Medicine and Health Sciences Commons^™

The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle

International Undergraduate Journal of Health Sciences

Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …

Loss Of Pml Nuclear Bodies In Familial Amyotrophic Lateral Sclerosis-Frontotemporal Dementia, Francesco Antoniani, Marco Cimino, Laura Mediani, Jonathan Vinet, Enza M. Verde, Valentina Secco, Alfred Yamoah, Priyanka Tripathi, Eleonora Aronica, Maria Elena Cicardi, Davide Trotti, Jared Sterneckert, Anand Goswami, Serena Carra

Farber Institute for Neuroscience Faculty Papers

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share genetic causes and pathogenic mechanisms. The critical genetic players of ALS and FTD are the TARDBP, FUS and C9orf72 genes, whose protein products, TDP-43, FUS and the C9orf72-dipeptide repeat proteins, accumulate in form of cytoplasmic inclusions. The majority of the studies focus on the understanding of how cells control TDP-43 and FUS aggregation in the cytoplasm, overlooking how dysfunctions occurring at the nuclear level may influence the maintenance of protein solubility outside of the nucleus. However, protein quality control (PQC) systems that maintain protein homeostasis comprise …

Migratory Material: Epigenetics & Weaving At The Us-Mexico Border, Valerie Navarrete

Masters Theses

Discourse often sutures the body shut, disallowing representations of identity to outgrow sociopolitical interests. This issue may originate from borders, but also from the unnamable pathology that generational colonial trauma transmits to the mind, body, and environment. Without a direct form of translatability, this thesis proposes a new materialism that deviates from any object-oriented ontology. Untethered and intra-active, epigenetics and weaving represent objects that transform typical ways of knowing and seeing. Their sensitivity to the environment, in addition to their mobility across generations of time, broaden the spatiotemporal loci of the body and its embodiment. Proposing new materials that expand …

The Opioid Epidemic: How Genetics Play A Role In Addiction And Treatment, Kirsten Houston

Honors College Theses

The opioid epidemic is an issue within the pharmaceutical industry in the United States of America due to prescription and non-prescription substances being made available to the population. Opioids include chemical substances that affect the body and brain through opioid receptors, including the mu, kappa, and delta receptors. These substances are derived and synthesized from the poppy plant. Multiple causes have been linked to opioid abuse disorder, including but not limited to employment, income, housing, nutrition, mental health disorders, and genetics. By gathering information from previous literature, genetics may be the main cause of narcotic analgesic tolerance and abuse. Specific …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations & Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Understanding The Expression And Role Of Pros-1 In The Male Gonad Of C. Elegans, Jack Bozik

Undergraduate Theses

The gene pros-1 is a transcription factor that is highly expressed within neuronal sheath cells, glial cells, and excretory canal cells. pros-1 plays a role in cell determination of those cell types in the nematode C. elegans, which promotes organismal development. But the degree to which pros-1 presence is important is still not fully understood, because there are many genes involved in development that when mutated or damaged can result in unexpected phenotypes or even total loss of function to a certain developmental mechanism. What makes pros-1 valuable to research is that it is a functional homologue to a …

Protocol To Identify The Core Gene Supported By An Essential Gene In E. Coli Bacteria Using A Genome-Wide Suppressor Screen, Isao Masuda, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

We describe here a genome-wide screening approach to identify the most critical core reaction among a network of many that are supported by an essential gene to establish cell viability. We describe steps for maintenance plasmid construction, knockout cell construction, and phenotype validation. We then detail isolation of suppressors, whole-genome sequencing analysis, and reconstruction of CRISPR mutants. We focus on E. coli trmD, which encodes an essential methyl transferase that synthesizes m1G37 on the 3'-side of the tRNA anticodon. For complete details on the use and execution of this protocol, please refer to Masuda et al. (2022).

Paternal Ages And Genetic Diseases And Congenital Anomalies, Neda Hamood

The Pegasus Review: UCF Undergraduate Research Journal

he purpose of this research is to investigate the link between Advanced Paternal Ages (APA) (i.e., APA ≥ 35 years and APA ≥ 50 years) and genetic diseases and congenital anomalies. Currently, the relationship between both APA and genetic diseases and congenital anomalies remains unclear. There is room for improvement, however, to investigate systematically the relationship between specific congenital anomalies in newborns and APA. More recently, the link between APA (as opposed to existing studies analyzing Advanced Maternal Age alone) and genetic diseases has been recognized by researchers, epidemiologists, and various health experts. Thus, this study serves to examine the …

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G. Izquierdo, Jing Chen, Richard Packer, Robert J. Hall, Anna L. Guyatt, Chiara Batini, Rebecca J. Thompson, Chandan Puvuluri, Vidhi Malik, Brian D. Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A. Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Sinjini Sikdar, Martin D. Tobin, Et Al.

Mathematics & Statistics Faculty Publications

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of …

Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac

Theses and Dissertations--Physiology

Elucidating the relationship of the gut microbiome in Alzheimer's Disease (AD) risk and pathogenesis is an area of intense interest. Since 60 to 80% of AD risk is related to genetics and APOE alleles represent the most impactful genetic risk factors for AD, their mechanism(s) of action are under intense scrutiny.

First, I conducted a study on APOE targeted replacement mice to investigate the impact of APOE alleles on the murine gut microbiome. The relative abundance of bacteria from the family Ruminococacceae and related genera increased with APOE2 status. The relative abundance of the class Erysipelotrichia increased with APOE4 status, …