Life Sciences Commons^™

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv

Dissertations & Theses (Open Access)

Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …

A Pilot Study Comparing The Efficacy Of Lactate Dehydrogenase Levels Versus Circulating Cell-Free Micrornas In Monitoring Responses To Checkpoint Inhibitor Immunotherapy In Metastatic Melanoma Patients., Matias A Bustos, Rebecca Gross, Negin Rahimzadeh, Hunter Cole, Linh T Tran, Kevin Tran, Ling Takeshima, Stacey L Stern, Steven O'Day, Dave Hoon

Articles, Abstracts, and Reports

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients' disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients' responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 …

A Mechanistic And Genomic Analysis Of Molluscum Contagiosum Virus Immune Evasion, Ian Benjamin Harvey

Arts & Sciences Electronic Theses and Dissertations

Molluscum contagiosum virus (MCV) is a common human-specific poxvirus with a proclivity for

infecting children and the immune-compromised. A characteristic MCV infection is restricted to

the epidermal layers of the skin and can persist for weeks to years in an otherwise healthy

individual. The high clinical burden of MCV is at odds with our limited knowledge regarding how

it successfully evades the human immune response, which is in part due to the lack of an animal

model or cell line to propagate the virus. Through this dissertation, we have uncovered and

characterized a novel mechanism by which MC80, a protein …

Brainstem Ischemic Syndrome In Juvenile Nf2., John W Henson, Tara Benkers, Connor Mccormick

Articles, Abstracts, and Reports

Objective: A new case of brainstem ischemic necrosis in a young woman with de novo neurofibromatosis type 2 (NF2) is reported, and given notable similarities to 7 prior cases of brainstem stroke in the literature, features defining a possible syndrome were sought.

Methods: Case review including detailed clinical assessment, neuroimaging analysis, genetic testing, and brain biopsy, followed by a multicase analysis.

Results: Brainstem ischemia in juvenile NF2 typically occurs in teenagers without previously known NF2 as an acute, monophasic presentation with restricted diffusion in the midbrain or pons following a recent hypoperfusion event, normal vascular imaging, obvious intracranial imaging features …

Machine Learning Approaches For Fracture Risk Assessment: A Comparative Analysis Of Genomic And Phenotypic Data In 5130 Older Men, Qing Wu, Fatma Nasoz, Jongyun Jung, Bibek Bhattarai, Mira V. Han

Public Health Faculty Publications

The study aims were to develop fracture prediction models by using machine learning approaches and genomic data, as well as to identify the best modeling approach for fracture prediction. The genomic data of Osteoporotic Fractures in Men, cohort Study (n = 5130), were analyzed. After a comprehensive genotype imputation, genetic risk score (GRS) was calculated from 1103 associated Single Nucleotide Polymorphisms for each participant. Data were normalized and split into a training set (80%) and a validation set (20%) for analysis. Random forest, gradient boosting, neural network, and logistic regression were used to develop prediction models for major osteoporotic fractures …

Meta-Analysis Of The Alzheimer's Disease Human Brain Transcriptome And Functional Dissection In Mouse Models., Ying-Wooi Wan, Rami Al-Ouran, Carl G Mangleburg, Thanneer M Perumal, Tom V Lee, Katherine Allison, Vivek Swarup, Cory C Funk, Chris Gaiteri, Mariet Allen, Minghui Wang, Sarah M Neuner, Catherine C Kaczorowski, Vivek M Philip, Gareth R Howell, Heidi Martini-Stoica, Hui Zheng, Hongkang Mei, Xiaoyan Zhong, Jungwoo Wren Kim, Valina L Dawson, Ted M Dawson, Ping-Chieh Pao, Li-Huei Tsai, Jean-Vianney Haure-Mirande, Michelle E Ehrlich, Paramita Chakrabarty, Yona Levites, Xue Wang, Eric B Dammer, Gyan Srivastava, Sumit Mukherjee, Solveig K Sieberts, Larsson Omberg, Kristen D Dang, James A Eddy, Phil Snyder, Yooree Chae, Sandeep Amberkar, Wenbin Wei, Winston Hide, Christoph Preuss, Ayla Ergun, Phillip J Ebert, David C Airey, Sara Mostafavi, Lei Yu, Hans-Ulrich Klein, Accelerating Medicines Partnership, Alzheimer’S Disease Consortium, Gregory W Carter, David A Collier, Todd E Golde, Allan I Levey, David A Bennett, Karol Estrada, T Matthew Townsend, Bin Zhang, Eric Schadt, Philip L De Jager, Nathan D Price, Nilüfer Ertekin-Taner, Zhandong Liu, Joshua M Shulman, Lara M Mangravite, Benjamin A Logsdon

Articles, Abstracts, and Reports

We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic …

Inter-Tumor Heterogeneity-Melanomas Respond Differently To Gm-Csf-Mediated Activation., Adi Moshe, Sivan Izraely, Orit Sagi-Assif, Sapir Malka, Shlomit Ben-Menachem, Tsipi Meshel, Metsada Pasmanik-Chor, Dave Hoon, Isaac P Witz

Articles, Abstracts, and Reports

Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. The results of the present study point to inter-tumor heterogeneity as a possible mechanism accounting for the contrasting responses to GM-CSF incorporating therapies. Employing xenograft models of human melanomas in nude mice developed in our lab, we detected differential functional responses of melanomas from different patients to GM-CSF both in vitro as well as in vivo. …

A Strategic Plan To Thread Genomics Competencies Into Undergraduate Curriculum, Holly Mathis

Dissertations

Problem: Genomics in undergraduate nursing education has experienced slow adoption in the United States. Various approaches have been proposed but do not address barriers to successful implementation.

Methods: A strategic plan was developed to increase the amount of genetics and genomic content in the curriculum of an undergraduate nursing program. A gap analysis was performed on the curriculum revealing a paucity of content. A SWOT analysis informed the strategic plan, which included a faculty education program using the ANA/ISONG’s Essentials of Genetic and Genomic Nursing: Competencies, Curricula Guidelines and Outcome Indicators (2^nd ed.) (2009) as a foundation.

Results: Faculty …

Epigenetics A Decolonizing Science, Wade Paul

Electronic Thesis and Dissertation Repository

Epigenetics is the study of gene expression that does not entail alterations to the actual DNA. Decolonization is a theoretical and political movement that seeks to deconstruct colonial institutions and ideologies and reconstruct new and balanced approaches that accept and respect Indigenous worldviews. This project studies the decolonizing potential of epigenetics. Using genealogy as the method, the study establishes a long history of reductionist and deterministic thought that shaped the study of genetic science. Particular instances like thrift gene theory are explored to highlight how genetic explanations have been detrimental to the health and wellbeing of Indigenous people and illustrate …

Advancing Human Health In The Decade Ahead: Pregnancy As A Key Window For Discovery: A Burroughs Wellcome Fund Pregnancy Think Tank., Yoel Sadovsky, Sam Mesiano, Graham J Burton, Michelle Lampl, Jeffrey C Murray, Rachel M Freathy, Anita Mahadevan-Jansen, Ashley Moffett, Nathan D Price, Paul H Wise, Derek E Wildman, Ralph Snyderman, Nigel Paneth, John Anthony Capra, Marcelo A Nobrega, Yaacov Barak, Louis J Muglia

Articles, Abstracts, and Reports

Recent revolutionary advances at the intersection of medicine, omics, data sciences, computing, epidemiology, and related technologies inspire us to ponder their impact on health. Their potential impact is particularly germane to the biology of pregnancy and perinatal medicine, where limited improvement in health outcomes for women and children has remained a global challenge. We assembled a group of experts to establish a Pregnancy Think Tank to discuss a broad spectrum of major gestational disorders and adverse pregnancy outcomes that affect maternal-infant lifelong health and should serve as targets for leveraging the many recent advances. This report reflects avenues for future …

Genomic Diversity Of Bacteriophages Infecting Microbacterium Spp, Deborah Jacobs-Sera, Nathan S. Reyna, Lawrence A. Abad, Richard M. Alvey, Kirk R. Anders, Haley G. Aull, Suparna S. Bhalla, Lawrence S. Blumer, David W. Bollivar, J. Alfred Bonilla, Kristen A. Butela, Roy J. Coomans, Steven G. Cresawn, Tom D'Elia, Arturo Diaz, Ashley M. Divens, Nicholas P. Edgington, Gregory D. Frederick, Maria D. Gainey, Rebecca A. Garlena, Kenneth W. Grant, Susan M.R. Gurney, Heather L. Hendrickson, Lee E. Hughes, Margaret A. Kenna, Karen K. Klyczek, Hari Kotturi, Travis N. Mavrich, Angela L. Mckinney, Evan C. Merkhofer, Jordan Moberg Parker, Sally D. Molloy, Denise L. Monti, Dana A. Pape-Zambito

Articles

The bacteriophage population is vast, dynamic, old, and genetically diverse. The genomics of phages that infect bacterial hosts in the phylum Actinobacteria show them to not only be diverse but also pervasively mosaic, and replete with genes of unknown function. To further explore this broad group of bacteriophages, we describe here the isolation and genomic characterization of 116 phages that infect Microbacterium spp. Most of the phages are lytic, and can be grouped into twelve clusters according to their overall relatedness; seven of the phages are singletons with no close relatives. Genome sizes vary from 17.3 kbp to 97.7 kbp, …

Scalable Profiling And Visualization For Characterizing Microbiomes, Camilo Valdes

FIU Electronic Theses and Dissertations

Metagenomics is the study of the combined genetic material found in microbiome samples, and it serves as an instrument for studying microbial communities, their biodiversities, and the relationships to their host environments. Creating, interpreting, and understanding microbial community profiles produced from microbiome samples is a challenging task as it requires large computational resources along with innovative techniques to process and analyze datasets that can contain terabytes of information.

The community profiles are critical because they provide information about what microorganisms are present in the sample, and in what proportions. This is particularly important as many human diseases and environmental disasters …