Digital Commons Network^™

Time Flies: An Analysis Of Circadian Impact Upon Cell Cycle Regulation Using Boolean Modeling And A Developmental Drosophila Model, Emma Elizabeth Davidson

Senior Independent Study Theses

No abstract provided.

Highlights Generation For Tennis Matches Using Computer Vision, Natural Language Processing And Audio Analysis, Alon Liberman

Senior Independent Study Theses

This project uses computer vision, natural language processing and audio analysis to automatize the highlights generation task for tennis matches. Computer vision techniques such as camera shot detection, hough transform and neural networks are used to extract the time intervals of the points. To detect the best points, three approaches are used. Point length suggests which points correspond to rallies and aces. The audio waves are analyzed to search for the highest audio peaks, which indicate the moments where the crowd cheers the most. Sentiment analysis, a natural language processing technique, is used to look for points where the commentators …

Environmental Socialization In College: A Survey Research And Network Analysis Of Changes In Climate-Conscious Concerns And Behaviors, Bijeta Lamichhane

Senior Independent Study Theses

Studies have established that socialization takes place in different stages of life. This study explores how political socialization occurs at The College of Wooster by examining changes in students' political identities as well as their perceptions towards a politicized issue, that is, climate change. These shifts in beliefs and concerns among students were evaluated by implementing quantitative research tools present in the Statistical Package for Social Sciences (SPSS) and constructing a similarity network using Gephi to explore similarities across students at this institution. The results revealed that students have become more liberal after joining this college. The study also found …

Microplastics As Carrier Of Pahs Released From Oil Spills: Measuring Ingestion And Bioaccumulation Rates In Copepods, Manasi Desai

Senior Independent Study Theses

Microplastics (MP; plastics < 5mm) are a growing problem in the marine environment due to a large influx of plastics entering the marine environment through rivers, wastewater and litter from land. MP are known to adsorb nonpolar compounds in the water including polycyclic aromatic hydrocarbons (PAHs) released from oil spills. In this study, I quantified the ingestion rates of a marine copepod (Calanus finmarchicus) on clean polystyrene MP beads (12 um) and phenanthrene loaded MP beads (0.8 pg PAH pellet -1). I measured the phenanthrene load in copepods ingesting phenanthrene sorbed MPs and copepods exposed to phenanthrene only to measure the role of MP as a vector for PAHs into marine food webs. Additionally, I examined the fecal pellets to check the presence of MPs and if phenanthrene was still adsorbed to them. The results showed that microplastics do not act as vectors as there was no significant difference between the body load of phenanthrene in copepods from ingestion of PAH sorbed MPs and the body load from passive uptake of phenanthrene in solution. Copepods ate significantly lower phenanthrene loaded MP (1.81 x 104 beads cop-1 day-1) than microplastics only (2.67 x 104 beads cop-1 day-1) suggesting that copepods can reject particles based on chemical content. Accumulation of phenanthrene within the copepods (GC-MS analysis) showed individual copepods can accumulate between 3.48 to 4.11 ng of PAH which potentially can biomagnify in the marine food web upon predation. Fecal pellet analysis showed that an average of 2013 MP beads are present with a mean phenanthrene load of 0.15 pg bead-1. For the social science research, I conducted a literature review examining the current Indian plastic waste management strategies, legislations and its implementation. My results find that the Indian government over the years has progressively enacted and amended its policies to try to keep pace with the issue of plastic pollution. However, key challenges in the implementation such as poor enforcement, inadequate training for recycling lack of plastic alternatives and proper waste disposal infrastructure all contribute to the unsuccessful management of waste. Usage of plastic in road construction has shown to be a viable option in reducing plastic waste in India and also improving road conditions.

Cdc20 Regulates Sensitivity To Chemotherapy And Radiation In Glioblastoma Stem Cells, Diane D. Mao, Ryan T. Cleary, Amit Gujar, Tatenda Mahlokozera, Albert H. Kim

2020-Current year OA Pubs

Glioblastoma stem cells (GSCs) are an important subpopulation in glioblastoma, implicated in tumor growth, tumor recurrence, and radiation resistance. Understanding the cellular mechanisms for chemo- and radiation resistance could lead to the development of new therapeutic strategies. Here, we demonstrate that CDC20 promotes resistance to chemotherapy and radiation therapy. CDC20 knockdown does not increase TMZ- and radiation-induced DNA damage, or alter DNA damage repair, but rather promotes cell death through accumulation of the pro-apoptotic protein, Bim. Our results identify a CDC20 signaling pathway that regulates chemo- and radiosensitivity in GSCs, with the potential for CDC20-targeted therapeutic strategies in the treatment …

Comparative Analysis Of Dcas9-Vp64 Variants And Multiplexed Guide Rnas Mediating Crispr Activation, Kohei Omachi, Jeffrey H. Miner

2020-Current year OA Pubs

CRISPR/Cas9-mediated transcriptional activation (CRISPRa) is a powerful tool for investigating complex biological phenomena. Although CRISPRa approaches based on the VP64 transcriptional activator have been widely studied in both cultured cells and in animal models and exhibit great versatility for various cell types and developmental stages in vivo, different dCas9-VP64 versions have not been rigorously compared. Here, we compared different dCas9-VP64 constructs in identical contexts, including the cell lines used and the transfection conditions, for their ability to activate endogenous and exogenous genes. Moreover, we investigated the optimal approach for VP64 addition to VP64- and p300-based constructs. We found that MS2-MCP-scaffolded …

Preeclampsia Is Associated With Reduced Isg15 Levels Impairing Extravillous Trophoblast Invasion, Asli Ozmen, Anthony O Odibo, Et Al

2020-Current year OA Pubs

Among several interleukin (IL)-6 family members, only IL-6 and IL-11 require a gp130 protein homodimer for intracellular signaling due to lack of intracellular signaling domain in the IL-6 receptor (IL-6R) and IL-11R. We previously reported enhanced decidual IL-6 and IL-11 levels at the maternal-fetal interface with significantly higher peri-membranous IL-6 immunostaining in adjacent interstitial trophoblasts in preeclampsia (PE) vs. gestational age (GA)-matched controls. This led us to hypothesize that competitive binding of these cytokines to the gp130 impairs extravillous trophoblast (EVT) differentiation, proliferation and/or invasion. Using global microarray analysis, the current study identified inhibition of interferon-stimulated gene 15 (

Glutathione S-Transferase Alpha 4 Promotes Proliferation And Chemoresistance In Colorectal Cancer Cells, Zhanhu Zhang, Lili Xu, Lin Huang, Tianqi Li, Jane Y Wang, Chunhua Ma, Xiaoyun Bian, Xiaoyan Ren, Haibo Li, Xingmin Wang

2020-Current year OA Pubs

Glutathione

Efficient T Cell Migration And Activation Require L-Plastin, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

Rapid re-organization of the actin cytoskeleton supports T-cell trafficking towards immune sites and interaction with antigen presenting cells (APCs). F-actin rearrangement enables T-cell trafficking by stabilizing adhesion to vascular endothelial cells and promoting transendothelial migration. T-cell/APC immune synapse (IS) maturation also relies upon f-actin-anchored LFA-1:ICAM-1 ligation. Therefore, efficient T-cell responses require tight regulation of f-actin dynamics. In this review, we summarize how the actin-bundling protein L-plastin (LPL) regulates T-cell activation and migration. LPL enhances f-actin polymerization and also directly binds to the β2 chain of the integrin LFA-1 to support intercellular adhesion and IS formation in human and murine T …

Checkpoint Blockade-Induced Cd8+ T Cell Differentiation In Head And Neck Cancer Responders, Liye Zhou, Paul Zolkind, Obi Griffith, Et Al

2020-Current year OA Pubs

BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined.

METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models.

RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. …

Subtyping Of Common Complex Diseases And Disorders By Integrating Heterogeneous Data. Identifying Clusters Among Women With Lower Urinary Tract Symptoms In The Lurn Study, Victor P. Andreev, H Henry Lai, Et Al

2020-Current year OA Pubs

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data …

A Polygenic Risk Score Based On A Cardioembolic Stroke Multitrait Analysis Improves A Clinical Prediction Model For This Stroke Subtype, Jara Cárcel-Márquez, Laura Ibañez, Laura Heitsch, Rajat Dhar, Carlos Cruchaga, Jin-Moo Lee, Et Al

2020-Current year OA Pubs

Background: Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification.

Methods: Multitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (

Results: We found and replicated …

Where Do T Cell Subsets Stand In Sars-Cov-2 Infection: An Update, Mohammad Tarique, Mohd Suhail, Huma Naz, Naoshad Muhammad, Shams Tabrez, Torki A Zughaibi, Adel M Abuzenadah, Anwar M Hashem, Hari Shankar, Chaman Saini, Alpana Sharma

2020-Current year OA Pubs

An outbreak of coronavirus disease 2019 (COVID-19) emerged in China in December 2019 and spread so rapidly all around the globe. It's continued and spreading more dangerously in India and Brazil with higher mortality rate. Understanding of the pathophysiology of COVID-19 depends on unraveling of interactional mechanism of SARS-CoV-2 and human immune response. The immune response is a complex process, which can be better understood by understanding the immunological response and pathological mechanisms of COVID-19, which will provide new treatments, increase treatment efficacy, and decrease mortality associated with the disease. In this review we present a amalgamate viewpoint based on …

Advances In Understanding Interferon-Mediated Immune Responses To Enteric Viruses In Intestinal Organoids, Lila S Nolan, Megan T Baldridge

2020-Current year OA Pubs

Interferons (IFN) are antiviral cytokines with critical roles in regulating pathogens at epithelial barriers, but their capacity to restrict human enteric viruses has been incompletely characterized in part due to challenges in cultivating some viruses

A Recombinant Murine-Like Rotavirus With Nano-Luciferase Expression Reveals Tissue Tropism, Replication Dynamics, And Virus Transmission, Yinxing Zhu, Liliana Sánchez-Tacuba, Gaopeng Hou, Takahiro Kawagishi, Ningguo Feng, Harry B Greenberg, Siyuan Ding

2020-Current year OA Pubs

Rotaviruses (RVs) are one of the main causes of severe gastroenteritis, diarrhea, and death in children and young animals. While suckling mice prove to be highly useful small animal models of RV infection and pathogenesis, direct visualization tools are lacking to track the temporal dynamics of RV replication and transmissibility

Bsl2-Compliant Lethal Mouse Model Of Sars-Cov-2 And Variants Of Concern To Evaluate Therapeutics Targeting The Spike Protein, Mohanraj Manangeeswaran, Derek D C Ireland, Seth G Thacker, Ha-Na Lee, Logan Kelley-Baker, Aaron P Lewkowicz, Paul W Rothlauf, Marjorie Cornejo Pontelli, Louis-Marie Bloyet, Michael A Eckhaus, Mirian I Mendoza, Sean Whelan, Daniela Verthelyi

2020-Current year OA Pubs

Since first reported in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly acquiring mutations, particularly in the spike protein, that can modulate pathogenicity, transmission and antibody evasion leading to successive waves of COVID19 infections despite an unprecedented mass vaccination necessitating continuous adaptation of therapeutics. Small animal models can facilitate understanding host-pathogen interactions, target selection for therapeutic drugs, and vaccine development, but availability and cost of studies in BSL3 facilities hinder progress. To generate a BSL2-compatible

At-Home Blood Collection And Stabilization In High Temperature Climates Using Home Rna, Lauren G Brown, Amanda J Haack, Dakota S Kennedy, Karen N Adams, Jennifer E Stolarczuk, Meg G Takezawa, Erwin Berthier, Sanitta Thongpang, Fang Yun Lim, Damien Chaussabel, Mathieu Garand, Ashleigh B Theberge

2020-Current year OA Pubs

Expanding whole blood sample collection for transcriptome analysis beyond traditional phlebotomy clinics will open new frontiers for remote immune research and telemedicine. Determining the stability of RNA in blood samples exposed to high ambient temperatures (>30°C) is necessary for deploying home-sampling in settings with elevated temperatures (e.g., studying physiological response to natural disasters that occur in warm locations or in the summer). Recently, we have developed

Socioecological Model-Based Design And Implementation Principles Of Lower Limb Preservation Programs As Partners For Limb-Loss Rehabilitation Programs- A Mini-Review, Vipul Khetarpaul, John P Kirby, Patrick Geraghty, John Felder, Prateek Grover

2020-Current year OA Pubs

People with lower limb loss, especially of dysvascular etiology, are at substantial risk for both ipsilateral and contralateral reamputation. Additionally, while not as well documented for reamputation, there is recognition that amputation incidence is influenced by not only sociodemographic factors such as sex, race, socioeconomic status, but also by system factors such as service access. A systems strategy to address this disparity within the field of limb-loss rehabilitation is for Limb-loss Rehabilitation Programs (LRP) to partner with medical specialists, mental health professionals, and Limb Preservation Programs (LPP) to provide comprehensive limb care. While LPPs exist around the nation, design principles …

Use Of Leishmania Major Parasites Expressing A Recombinant Trypanosoma Cruzi Antigen As Live Vaccines Against Chagas Disease, Catherine W Cai, Anne O'Shea, Christopher S Eickhoff, Hongjie Guo, Warren G Lewis, Stephen M Beverley, Daniel F Hoft

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We generated recombinant

RESULTS: We demonstrate that mice inoculated with these recombinant TS-expressing

DISCUSSION: Altogether, these data indicate that

The Future Of Ad Clinical Trials With The Advent Of Anti-Amyloid Therapies: An Ctad Task Force Report, J Delrieu, R J Bateman, J Touchon, M Sabbagh, J Cummings

2020-Current year OA Pubs

BACKGROUND: Aducanumab (ADUHELMTM) was approved for the treatment of Alzheimer's disease (AD) in the US. This approval was supported by an effect on the cerebral amyloid plaque load and evidence of cognitive efficacy to be confirmed in post-marketing trials. Other anti-amyloid antibodies are under investigation in phase III (donanemab, lecanemab, gantenerumab) and have shown preliminary evidence of a cognitive benefit in phase II trials. Although these agents target a small segment of patients with mild cognitive impairment due to AD or mild AD dementia, their advent will change the design of future clinical trials both for anti-amyloid and non-amyloid drugs. …

Fluorescence Imaging Of Beta Cell Primary Cilia, Zipeng A Li, Jung Hoon Cho, Louis G Woodhams, Jing W Hughes

2020-Current year OA Pubs

Primary cilia are slender cell-surface organelles that project into the intercellular space. In pancreatic beta cells, primary cilia coordinate a variety of cell responses including GPCR signaling, calcium influx, and insulin secretion, along with likely many underappreciated roles in islet development and differentiation. To study cilia function in islet biology, direct visualization of primary cilia by microscopic methods is often a necessary first step. Ciliary abundance, distribution, and morphology are heterogeneous among islet cells and are best visualized by fluorescence microscopy, the tools for which are readily accessible to most researchers. Here we present a collection of fluorescence imaging methods …

Weakly Activated Core Neuroinflammation Pathways Were Identified As A Central Signaling Mechanism Contributing To The Chronic Neurodegeneration In Alzheimer's Disease, Fuhai Li, Abdallah M Eteleeb, William Buchser, Christopher Sohn, Guoqiao Wang, Chengjie Xiong, Philip R Payne, Eric Mcdade, Celeste M Karch, Oscar Harari, Carlos Cruchaga

2020-Current year OA Pubs

OBJECTIVES: Neuroinflammation signaling has been identified as an important hallmark of Alzheimer's disease (AD) in addition to amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs). However, the molecular mechanisms and biological processes of neuroinflammation remain unclear and have not well delineated using transcriptomics data available. Our objectives are to uncover the core neuroinflammation signaling pathways in AD using integrative network analysis on the transcriptomics data.

MATERIALS AND METHODS: From a novel perspective, i.e., investigating weakly activated molecular signals (rather than the strongly activated molecular signals), we developed integrative and systems biology network analysis to uncover potential core neuroinflammation signaling targets …

Actin Capping Protein Regulates Postsynaptic Spine Development Through Cpi-Motif Interactions, Kenneth R Myers, Yanjie Fan, Patrick Mcconnell, John A Cooper, James Q Zheng

2020-Current year OA Pubs

Dendritic spines are small actin-rich protrusions essential for the formation of functional circuits in the mammalian brain. During development, spines begin as dynamic filopodia-like protrusions that are then replaced by relatively stable spines containing an expanded head. Remodeling of the actin cytoskeleton plays a key role in the formation and modification of spine morphology, however many of the underlying regulatory mechanisms remain unclear. Capping protein (CP) is a major actin regulating protein that caps the barbed ends of actin filaments, and promotes the formation of dense branched actin networks. Knockdown of CP impairs the formation of mature spines, leading to …

Abnormal Synergies And Associated Reactions Post-Hemiparetic Stroke Reflect Muscle Activation Patterns Of Brainstem Motor Pathways, Laura M Mcpherson, Julius P A Dewald

2020-Current year OA Pubs

Individuals with moderate-to-severe post-stroke hemiparesis cannot control proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called flexion and extension synergies. Accumulating evidence indicates that these synergies emerge because of upregulation of diffusely projecting brainstem motor pathways following stroke-induced damage to corticofugal pathways. During our recent work on differences in synergy expression among proximal and distal joints, we serendipitously observed some notable characteristics of synergy-driven muscle activation. It seemed that: paretic wrist/finger muscles were activated maximally during contractions of muscles at a different joint; differences in the magnitude of synergy expression occurred when …

Totally Percutaneous Endovascular Repair For Ruptured Abdominal Aortic Aneurysms, Shirli Tay, Mohamed S Zaghloul, Mehreen Shafqat, Chao Yang, Kshitij A Desai, Gayan De Silva, Luis A Sanchez, Mohamed A Zayed

2020-Current year OA Pubs

PURPOSE: The PEVAR Trial demonstrated that compared to open femoral exposure, elective percutaneous endovascular AAA repair (ePEVAR) is associated with decreased perioperative morbidity and access site complications. We hypothesized that PEVAR for ruptured AAA (rPEVAR) may also improve perioperative morbidity compared to open femoral exposure (rEVAR). There are currently no reports that evaluate the utility and outcomes of rPEVAR.

MATERIALS AND METHODS: From 2015 to 2021, all patients who underwent an endovascular repair of a ruptured AAA at a single institution were included in the study and grouped into rPEVAR and rEVAR. Demographics, procedural details (successful preclose technique, conversion to …

Intraocular Human Cytomegaloviruses Of Ocular Diseases Are Distinct From Those Of Viremia And Are Capable Of Escaping From Innate And Adaptive Immunity By Exploiting Hla-E-Mediated Peripheral And Central Tolerance, Mariko Shirane, Michael Paley, Wayne M Yokoyama, Et Al.

2020-Current year OA Pubs

Human cytomegalovirus (HCMV) infections develop into CMV diseases that result in various forms of manifestations in local organs. CMV-retinitis is a form of CMV disease that develops in immunocompromised hosts with CMV-viremia after viruses in the peripheral circulation have entered the eye. In the HCMV genome, extensive diversification of the UL40 gene has produced peptide sequences that modulate NK cell effector functions when loaded onto HLA-E and are subsequently recognized by the NKG2A and NKG2C receptors. Notably, some HCMV strains carry UL40 genes that encode peptide sequences identical to the signal peptide sequences of specific HLA-A and HLA-C allotypes, which …

Expansion Of A Novel Population Of Nk Cells With Low Ribosome Expression In Juvenile Dermatomyositis, Kinsey A Hilliard, Allison A Throm, Jeanette T Pingel, Nermina Saucier, Hani S Zaher, Anthony R French

2020-Current year OA Pubs

Juvenile dermatomyositis (JDM) is a pediatric autoimmune disease associated with characteristic rash and proximal muscle weakness. To gain insight into differential lymphocyte gene expression in JDM, peripheral blood mononuclear cells from 4 new-onset JDM patients and 4 healthy controls were sorted into highly enriched lymphocyte populations for RNAseq analysis. NK cells from JDM patients had substantially greater differentially expressed genes (273) than T (57) and B (33) cells. Upregulated genes were associated with the innate immune response and cell cycle, while downregulated genes were associated with decreased ribosomal RNA. Suppressed ribosomal RNA in JDM NK cells was validated by measuring …

Correlating Electroconvulsive Therapy Response To Electroencephalographic Markers: Study Protocol, Subha Subramanian, Alyssa K Labonte, Thomas Nguyen, Anhthi H Luong, Orlandrea Hyche, S Kendall Smith, R Edward Hogan, Nuri B Farber, Ben Julian A Palanca, Mohammadmehdi Kafashan, Cet-Rem Study Group

2020-Current year OA Pubs

INTRODUCTION: Electroconvulsive therapy (ECT) is an effective intervention for patients with major depressive disorder (MDD). Despite longstanding use, the underlying mechanisms of ECT are unknown, and there are no objective prognostic biomarkers that are routinely used for ECT response. Two electroencephalographic (EEG) markers, sleep slow waves and sleep spindles, could address these needs. Both sleep microstructure EEG markers are associated with synaptic plasticity, implicated in memory consolidation, and have reduced expression in depressed individuals. We hypothesize that ECT alleviates depression through enhanced expression of sleep slow waves and sleep spindles, thereby facilitating synaptic reconfiguration in pathologic neural circuits.

METHODS: Correlating …

Control Of Aging By The Renin-Angiotensin System: A Review Of C. Elegans, Drosophila, And Mammals, Brian M Egan, Andrea Scharf, Franziska Pohl, Kerry Kornfeld

2020-Current year OA Pubs

The free-living, non-parasitic nematode

Implicating Genes, Pleiotropy, And Sexual Dimorphism At Blood Lipid Loci Through Multi-Ancestry Meta-Analysis, Stavroula Kanoni, Adam E. Locke, E Warwick Daw, Mary F. Feitosa, Mary K. Wojczynski, Bernhard Banas, Carsten A. Boger, Bettina Jung, D C. Rao, Michael A. Province, Et Al.

2020-Current year OA Pubs

No abstract provided.