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Articles 1 - 8 of 8
Full-Text Articles in Life Sciences
Investigating The Mechanisms Of Surface Sensing Using Motility Appendages By Pseudomonas Aeruginosa Pa14, Christopher James Geiger
Investigating The Mechanisms Of Surface Sensing Using Motility Appendages By Pseudomonas Aeruginosa Pa14, Christopher James Geiger
Dartmouth College Ph.D Dissertations
Biofilms are surfaced attached communities of cells encased in an extracellular matrix. The transition from free-swimming planktonic cells to a surface attached biofilm begins with cellular changes that occur after surface contact. This process is known as "surface sensing" and the opportunistic pathogen Pseudomonas aeruginosa PA14 uses its two motility appendages, type IV pili (T4P) and a single, polar flagellum to sense and traverse surfaces. The first cellular changes to occur within this organism upon surface contact is an increase in the second messengers cAMP and cdi- GMP. While the genes involved in surface sensing by P. aeruginosa are known, …
Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang
Dartmouth College Ph.D Dissertations
DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …
Tracing Evolution Of Gene Transfer Agents Using Comparative Genomics, Roman Kogay
Tracing Evolution Of Gene Transfer Agents Using Comparative Genomics, Roman Kogay
Dartmouth College Ph.D Dissertations
The accumulating evidence suggest that viruses and their components can be domesticated by their hosts, equipping them with convenient molecular toolkits for various functions. One of such domesticated system is Gene Transfer Agents (GTAs) that are produced by some bacteria and archaea. GTAs morphologically resemble small phage-like particles and contain random fragments of their host genome. They are produced only by a small fraction of the microbial population and are released through a lysis of the host cell. Bioinformatic analyses suggest that GTAs are especially abundant in the taxonomic class of Alphaproteobacteria, where they are vertically inherited and evolve …
Genome-Scale Methylation Analysis In Blood And Tumor Identifies Immune Profile, Age Acceleration, And Dna Methylation Alterations Associated With Bladder Cancer Outcomes, Ji-Qing Chen
Dartmouth College Ph.D Dissertations
Bladder cancer patients receive frequent screening due to the high tumor recurrence rate (more than 60%). Nowadays, the conventional monitoring method relies on cystoscopy which is highly invasive and increases patient morbidity and burden to the health care system with frequent follow-up. As a result, it is urgent to explore novel markers related to the outcomes of bladder cancer. Immune profiles have been associated with cancer outcomes and may have the potential to be biomarkers for outcomes management. However, little work has been conducted to investigate the associations of immune cell profiles with bladder cancer outcomes. Here, I utilized the …
Regulation Of The Wnt/Wingless Receptor Lrp6/Arrow By The Deubiquitylating Complex Usp46, Zachary T. Spencer
Regulation Of The Wnt/Wingless Receptor Lrp6/Arrow By The Deubiquitylating Complex Usp46, Zachary T. Spencer
Dartmouth College Ph.D Dissertations
The evolutionarily conserved Wnt/Wingless signal transduction pathway is critical for the proper development of all animals and implicated in numerous diseases in adulthood. Upon binding of the Wnt/Wingless ligand, a cascade of events culminates in inactivation of the destruction complex, a negative regulator of the pathway, and the subsequent formation of singalosomes which mediate pathway activation. A critical component of signalosome formation is the Wnt/Wingless receptor LRP6/Arrow. Upon canonical pathway activation, LRP6/Arrow undergoes activation via phosphorylation by several kinases and complexes with another Wnt/Wingless receptor Frizzled, along with several cytoplasmic components. While many studies have investigated the regulatory mechanisms of …
Cell-Typing And Interaction Analysis Of The Immune Compartment Of The Tumor Microenvironment Using High-Resolution Omics Modalities, Courtney Taylor Schiebout
Cell-Typing And Interaction Analysis Of The Immune Compartment Of The Tumor Microenvironment Using High-Resolution Omics Modalities, Courtney Taylor Schiebout
Dartmouth College Ph.D Dissertations
Single-cell RNA-sequencing (scRNA-seq) has provided a new frontier for the investigation of complex tissues. One ideal candidate for the utilization of this method is the tumor microenvironment (TME). The TME is often host to a complex set of cell populations and behaviors that can be highly influential for cancer inhibition or progression. This is especially true of the immune compartment of the TME: the presence of certain types of immune cells in the TME and their expression profiles can significantly affect cancer prognosis in some cases. By providing individual cell-level gene expression data, scRNA-seq can be highly informative for characterizing …
Characterization Of Cell Type-Specific Molecular Heterogeneity In Cancer Using Multi-Omic Approaches, Min Kyung Lee
Characterization Of Cell Type-Specific Molecular Heterogeneity In Cancer Using Multi-Omic Approaches, Min Kyung Lee
Dartmouth College Ph.D Dissertations
Tumors are composed of heterogeneous cell types each with its own unique molecular profiles. Recent advances in single cell genomics technologies have begun to increase our understanding of the molecular heterogeneity that exists in tumors with particular focus on gene expression and chromatin accessibility profiles. However, due to limitations in methods for certain sample types and high cost for single cell genomics, bulk tumor molecular profiling has been and remains widely used. In addition, other facets of single cell epigenomic profiling, particularly methylation and hydroxymethylation, remains underexplored. Thus, investigations to understand the cell type specific epigenetic heterogeneity and the cooperation …
The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown
The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown
Dartmouth College Ph.D Dissertations
The Epithelial-to-Mesenchymal transition, a critical cellular process in development, is frequently co-opted by solid tumors to promote invasion and metastasis. In particular, the hybrid or intermediate EMT state, possessing both epithelial and mesenchymal characteristics, is associated with increased cancer stemness and plasticity. Similarly, intra-tumoral heterogeneity in solid tumors, in particular breast cancer, is associated with poor prognosis, tumor growth, proliferation, drug resistance, and metastasis. We sought to understand the link between the generation of intra-tumoral heterogeneity and the intermediate EMT state and their impact on tumor progression and patient prognosis. As part of my thesis work, I developed a model …