Life Sciences Commons^™

Exploring The Potential Pathogenicity Of A Type 2 Diabetes Mellitus Associated Insr Missense Variant Of Uncertain Significance Through Daf-2 In The Caenorhabditis Elegans Model, Brittany White

Theses

Type 2 diabetes mellitus (T2DM) is hallmarked by insulin resistance, with the INSR gene identified as a key player in this condition in humans. This gene is known to harbor genetic variants with a wide range of clinical significance from pathogenic to variants of uncertain significance (VUS) to benign. This project investigates a VUS associated with T2DM identified through ClinVar. A gene mutational analysis, predictive amino acid substitution analysis, and protein modeling predict INSR c.1628C>T (p. Thr543Met) to be likely pathogenic or damaging. PolyPhen-2 predicts this variant to be probably damaging (HumDiv score of 1.000).

Evolutionary conservation of the …

Documenting The Southern Range Terminus Of The Wood Frog (Lithobates Sylvaticus) In North America, Christian Braswell

Theses

The Wood Frog (Lithobates sylvaticus) holds a remarkable position in North American amphibian biology, with its range extending from the Arctic Circle down to the near sub-tropical southeastern United States. This thesis presents a novel quantitative polymerase chain reaction analysis (qPCR) primer specific to L. sylvaticus and a survey effort regarding the southernmost distribution and detection of this species in Alabama through the application of environmental DNA (eDNA) sampling techniques. By investigating historical data and employing advanced genetic methodologies, this research provides insights into the contemporary status and distribution of the Wood Frog. This research is important to …

Characterization Of Antimicrobial Properties Of Excrement And Functional Microbiome Of Black Vultures (Coragyps Atratus), Bridgette Gray

Theses

Black vultures, Coragyps atratus, are obligate scavenging birds that consume and dispose of decaying carcasses and carrion. They fulfill a key ecological niche in the environments in which they live. It has been observed that these vultures sometimes excrete bodily waste onto their legs. This adaptive behavior could help aid them in controlling bacteria and other microbes they encounter while stepping into a carcass to eat. This study directly examined the antimicrobial properties of the excrement of black vultures across various bacterial species utilizing a zone of inhibition test and a nematode species utilizing a survival assay. The black vulture …

An Evolutionary Comparative Study Of Congenital Stationary Night Blindness-Associated Trpm1 Genetic Variants Of Uncertain Significance In Horses And Humans Utilizing Caenorhabditis Elegans, Gabrielle Davis

Theses

Congenital stationary night blindness (CSNB) is a heterogeneous collection of genetic diseases affecting the eyes and vision in horses and humans. Current research has implicated several genetic mutations impacting different genes involved in phototransduction and signal transmission, including TRPM1. In horses, genetic mutations in TRPM1 also result in a leopard spotting pattern or leopard complex. The goal of this study is to examine the potential impact of CSNB associated TRPM1 missense variants of uncertain significance (VUS). Previous research in Caenorhabditis elegans have revealed an orthologous TRPM1 gene known as gon-2 that allows for comparative studies. The evolutionary relationship of …

Molecular Evidence Of Cryptic Hybridization In The Japanese Nezasa Bamboos (Pleioblastus Section Nezasa), Ryan Long

Theses

The genus Pleioblastus is a complex group of Southeast Asian temperate bamboos with 7-21 species, depending on taxonomic authority. This study tests the hypothesis that taxonomic complexity in this group is due in part to hybridization and subsequent backcrossing in natural populations, resulting in a reticulate evolutionary history and a contemporary species assemblage that includes cryptic hybrids. This hypothesis is supported by recent research on the temperate bamboos that revealed intergeneric hybrids involving Pleioblastus and other genera of temperate bamboos (Triplett and Clark, 2021). The objective of the current study was to use data from Amplified Fragment Length Polymorphism (AFLP) …

Comparative Modeling And Evolutionary Comparison Of Serine Protease, A Timber Rattlesnake Venom Protein, Qawer Ayaz

Theses

The aim of this study is to create a homology model of VG35 serine protease and evaluate the evolutionary comparison of secondary structure on basis of protein model using YASARA. This method was furthermore used to predict the potential epitopes which can help in the investigation of future studies.

The VG35 was used to run a BLAST search which gave most resembled serine protease of different species which was then translated and modeled in YASARA. The modeled protein data was then used to determine the secondary structure. This was then used for evolutionary comparison of all proteins to VG35. Then …

Cryptic Hybridization In The Temperate Bamboos: Is Pleioblastus Simonii A Species Of Hybrid Origin?, Morgan Brown

Theses

Japanese river bamboo (Pleioblastus simonii, ‘medake,’‘kawadake’) is an ecologically important species of temperate bamboo native to Japan. This species is widely known and historically important in Japanese rural farm life. Based on morphological data, Japanese river bamboo is classified in Pleioblastus section Medakea (Poaceae: Bambusoideae) along with five other Japanese species, which are collectively considered to represent a phylogenetically distinct lineage. However, recent studies suggest that Japanese river bamboo may have arisen as a result of previously undetected hybridization (i.e., cryptic hybridization), while also calling into question the diversity of section Medakea. The role of hybridization in natural plant populations …

Crystallographic Structure Determination Of Bacteriophage-Encoded Enzymes That Specifically Target Pathogenic Bacteria, Marta Sanz Gaitero

Theses

Antibiotic resistance is becoming a serious public health concern. Infections that some decades ago could be treated with antibiotics now sometimes do not respond to traditional treatment, causing higher mortality and economic losses. An alternative to the use of antibiotics are bacteria's natural predators, bacteriophages (or phages), and specifically their lytic enzymes. These proteins are produced by phages to degrade bacterial peptidoglycan to inject their genetic material into the bacteria (virion-associated peptidoglycan hydrolases) or to release their progeny once the infection is finished (endolysins). They can be applied exogenously to lyse Gram-positive bacteria or be genetically engineered to lyse Gram-negative …

Transcriptomics Of Learning, Pablo Iturralde

Theses

Learning is a basic and important component of behavior yet we have very little empirical information about the interaction between mechanisms of learning and evolution. In our work, we are testing hypotheses about the neurogenetic mechanisms through which animal learning abilities evolve. We are able to test this directly by using experimentally evolved populations of flies, which differ in learning ability. These populations were previously evolved within the lab by creating worlds with different patterns of change following theoretically predicted effects on which enhanced learning will evolve. How has evolution acted to modulate genes and gene expression in the brain …

Efficient Reduced Bias Genetic Algorithm For Generic Community Detection Objectives, Aditya Karnam Gururaj Rao

Theses

The problem of community structure identification has been an extensively investigated area for biology, physics, social sciences, and computer science in recent years for studying the properties of networks representing complex relationships. Most traditional methods, such as K-means and hierarchical clustering, are based on the assumption that communities have spherical configurations. Lately, Genetic Algorithms (GA) are being utilized for efficient community detection without imposing sphericity. GAs are machine learning methods which mimic natural selection and scale with the complexity of the network. However, traditional GA approaches employ a representation method that dramatically increases the solution space to be searched by …

Low Cost, Multi-Purpose Genotyping Panels For Dairy And Beef Cattle, Michelle Judge

Theses

rhe selection of animals based on DNA has revolutionised animal breeding, but the associated high cost of obtaining genotypes has limited its uptake. The objective of this thesis was to develop a low-cost, low-density, multi-purpose genotyping panel for the procurement of reliable genotype information, and to quantify the long-term consequences of using such low-density genotype panels in breeding programs. The objectives were achieved through a combination of real-life cattle genotype data and simulations to mimic a cattle population. The in-silico development of genotype panels was based on actual genotypes from up to 58,705 beef cattle. Alternative novel strategies were used …

In Silico Prediction Of Protein-Protein Interactions Between Cronobacter Sakazakii And Human Host, Sean Held

Theses

The genus Cronobacter accommodates 16 biogroups of the emerging opportunistic pathogen known formerly as Enterobacter sakazakii. Cronobacter are occasional contaminants of milk powder and, consequently, powdered infant formula (PIT). Since it is a pathogen that is transmitted in infant formula it represents a significant health risk to neonates. These bacteria are opportunistic pathogens (can only cause disease when the host's resistance is low) and are linked with life-threatening infections in neonates. Some of the clinical symptoms of Cronohacter infection include necrotizing enterocolitis, bacteremia, and meningitis, with case fatality rates of 50-80% being reported (Healy et al. 2010). Infant formula manufacturers …

Design Of A Distributed Hadoop Solution For The Multiple Sequence Alignment Algorithm: Clustal Omega, Jurate Daugelaite

Theses

Multiple Sequence Alignment (MSA) of DNA and protein sequences is one of the most essential techniques in the fields of molecular biology, computational biology and bioinformatics. It aids the identification and prediction of three dimensional structures, primary functions and evolutionary relatedness amongst groups of species, organisms, and genes. Since as the completion of the Human Genome Project and with the advent of sequencing initiatives such as the Genome 10K project, the rate of genome sequencing has increased exponentially, producing vast amounts of DNA and protein sequences. MSA algorithms, when applied to such sequence data, can identify common homology, structure and …

Dynamic Herbal Monographs For A Digital World, Niamh O'Brien

Theses

Post analysis of a worldwide survey of Medical Herbalists, 93% of respondents were in favour of an online system which could update monographs dynamically. 63% of respondents suggested that some current monographs are out of date and lack certain practicalities in areas such as : Interactions, Dosage and Safety. Research into gaining optimal responses from surveys led to a 78% response rate. Survey analysis resulted in a modem up-to-date monograph template being created and each of the aforementioned information systems tested against same. Testing involved the generation of XML, HTML, PHP and OWL languages for encoding documents to allow for …

Development Of Pcr Assays To Detect And Characterise Salmonella Isolates From Cheese And Meat Products By Utilizing An Integrated Genomics Approach, Noelle Geraldine Mccarthy

Theses

Salmonella is an extremely important foodborne pathogen which is responsible for millions of cases of gastroenteritis annually. Salmonella outbreaks have been associated with numerous common food stuffs such as meat, dairy and seafood. Traditional culture based methods for the detection Salmonella are labourious and costly. Rapid detection and serovar identification would dramatically decrease the time required to identify Salmonella outbreaks and potential health risks.

In the US 99% of all Salmonella infections are caused by members of Salmonella enterica subspecies 1. Serovars within subspecies 1 can vary due to host specificity and pathogenicity. DNA sequencing projects have provided valuable genomic …

Development Of An Automated Thiopurine Methyltransferase (Tpmt) Genotyping Assay, Mary Corcoran

Theses

Thiopurine methyltransferase (TPMT) is a cytosolic enzyme that catalyses the S- methylation of aromatic and sulphydryl compounds known as the thiopurines. These therapeutic agents are used in the treatment of acute lymphoblastic leukemia, autoimmune disorders, inflammatory bowel disease and organ transplant recipients.

Erythrocyte TPMT activity is polymorphic and patients with intermediate or deficient TPMT are at significant risk for excessive toxicity after receiving ‘standard’ doses of thiopurine medications. The activity of TPMT is inherited as an autosomal co-dominant trait. Several mutations in the TPMT gene have been described that correlate with a low activity phenotype. Three mutations G238C, G460A and …

An Assessment Of Prothrombotic Tendency In Humans Using Functional And Genomic Determinants In The South Eastern Irish Population, Carmel Cullen

Theses

Venous thrombosis occurs in about 1 per 1,000 individuals per year. It is a serious disorder and accounts for a significant number of hospital admissions and deaths annually. Thrombophilia describes the familial or acquired disorders of the haemostatic mechanism that predispose to thrombosis. Inherited thrombophilia can be defined as a genetically determined tendency to venous thromboembolism Mutations in genes that code for proteins involved directly (or indirectly) In blood coagulation have been associated with prothrombotic status. Laboratory investigations for thrombophilia include screening for deficiencies of antithrombin, protein C or protein S and testing for activated protein C resistance. Together these …

Whole Genome Sequencing Of L.Monocytogenes And L.Innocua : A Basis For Comparative Genomics Of The Genus Listeria, Rachel Purcell

Theses

Listeria monocytogenes is a gram-positive, food-borne human and animal pathogen. L.innocua is a non-pathogenic species the most closely related to L. monocytogenes. Comparative genomics between a pathogenic and a closely related non-pathogenic species is a powerful approach for identifying genes or regions on the chromosome, which might be involved in virulence. Therefore whole genome sequencing of these two organisms was undertaken. The strategy used was based on a random approach combined with end-sequencing of a medium insert library for the finishing phase. Based on the available sequence data for these two species an in silico analysis for the presence of …

Methicillin Resistant Staphylococcus Aureus (Mrsa): Molecular Detection And Dna Fingerprinting, Leslie Cotter

Theses

Throughout the 1990s, the incidence of methicillin-resistant Staphylococcus aureus has increased in many health care areas including acute and chronic care facilities, outpatient clinics and in the community. Once introduced into a health care environment, this nosocomial pathogen can spread rapidly and as MRSA are resistant to multiple antibiotics, treatment is often difficult. Therefore effective infection control measures are required to prevent cross-infection and further spread of endemic strains.

In this study, a sensitive and specific triplex-PCR assay was designed for MRSA detection, wherein three genes, the methicillin resistance gene (mecA). femA and the extracellular thermonuclease gene (rmc) were simultaneously …

Molecular Analysis Of The Factor V-Leiden Mutation In A Cardiac Transplant Patient Population, Caroline Maher

Theses

Venous thrombosis is a serious health problem affecting 1 in 1000 individuals annually. Until recently the pathogenic factors underlying thrombosis were associated with genetic defects in protein C, protein S and antithrombin III. However these were recognised in fewer than 5-10% of thrombotic patients. A breakthrough was made with the discovery of activated protein C resistance (APCr) which is associated in 90% of cases v/herein a G-->A transition in the factor V gene results in an abnormal molecule, Factor V Leiden. APCr is a major risk factor for thrombosis being present in 20-60% of thrombotic patients. Recently a G-^A …