, Muhammad Hermawan Widyananda, Ricadonna Raissa May 2025

Computational Design Of Potent Sirna For Braf Oncogene Silencing For Enhancing Cancer Therapy, Muhammad Hermawan Widyananda, Ricadonna Raissa

Karbala International Journal of Modern Science

The discovery of oncogenic BRAF mutations has prompted the development of inhibitors, yet resistance remains widespread. A more effective strategy involves targeting BRAF mRNA with siRNA to overcome resistance to BRAF inhibitors. This study aims to design potent siRNA for BRAF oncogene silencing using a computational approach. The full coding sequence of BRAF was retrieved from the NCBI database and potential siRNAs were predicted using the Ui-Tei, Reynolds, and Amarzguioui rules. Identified siRNAs were further analyzed using various prediction systems and parameters, including their interaction with the hAgo2 protein. The results identified that seven siRNAs (siRNA 23, siRNA 24, siRNA …


The Role Of The Cgas-Sting Sensing Pathway In Hiv-1 And Sars-Cov-2 Infections, Jenna Eve Eschbach May 2025

The Role Of The Cgas-Sting Sensing Pathway In Hiv-1 And Sars-Cov-2 Infections, Jenna Eve Eschbach

Arts & Sciences Graduate Student Theses and Dissertations

Human immunodeficiency virus type I (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the causative agents of two unique pandemics. For a successful replication cycle to occur, viruses need to strategically outmaneuver host cell defenses. The innate immune system is the first line of defense against viruses and other pathogens. Host pattern recognition receptors detect viral nucleic acids and initiate signaling cascades that culminate in the expression of interferon (IFN) and transcriptional upregulation of antiviral interferon-stimulated genes (ISGs). This dissertation examines the involvement of the innate immune response during early, post-entry steps of HIV-1 and SARS-CoV-2 infection. During …


Investigating Genetic Regulators Of Crystal Cell Development In Drosophila Melanogaster, Anisa Turaeva, Nyla Walbrook, Andrea Feria, Rebecca Spokony May 2025

Investigating Genetic Regulators Of Crystal Cell Development In Drosophila Melanogaster, Anisa Turaeva, Nyla Walbrook, Andrea Feria, Rebecca Spokony

Publications and Research

In Drosophila melanogaster, hematopoiesis produces three types of blood cells (hemocytes): plasmatocytes, lamellocytes, and crystal cells, all of which provide vital immunological activities. Crystal cells have an especially essential role in melanization, a wound reaction mediated by prophenoloxidase enzymes. This study investigates genetic regulators of crystal cell growth by RNAi-mediated knockdown of five potential genes: ACXA, ACXB, Gp210, CG4390, and Cyp4s3. We used the GAL4/UAS system to selectively silence each gene and quantify crystal cell counts in wandering third instar larvae after heat shock-induced melanization. Our findings indicate that knockdown of ACXA and ACXB resulted in higher crystal cell …


Performative Biomechanics : Evolving Buildings Into Inhabitable Organisms, Josh Lopez May 2025

Performative Biomechanics : Evolving Buildings Into Inhabitable Organisms, Josh Lopez

Bachelor of Architecture Theses - 5th Year

There has always been a connection between biology and architecture. Michael Pawlyn, in Biomimicry in Architecture, coined “biomechanical designs” to describe structural techniques derived from creatures. This study investigates chitin-based creatures. Crustaceans, insects, and microscopic organisms all have exoskeletons in nature. With a focus on crabs, other crustaceans and bugs, this study examines and evaluates the formal characteristics of chitin-based organisms. The architectural creations of OXMAN, NOX, which was founded by Lars Spuybroek; and Lebbeus Woods are among those that are analyzed and studied due to their inspiration from living things. They follow functional effectiveness in nature, which is why …


The Role Of Il-33 In Itch, Anna M. Trier May 2025

The Role Of Il-33 In Itch, Anna M. Trier

Arts & Sciences Graduate Student Theses and Dissertations

Chronic itch is associated with a broad range of medical conditions, from inflammatory skin diseases to cancer and organ dysfunction, and has a lifetime prevalence of up to 20%. Despite being common and debilitating, the cellular and molecular mechanisms that drive chronic itch are just beginning to be elucidated. Thus, therapeutic options are limited. Recent studies have identified that various pro-inflammatory cytokines can directly activate sensory neurons. This has resulted in mounting interest in the therapeutic potential of inhibiting these neuro-immune interactions. IL-33 is constitutively expressed by epithelial cells, which allows for its rapid release upon tissue damage or stress. …


Jarid2-Mediated Reprogramming Of Human Hematopoietic Progenitors For Stem Cell Transplantation, Wentao Han May 2025

Jarid2-Mediated Reprogramming Of Human Hematopoietic Progenitors For Stem Cell Transplantation, Wentao Han

Arts & Sciences Graduate Student Theses and Dissertations

Hematopoietic stem cell transplantation (HSCT) is a well-established treatment for various hematological disorders. Umbilical cord blood (UCB) has emerged as an alternative source of hematopoietic stem and progenitor cells (HSPCs). However, the limited number of functional repopulating cells in UCB units has encouraged researchers to develop methods to expand them ex vivo. Hematopoiesis is strictly regulated by epigenetic modifiers. JARID2 is a co-factor of the Polycomb Repressive Complex 2 (PRC2), which recruits the complex to specific genomic loci and promotes the deposition of Histone 3 lysine 27 trimethylation (H3K27me3), a repressive epigenetic mark that mediates condensed chromatin packing to silence …


Investigating The Roles Of Sox10 And Etv4 In Melanocyte And Melanoma Development, Catherine Marie Newsom-Stewart May 2025

Investigating The Roles Of Sox10 And Etv4 In Melanocyte And Melanoma Development, Catherine Marie Newsom-Stewart

Arts & Sciences Graduate Student Theses and Dissertations

The neural crest is a transient, multipotent cell population unique to vertebrates that gives rise to diverse lineages, including craniofacial cartilage, peripheral neurons, glia, and pigment-producing melanocytes. Proper specification and differentiation of neural crest derivatives are orchestrated by tightly regulated gene regulatory networks, and disruption of these developmental programs can lead to congenital disorders and malignancies. Melanocytes, derived from the neural crest, are best known for their role in skin pigmentation but also contribute to homeostasis and specialized functions in the eye, ear, and heart. These cells produce melanin to protect tissues from ultraviolet radiation and oxidative damage, and they …


Single-Cell Analysis Of Clonal And Transcriptional Dynamics During Direct Reprogramming, Brent Biddy May 2025

Single-Cell Analysis Of Clonal And Transcriptional Dynamics During Direct Reprogramming, Brent Biddy

Arts & Sciences Graduate Student Theses and Dissertations

Direct lineage reprogramming converts one cell type into another, a process characterized by significant heterogeneity. Single-cell genomic techniques have been instrumental in dissecting this variability, yet they often fail to preserve lineage relationships. Here, I present CellTagging, a sequential, combinatorial indexing method that enables the reconstruction of clonal history and gene expression dynamics at single-cell resolution. This facilitates the construction of multi-level lineage trees, providing insights into cellular reprogramming trajectories. We applied CellTagging to investigate direct lineage reprogramming of mouse embryonic fibroblasts into induced endoderm progenitors. Our analysis revealed two distinct reprogramming trajectories: one leading to successful conversion and another …


Characterizing Piezo1 Mechanotransduction In Articular Chondrocytes, Jaquelin Marlen Garcia Castorena May 2025

Characterizing Piezo1 Mechanotransduction In Articular Chondrocytes, Jaquelin Marlen Garcia Castorena

Arts & Sciences Graduate Student Theses and Dissertations

Osteoarthritis (OA) is the most common degenerative joint disease, affecting more than 350 million people worldwide. Along with inflammation and pain, a hallmark of OA is the degradation of articular cartilage (AC), an avascular and aneural tissue that coats and facilitates the bending of diarthrodial joints. AC withstands millions of cyclic mechanical loads annually, and chondrocytes, the only resident cells in the tissue, sense these loads through mechanically gated ion channels, including Transient Receptor Potential Vanilloid 4 (TRPV4), PIEZO1 and PIEZO2. PIEZO1 is a highly expressed calcium ion channel in chondrocytes that can be activated through mechanical loading or chemically …


Effects Of Angptl3 Deficiency On The Regulation Of Hepatic Lipoprotein Production And Lipid Metabolism, Kendall Helene Burks May 2025

Effects Of Angptl3 Deficiency On The Regulation Of Hepatic Lipoprotein Production And Lipid Metabolism, Kendall Helene Burks

Arts & Sciences Graduate Student Theses and Dissertations

Cardiovascular disease is the leading cause of death worldwide. A major treatment goal is to lower plasma lipids, especially low-density lipoprotein cholesterol (LDL), the cardinal risk factor for coronary artery disease (CAD). Patients with familial hypercholesterolemia (FH) experience early-onset CAD due to extremely high LDL. Underdiagnosis and undertreatment of FH are exacerbated by limited therapeutic options. However, one strategy has successfully lowered LDL in FH patients: Inhibition of the hepatically secreted protein Angiopoietin-like protein 3 (ANGPTL3). Despite promising clinical data, the mechanism by which ANGPTL3 inhibition lowers LDL has not been fully described. Although ANGPTL3 has been shown to modulate …


Targeting Nonsense-Mediated Rna Decay In Splicing Factor Mutant Myeloid Malignancies, Claudia Cabrera May 2025

Targeting Nonsense-Mediated Rna Decay In Splicing Factor Mutant Myeloid Malignancies, Claudia Cabrera

Arts & Sciences Graduate Student Theses and Dissertations

Approximately 50% of patients with myelodysplastic syndromes (MDS) (which frequently progresses to secondary acute myeloid leukemia [AML]), 60% of chronic myelomonocytic leukemia (CMML) and 20% of de novo AML harbor heterozygous somatic mutations in spliceosome genes. We and others have shown that mutations in spliceosome genes U2AF1, SF3B1, SRSF2 and ZRSR2 cause alterations in RNA splicing, leading to production of numerous aberrant RNAs. Interestingly, spliceosome mutant cells are more sensitive to genetic alterations or drugs that further perturb RNA splicing, compared to wild-type cells. The sensitivity of spliceosome mutant cells to further perturbations in RNA splicing raises the possibility that …


Functional Diversification Of Rice Ago1 Proteins, Rachel Elie Jouni May 2025

Functional Diversification Of Rice Ago1 Proteins, Rachel Elie Jouni

Arts & Sciences Graduate Student Theses and Dissertations

Global demand for food is outpacing gains from conventional plant breeding. Scientists have turned to molecular crop breeding techniques to increase crop output and mitigate global hunger; however, a common setback in this process is the pleiotropic effects of target genes. We need to develop strategies to specifically modulate desired traits without incurring undesired penalties. Natural evolution frequently balances such tradeoffs through extensive regulation, which we can leverage to produce more specific results. Reproductive development is an important target of breeding efforts due to its direct effect on yield. Rice, a major staple food crop for half the world’s population, …


Understanding Loss Of Beta-Cell Identity And Progression Of Diabetes In Polygenic Mouse Models Of T2dm, Sumitkumar Patel May 2025

Understanding Loss Of Beta-Cell Identity And Progression Of Diabetes In Polygenic Mouse Models Of T2dm, Sumitkumar Patel

Arts & Sciences Graduate Student Theses and Dissertations

Type 2 diabetes (T2DM) is caused by the complex interaction of multiple genes and environmental factors. T2DM is characterized by hyperglycemia, insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While the decline in insulin production and secretion was previously attributed to apoptosis of insulin-producing β-cells, recent studies indicate that β cell apoptosis rates are relatively low in diabetes. In this dissertation, I investigated β-cell failure in diabetes using KK and KKAy mouse models of polygenic T2DM, which spontaneously develop hyperglycemia, glucose intolerance, glucosuria, impaired insulin secretion and insulin resistance. I found that β-cell failure in KK …


Treatment Wastewater Of Oil Refinery By Fe2o3 Nps Produce By The Novel Alishewanella Jeotgali Strain Haq8., Hawraa Qays Al-Assdy, Wijdan Hussein Al-Tamimi, Asia Fadhile Almansoory May 2025

Treatment Wastewater Of Oil Refinery By Fe2o3 Nps Produce By The Novel Alishewanella Jeotgali Strain Haq8., Hawraa Qays Al-Assdy, Wijdan Hussein Al-Tamimi, Asia Fadhile Almansoory

Karbala International Journal of Modern Science

Metal oxide nanoparticles like iron oxide (Fe2O3) exhibit strong reactivity and photolytic features in wastewater treatment and serve as an effective adsorbent for water purification due to its substantial surface area and affinity for different functionalized groups. Iron oxide nanoparticles) IONPs) are currently applied to treat oil-contaminated water. Fe₂O₃NPs were produced using an extracellular approach utilizing the Alishewanella jeotgali strain HAQ8. IONPs were characterized using UV-vis, FT-IR, XRD, AFM, SEM-EDX, and Zeta potential. λ max for the synthesized nanoparticles observed at (358) nm. The bands at 485 cm⁻¹ in the FT-IR spectrum confirmed the formation of …


Mechanisms Of Protective Humoral Immunity And Pathogenesis In Alphavirus Infection, Natasha Monir Kafai May 2025

Mechanisms Of Protective Humoral Immunity And Pathogenesis In Alphavirus Infection, Natasha Monir Kafai

Arts & Sciences Graduate Student Theses and Dissertations

Alphaviruses are enveloped, mosquito-transmitted, positive-sense RNA viruses of the Togaviridae family classified into Old and New World groups based on endemic regions and human disease characteristics. Old World alphaviruses, including chikungunya virus preferentially cause arthritogenic disease, whereas New World viruses like Venezuelan equine encephalitis virus (VEEV), Eastern equine encephalitis virus (EEEV), and Western equine encephalitis virus (WEEV) can cause neurological disease. Since the 1920s, VEEV has been responsible for major periodic outbreaks affecting hundreds of thousands of humans and equines in South and Central America. Expansion of mosquito vectors raises concern for possible VEEV reemergence. In addition, VEEV is a …


Examing The Role Of Complement Signaling In Viral Neuroinflammatory Responses, Marlene Kanmogne May 2025

Examing The Role Of Complement Signaling In Viral Neuroinflammatory Responses, Marlene Kanmogne

Arts & Sciences Graduate Student Theses and Dissertations

The complement system is an ancient pathway that serves dual roles as a key regulator of neuroinflammation and a critical regulator of neural networks. Few studies have addressed how these two pathways may interact during infection of the central nervous system. While some components of complement are expressed in the healthy developing brain, complement component 3a receptor (C3aR) is a G protein coupled receptor that is expressed by astrocytes, microglia and infiltrating immune cells during inflammatory states. We previously found that C3aR is required for engulfment of synaptic material by activated microglia during neuroinvasive viral infection. Here, we used a …


Proteogenomic Analysis To Inform Causal Gene Prioritization For Human Disease, Daniel Western May 2025

Proteogenomic Analysis To Inform Causal Gene Prioritization For Human Disease, Daniel Western

Arts & Sciences Graduate Student Theses and Dissertations

Genome-wide association studies (GWAS) have been key in expanding our understanding of the genetic contributions to common diseases. However, these genetic associations frequently fail to clarify causal disease mechanisms, as they often fall in non-coding regions and are difficult to interpret. One solution is to perform a GWAS for the levels of a cellular trait, known as quantitative trait locus (QTL) mapping. Through methods such as colocalization, Mendelian Randomization, and transcriptome/proteome-wide association studies, the QTL variants can be compared to disease GWAS, identifying shared variation between cellular and disease traits. We can then prioritize cellular traits as potential causative, targetable …


Mutant-Specific Analysis Of Tumor Cell Heterogeneity In Glioblastoma, Patrick Desouza May 2025

Mutant-Specific Analysis Of Tumor Cell Heterogeneity In Glioblastoma, Patrick Desouza

Arts & Sciences Graduate Student Theses and Dissertations

Glioblastoma (GBM) is an aggressive brain tumor driven by the interplay between tumor cell-intrinsic and -extrinsic heterogeneity, enabling rapid evolution. To investigate how canonical GBM mutations promote functional plasticity, we developed an isogenic human neural stem cell (NSC) model of GBM by sequential addition of TERT promoter, TP53, and PDGFRA point mutations. TP53 loss-of-function increased TERT expression during serial mutagenesis, but only triple mutant NSCs reliably formed lethal brain tumors in vivo that recapitulate GBM. Tumor cell evolution triggered stress-related metabolic changes and transitioned toward a neuronal progenitor network driven by transcription factor INSM1. INSM1 is highly expressed in human …


Acquisition Algorithms For Protein Mass Spectrometry And Their Application To Clinical Proteomics, Nathan Wamsley May 2025

Acquisition Algorithms For Protein Mass Spectrometry And Their Application To Clinical Proteomics, Nathan Wamsley

Arts & Sciences Graduate Student Theses and Dissertations

Bottom-up protein mass spectrometry aims for the identification and quantification of protein species by proxy of their proteolytic peptides. This dissertation presents methodological advances in three areas of protein mass spectrometry: acquisition methods, clinical appli- cations, and data analysis algorithms. The second chapter presents an optimized internal standard-triggered parallel reaction monitoring (OIS-PRM) method and demonstrates its application to study prognostic biomarkers in head and neck squamous cell carcinoma (HN- SCC). OIS-PRM uses intelligent scan scheduling and real-time monitoring of peptide elution profiles to reduce cycle-times and improve quantitative precision and accuracy. The assay measured NRF2 activation in both cell lines …


Endemism Shapes Viral Ecology And Evolution In Globally Distributed Hydrothermal Vent Ecosystems, Marguerite V. Langwig, Faith Koester, Cody Martin, Zhichao Zhou, Samantha B. Joye, Anna-Louise Reysenbach, Karthik Anantharaman May 2025

Endemism Shapes Viral Ecology And Evolution In Globally Distributed Hydrothermal Vent Ecosystems, Marguerite V. Langwig, Faith Koester, Cody Martin, Zhichao Zhou, Samantha B. Joye, Anna-Louise Reysenbach, Karthik Anantharaman

Biology Faculty Publications and Presentations

Viruses are ubiquitous in deep-sea hydrothermal vents, where they influence microbial communities and biogeochemistry. Yet, viral ecology and evolution remain understudied in these environments. Here, we identify 49,962 viruses from 52 globally distributed hydrothermal vent samples (10 plume, 40 deposit, and 2 diffuse flow metagenomes), and reconstruct 5708 viral metagenome-assembled genomes, the majority of which were bacteriophages. Hydrothermal viruses were largely endemic, however, some viruses were shared between geographically separated vents, predominantly between the Lau Basin and Brothers Volcano in the Pacific Ocean. Geographically distant viruses shared proteins related to core functions such as structural proteins, and rarely, proteins of …


Genomic Structure Among Populations Of A Regionally Rare Perennial Plant Indicates The Need For Reevaluation Of Management Units, Cheyenne Moore, Angela J. Mcdonnell, Scott Schuette, Christopher T. Martine May 2025

Genomic Structure Among Populations Of A Regionally Rare Perennial Plant Indicates The Need For Reevaluation Of Management Units, Cheyenne Moore, Angela J. Mcdonnell, Scott Schuette, Christopher T. Martine

Faculty Journal Articles

Conservation of rare species often relies on the delineation of management units and genomic tools can now be applied for this purpose. However, this is not as common on a local scale, where populations are often small and fragmented, despite the utility of informing conservation and management practice at the regional level. We use a genotyping by sequencing (GBS) approach to assess the perennial riparian plant species Baptisia australis (Fabaceae) in Pennsylvania, where the taxon is at the edge of its natural distribution and considered threatened. In this system, we investigate whether sampled subpopulations exhibit genetic structure. We find that …


Parsing Heterogeneity In Depression, Kayla Hannon May 2025

Parsing Heterogeneity In Depression, Kayla Hannon

Arts & Sciences Graduate Student Theses and Dissertations

Depression is a highly prevalent mental health disorder that often requires treatment. While current treatments are effective for a large portion of patients generally, the exact medication that works for any specific person is unclear, leading to large delays in symptom remittance if at all. This hurdle has motivated substantial efforts to identify markers of depression that might predict treatment outcomes. However, large sources of heterogeneity in depression have stymied progress on identifying robust and replicable neuroimaging markers. Parsing this heterogeneity is crucial but mired with challenges. My dissertation work has elucidated several key barriers in parsing the heterogeneity of …


Exploring Mobility: Phylogenetic And Structural Analysis Of The Intein In The Helicase Of Mycobacteriophage Alice, Sandra Xu May 2025

Exploring Mobility: Phylogenetic And Structural Analysis Of The Intein In The Helicase Of Mycobacteriophage Alice, Sandra Xu

Honors Scholar Theses

This paper investigates the intein insertion in the DNA helicase gene Alice_175 of the Mycobacterium phage Alice, exploring its evolutionary significance and potential propagation mechanisms. Using phylogenetic analysis, there is evidence for gene transfer as a driving force in intein dissemination in phage and bacterial genomes. Structural predictions of the Alice_175 intein that were generated through AlphaFold2 as well as a phylogeny generated using SeaView infer a timeline of the intein's invasion and reveal key features that may influence protein functionality and host adaptation. Additionally, protein database searches suggest that intein mobility in this gene may not rely on prophages, …


Role Of The Small Intestinal Microbiota In The Pathogenesis Of Environmental Enteric Dysfunction In Undernourished Children And Mothers, Clara Kao May 2025

Role Of The Small Intestinal Microbiota In The Pathogenesis Of Environmental Enteric Dysfunction In Undernourished Children And Mothers, Clara Kao

Arts & Sciences Graduate Student Theses and Dissertations

Undernutrition in women and its propagation in their children remains a major global health challenge. Worldwide, one in five children under five years of age manifests undernutrition as impaired linear growth, or stunting. Stunting, defined as having a length-for-age z-score (LAZ) <-2, is associated with poor developmental outcomes, including impaired neurodevelopment and immune responses. Furthermore, stunting and its long-term sequelae persist across generations, contributing to an intergenerational cycle of undernutrition. Existing nutritional interventions fail to substantially improve stunting, highlighting the need to (i) better understand other factors contributing to stunting and (ii) focus clinical efforts towards treating maternal undernutrition. Environmental enteric dysfunction (EED) is a subclinical inflammatory enteropathy of the small intestine proposed to contribute to stunting. EED is diagnosed histologically by blunted intestinal villi, epithelial barrier disruption and an immunoinflammatory infiltrate in the lamina propria. However, the pathophysiology of EED remains poorly defined. Furthermore, the small intestinal microbiota remains understudied due to difficulties in sampling. Evidence that the small intestinal microbiota contributes to EED pathogenesis comes in part from our collaborative work with colleagues at icddr,b (the International Centre for Diarrhoeal Disease Research, Bangladesh) who oversaw the Bangladesh EED (BEED) study. In this study children, aged 12-18 months residing in an urban slum in the Mirpur district of Dhaka who failed a nutritional intervention for their stunting, underwent esophago-gastroduodenoscopy (EGD) to obtain duodenal mucosal biopsies, aspirates of duodenal luminal fluid and plasma samples. A set of 14 bacteria taxa (defined by 16S rRNA amplicon sequencing) were identified in the duodenal microbiota of >80% of children with EED. Moreover, the absolute abundances of these ‘core taxa’ were positively correlated with duodenal mucosal and systemic inflammation in study participants and negatively correlated with linear growth. Our lab showed that introduction of a consortium of bacteria cultured from these duodenal aspirates, including these core taxa, produced small intestinal inflammation in young adult gnotobiotic, providing …


Functional Morphology Of The Primate Knee And Its Implications For Hominin Bipedal Mechanics, Catherine K. Miller May 2025

Functional Morphology Of The Primate Knee And Its Implications For Hominin Bipedal Mechanics, Catherine K. Miller

Dartmouth College Ph.D Dissertations

Bipedal locomotion is central to the human condition, having shaped our evolutionary trajectory since its early emergence in the hominin lineage. Despite its importance, key questions remain about its origins and evolutionary trajectory. While many studies have focused on locomotor-related anatomies, comparatively less attention has been paid to the knee joint – a structure critical to the primate locomotor repertoire. This dissertation aims to clarify the form-function relationship of the knee in extant primates to better infer the locomotor behaviors of Miocene hominoids and Plio-Pleistocene hominins. To address these questions, this research employs a multifaceted analytical approach, integrating linear measurements, …


Impacts Of German Yellowjacket (Vespula Germanica) Removal On Pollinator Communities In Western New York, Jonathan M. Promowicz May 2025

Impacts Of German Yellowjacket (Vespula Germanica) Removal On Pollinator Communities In Western New York, Jonathan M. Promowicz

Biology Theses

Invasive social insects can restructure native arthropod communities through predation and competition. Vespula germanica (German yellowjacket) is a globally invasive wasp species that dominates vespid assemblages across urban and suburban landscapes. This study tested the hypothesis that reducing V. germanica using protein-based fipronil baits would increase native pollinator abundance, species richness and native vespid abundance. Vespula germanica was experimentally suppressed at suburban and urban sites. Pollinator abundance and richness increased with V. germanica baiting. Native vespids had mixed results from baiting with suburban sites increasing in overall abundance and urban sites decreasing. These results indicate that suppressing dominant invasive wasps …


The Anorexigenic Peptide Nesfatin-1 Dampens The B Cell Response To Receptor-Mediated Stimulation Through Inhibition Of Nf-Jb Signaling, Tara L. Steffen, Joshua D. Stafford, Colleen R. Bocke, Willis K. Samson, Gina L.C. Yosten May 2025

The Anorexigenic Peptide Nesfatin-1 Dampens The B Cell Response To Receptor-Mediated Stimulation Through Inhibition Of Nf-Jb Signaling, Tara L. Steffen, Joshua D. Stafford, Colleen R. Bocke, Willis K. Samson, Gina L.C. Yosten

Biological Sciences Faculty Research & Creative Works

Nesfatin-1, a posttranslational product of the protein encoded by the nucleobindin 2 gene (NUCB2), was functionally identified as an appetite regulatory molecule in rat hypothalamic nuclei. In the years following the discovery, those findings have been corroborated and expanded upon, and we now know that nesfatin-1 is expressed throughout peripheral tissues and exerts physiological effects beyond feeding control. Literature indicates that adipose tissue is one of the peripheral sources of NUCB2/nesfatin-1, and in this setting, it has anti-inflammatory effects that have recently been implicated in regulating chronic inflammation associated with diet-induced obesity. Currently, there are gaps in our understanding of …