Combining Network Modeling And Experimental Approaches To Predict Drug Combination Responses, Deepraj Sarmah

All Dissertations

Cancer is a lethal disease and complex at multiple levels of cell biology. Despite many advances in treatments, many patients do not respond to therapy. This is owing to the complexity of cancer-genetic variability due to mutations, the multi-variate biochemical networks within which drug targets reside and existence and plasticity of multiple cell states. It is generally understood that a combination of drugs is a way to address the multi-faceted drivers of cancer and drug resistance. However, the sheer number of testable combinations and challenges in matching patients to appropriate combination treatments are major issues.

Here, we first present a …

Data-Driven Biomarker Panel Discovery In Ovarian Cancer Using Heterogenous Data Fusion On Exosomal And Non-Exosomal Microrna Expression Data, Paritra Mandal

All Dissertations

Ovarian cancer (OC) is an aggressive gynecological cancer and is currently the 5th leading cause of deaths due to cancer in women. High mortality rates are attributable to the vague pathogenesis and asymptomatic nature of the early stages. The development of a liquid biopsy for routine OC screening could help identify the disease at an earlier stage, making treatments more likely to be effective thereby increasing survival rates. Exosomes, small (~100nm) extracellular vesicles present in body fluids, have been shown to contain cancer-progression, onset, and related factors, making them good candidates for use in liquid biopsies. However, to date, only …

Taxonomic Revision And Morphometric Analysis Of Selected Anthurium (Araceae) Species From Bolivia And Peru, Daniel M. Tarazona Ocana

Theses

The genus Anthurium (Araceae) consists of around 1,200 species distributed in the Neotropics, particularly in Central and South America. The montane forests in the eastern flank of the Andes, ranging from northern Ecuador to central Bolivia; hereafter, the East Andes Gradient region, are particularly rich in terms of species diversity, and include an understudied group of Anthurium species endemic to the region. Within this group of species, some taxa are difficult to distinguish from each other mainly due to the lack of identification keys, incomplete species descriptions and unknown synonyms. In this study, a combination of traditional taxonomic techniques and …

Modularity And Boolean Network Decomposition, Matthew Wheeler

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Nonlinearity Of Regulation In Biological Networks, Santosh Manicka, Kathleen Johnson, Michael Levin, David Murrugarra

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Modularity In Gene Regulatory Networks, Mehak Kapoor, Claus Kadelka

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Systems Pharmacology Dissection Of The Mechanisms And Therapeutic Potential Of Cassiae Semen For Hepatoprotection And Brightening Eyes, Jing-Xiao Zhang, Zi-Yi Chen, Xue-Zhen Huang, Lin-Yue Qi, Wei Zhou

Journal of Food and Drug Analysis

Cassiae semen has been shown to play significant roles in reversing “liver fire” to improve vision. The systems mechanism of Cassiae semen for hepatoprotection and brightening eyes has not been fully explored. The systems pharmacology approach is proposed to dissect the potential pharmacological mechanism of Cassiae semen for hepatoprotection and brightening eyes. The results showed that 26 active components of Cassiae semen that connected with 230 targets were obtained. Gene ontology enrichment, network and pathway analysis explored that Cassiae semen is responsible for hepatoprotection and brightening eyes. The current study will contribute to the research and development of functional foods.

Prenatal Choline Supplementation During Maternal Obesity Alters Offspring Response To Western Diets, Hunter W. Korsmo

Dissertations, Theses, and Capstone Projects

Maternal obesity has led to an increase in adverse offspring developmental outcomes and a greater risk for long-term metabolic diseases. Choline, a semi-essential nutrient, can be incorporated into phosphatidylcholine (PC) as well as sphingomyelin (SM) and donate its labile methyl group for the remethylation of homocysteine after choline is oxidized to betaine. Prenatal choline insufficiency has been related to maternal obesity and metabolic diseases, such as metabolic associated fatty liver disease (MAFLD). Choline may interact with maternal obesity to influence the programming offspring.

Chapter 1 presents an introduction of choline and the various clinical outcomes associated with choline supplementation during …

Drone-Based Water Sampling And Characterization Of Three Freshwater Harmful Algal Blooms In The United States, Regina Hanlon, Stephen J. Jacquemin, Johnna A. Birbeck, Judy A. Westrick, Charbel Harb, Hope Gruszewski, Andrew P. Ault, Durelle Scott, Hosein Foroutan, Shane D. Ross, Javier González-Rocha, Craig Powers, Lowell Pratt, Harry Looney, Greg Baker, David G. Schmale

Biological Sciences Faculty Publications

Freshwater harmful algal blooms (HABs), caused mostly by toxic cyanobacteria, produce a range of cyanotoxins that threaten the health of humans and domestic animals. Climate conditions and anthropogenic influences such as agricultural run-off can alter the onset and intensity of HABs. Little is known about the distribution and spread of freshwater HABs. Current sampling protocols in some lakes involve teams of researchers that collect samples by hand from a boat and/or from the shoreline. Water samples can be collected from the surface, from discrete-depth collections, and/or from depth-integrated intervals. These collections are often restricted to certain months of the year, …

Methods And Tools To Improve Performance Of Plant Genome Analysis, Drew Ferrell

Theses and Dissertations

Multi -omics data analysis and integration facilitates hypothesis building toward an understanding of genes and pathway responses driven by environments. Methods designed to estimate and analyze gene expression, with regard to treatments or conditions, can be leveraged to understand gene-level responses in the cell. However, genes often interact and signal within larger structures such as pathways and networks. Complex studies guided toward describing dynamic genetic pathways and networks require algorithms or methods designed for inference based on gene interactions and related topologies. Classes of algorithms and methods may be integrated into generalized workflows for comparative genomics studies, as multi -omics …

Tau-Dependent Neurodegeneration And Alleviation By Etas®50, Clifford Tyree Castleberry

Theses (2016-Present)

Brain growth factors are a broad group of molecules that enable the brain to adapt to stress. In a study on Alzheimer’s mice (APP), we tested the role of an asparagus supplement, ETAS®50, to mitigate the stress caused by the Alzheimer’s condition in this mouse model. Gene expression data revealed regulation of genes related to neuronal growth and function, such as tau, which were severely stressed in the APP mice to be alleviated.

The Effects Of Host-Like Environmental Signals And Gene Expression On Capsule Growth In Cryptococcus Neoformans, Yu Min Jung

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cryptococcus neoformans is a fungal pathogen that causes cryptococcosis, a disease that kills almost 200,000 people worldwide each year. A unique feature of this deadly yeast is its polysaccharide capsule, which is known to be associated with its virulence. Here, we systematically explore the effects of all possible combinations of 4 capsule-inducing signals on gene expression, cell size, and capsule size. These signals are medium (YPD, DMEM or RPMI), temperature (30°C or 37°C), CO₂ (room air or 5%), cAMP (0 mM or 20 mM), and pH buffer (HEPES/no HEPES). We explore the effects of exogenous cAMP at a range …

The Mayfly Newsletter, Donna Giberson

The Mayfly Newsletter

The Mayfly Newsletter is the official newsletter of the Permanent Committee of the International Conferences on Ephemeroptera.

Parasitism Of Corn Earworm, Helicoverpa Zea (Boddie) (Lepidoptera: Noctuidae), By Tachinid Flies In Cultivated Hemp, Armando Falcon-Brindis, John O. Stireman Iii, Zenaida J. Viloria, Raul T. Villanueva

Biological Sciences Faculty Publications

In a survey on hemp grown in western Kentucky we found an average of 27.8 CEW larvae per plant. We recorded 45% parasitism of CEW in these fields by two species of tachinid flies, Winthemia rufopicta and Lespesia aletiae. Most parasitized larvae were third to sixth instars at the time of collection. We found up to 22 tachinid eggs per host larva, 89% of which typically bore between 1 and 5 eggs on the thorax. 45.9% of CEW bearing eggs died. The number of tachinid eggs per host was unrelated to host body mass, but both the number of tachinid …

Symmetry-Inspired Analysis Of Biological Networks, Ian Leifer

Dissertations, Theses, and Capstone Projects

The description of a complex system like gene regulation of a cell or a brain of an animal in terms of the dynamics of each individual element is an insurmountable task due to the complexity of interactions and the scores of associated parameters. Recent decades brought about the description of these systems that employs network models. In such models the entire system is represented by a graph encapsulating a set of independently functioning objects and their interactions. This creates a level of abstraction that makes the analysis of such large scale system possible. Common practice is to draw conclusions about …

Inferring Dynamics Of Biological Systems, Tracey G. Oellerich

Biology and Medicine Through Mathematics Conference

No abstract provided.

Combining Pharmacokinetics And Vibrational Spectroscopy: Mcr-Als Hard-And-Soft Modelling Of Drug Uptake In Vitro Using Tailored Kinetic Constraints, David Perez-Guaita, Guillermo Quintas, Zeineb Farhane, Roma Tauler, Hugh Byrne

Articles

Raman microspectroscopy is a label-free technique which is very suited for the investigation of pharmacokinetics of cellular uptake, mechanisms of interaction, and efficacies of drugs in vitro. However, the complexity of the spectra makes the identification of spectral patterns associated with the drug and subsequent cellular responses difficult. Indeed, multivariate methods that relate spectral features to the inoculation time do not normally take into account the kinetics involved, and important theoretical information which could assist in the elucidation of the relevant spectral signatures is excluded. Here, we propose the integration of kinetic equations in the modelling of drug uptake and …

Exploiting Chemogenetic And Genetic Interactions In Human Cells As An Avenue For New Therapeutic Opportunities, Medina Colic

Dissertations and Theses (Open Access)

The advent of CRISPR technology and its adaptation to the mammalian genome made whole-genome knockout screens possible directly in human cells. Gene knockout answers how essential that gene is for cell fitness and proliferation. Genes showing moderate to severe fitness defects are called essential genes and provide insights into disease-specific candidate therapeutic targets. Additionally, CRISPR offers other applications for genome editing. Two applications this dissertation is based on are 1) combination of gene knockout and drug treatment, which enables the identification of chemogenetic interactions, or gene mutations that enhance or suppress the activity of a drug, and 2) combinatorial editing, …

Elucidating The Cellular Physiology Of Glyphosate Resistance In Palmer Amaranth (Amaranthus Palmeri) Using Integrated Omics Approaches, Pawanjit Kaur Sandhu

All Theses

The evolution of resistance to herbicides in weeds poses a major threat to agricultural production systems. To date, herbicide resistance has been reported against 21 modes of action in 266 weed species across 71 countries. More than 50 weed species have developed resistance against glyphosate, the most widely used herbicide worldwide. Although several mechanisms of glyphosate resistance have been discovered, our understanding of alterations in the cellular physiology of glyphosate-resistant weed biotypes, and the induction of the resistance mechanisms remains limited. This knowledge is critical to developing sustainable weed management practices and for a comprehensive understanding of plant stress adaptations. …

Periodic Spatial Disturbances Alter The Expression Of Quorum Sensing Virulence Factors In Pseudomonas Aeruginosa, Laura García-Diéguez

All HCAS Student Capstones, Theses, and Dissertations

Pseudomonas aeruginosa is an opportunistic pathogen associated with severe acute and chronic illnesses. Current antibiotic-based approaches fail to effectively treat P. aeruginosa infections due to the effectiveness and robustness of the quorum sensing signaling system (QS). Pathogenic bacteria, such as P. aeruginosa, employ this population density-dependent communication mechanism to confer antimicrobial resistance, propagate infection, and coordinate the expression of virulence factors, through the production and detection of autoinducing signaling molecules (AI). As such, there is a growing interest in developing novel non-antibiotic-based techniques to attenuate the pathogenicity of P. aeruginosa by disrupting the functionality of its QS system. Previous …