Life Sciences Commons^™

Adaptation Reshapes The Distribution Of Fitness Effects, Diego Tenoch Morales Lopez

Electronic Thesis and Dissertation Repository

The process of adaptation has been of interest since the XIX century, when Darwin first proposed the idea of natural selection. Since then, there has been a myriad of theoretical and empirical works that have expanded the field. From the many evolutionary insights these works have produced, a foundational idea is that spontaneous mutations in the genome of organisms can produce changes to their reproductive success that might confer an advantage for the mutant organisms with respect to their peers. Therefore, mutations drive adaptive evolution by virtue of their heritable effects on fitness. Empirical measures of the distribution of these …

On The Origins Of Life — Modelling The Initial Stages Of Complex Coacervate Droplet Formation, Yixuan Wu

Western Libraries Undergraduate Research Awards (WLURAs)

Coacervate droplets are considered a plausible model for protocells due to their spontaneous formation and ability to compartmentalize macromolecules such as nucleic acid and peptides. Although experimental studies have observed and synthesized coacervates under different laboratory conditions, little is known about their structure. Here we present atomistic molecular dynamic simulations of the interactions between water and oppositely charged proteins that cluster together in a salt-dependent process. Observing such liquid-liquid phase separation on an atomic level would serve as a model for the initial stages of complex coacervate formation. Molecular Dynamics was used to compute diagnostics of the structure at different …

Short-Term Versus Long-Term Effects Of Nitrogen Addition And Warming On Ecosystem N Dynamics In A Grass-Dominated Temperate Old Field, Benjamin F. A. Souriol

Electronic Thesis and Dissertation Repository

Increased atmospheric nitrogen (N) deposition and climate warming are both anticipated to influence the ecosystem N dynamics of northern temperate ecosystems substantially over the next century. Nevertheless, in field experiments with N addition and warming treatments, temporal scale can play an important role in determining the extent of treatment effects on N dynamics, and it is unclear to what extent the results of short-term studies can be extrapolated to responses over longer time scales. I compared the short-term versus long-term effects of N addition and warming on net N mineralization, N leaching, and N retention in a grass-dominated old field. …

Protein Stability In Solution And In The Gas Phase., Yousef Haidar

Electronic Thesis and Dissertation Repository

Electrospray Ionization mass spectrometry (ESI-MS) is widely used for probing proteins, yet many aspects of this technique remain elusive. Using MS, ion mobility spectrometry (IMS), and circular dichroism (CD) spectroscopy, this thesis sheds light on the stability differences of proteins in the gas phase and solution. After a general introduction (Chapter 1), Chapter 2 scrutinizes some aspects of native ESI. Our data highlight the significance of cone voltage in maintaining a native-like fold and show the advantage of using NH₄Ac in protein experiments. Chapter 3 focuses on hydrogen/deuterium exchange (HDX)-MS. Several studies have reported that D₂O …

Towards Clinical Microscopic Fractional Anisotropy Imaging, Nico Jj Arezza

Electronic Thesis and Dissertation Repository

Microscopic fractional anisotropy (µFA) is a diffusion-weighted magnetic resonance imaging (dMRI) metric that is sensitive to neuron microstructural features without being confounded by the orientation dispersion of axons and dendrites. µFA may potentially act as a surrogate biomarker for neurodegeneration, demyelination, and other pathological changes to neuron microstructure with greater specificity than other dMRI techniques that are sensitive to orientation dispersion, such as diffusion tensor imaging. As with many advanced imaging techniques, µFA is primarily used in research studies and has not seen use in clinical settings.

The primary goal of this Thesis was to assess the clinical viability of …

Decoy-Target Database Strategy And False Discovery Rate Analysis For Glycan Identification, Xiaoou Li

Electronic Thesis and Dissertation Repository

In recent years, the technology of glycopeptide sequencing through MS/MS mass spectrometry data has achieved remarkable progress. Various software tools have been developed and widely used for protein identification. Estimation of false discovery rate (FDR) has become an essential method for evaluating the performance of glycopeptide scoring algorithms. The target-decoy strategy, which involves constructing decoy databases, is currently the most popular utilized method for FDR calculation. In this study, we applied various decoy construction algorithms to generate decoy glycan databases and proposed a novel approach to calculate the FDR by using the EM algorithm and mixture model.

Addressing The Impact Of Time-Dependent Social Groupings On Animal Survival And Recapture Rates In Mark-Recapture Studies, Alexandru M. Draghici

Electronic Thesis and Dissertation Repository

Mark-recapture (MR) models typically assume that individuals under study have independent survival and recapture outcomes. One such model of interest is known as the Cormack-Jolly-Seber (CJS) model. In this dissertation, we conduct three major research projects focused on studying the impact of violating the independence assumption in MR models along with presenting extensions which relax the independence assumption. In the first project, we conduct a simulation study to address the impact of failing to account for pair-bonded animals having correlated recapture and survival fates on the CJS model. We examined the impact of correlation on the likelihood ratio test (LRT), …

A Highly Charged Topic: Intrinsically Disordered Proteins And Protein Pka Values, Carter J. Wilson

Electronic Thesis and Dissertation Repository

Intrinsically disordered proteins (IDPs) are known not only for their roles in disease but also for their conformational flexibility, which makes them elusive for experimentation. We consider the role played by theory and simulation in resolving important questions pertaining to IDP structure and dynamics, as well as the nature of the charged residues (e.g., glutamate, lysine, etc.) that enrich them. Specifically, we investigated how the deep learning trained AlphaFold2 (AF2) predictor estimates disorder content, revealing both strong performance in relation to conventional approaches and an important relationship between the AF2 confidence metric and IDP dynamics. We also assessed how modern …

The Synthesis And Characterization Studies Of Modified Nucleobase In Pna And Dna, Gyeongsu Park

Electronic Thesis and Dissertation Repository

Nucleic acids have been extensively studied not only for their importance in biological systems as the medium of genetic information but also for their potential uses in therapeutic, diagnostic and other biological applications. As such, modified oligonucleotides and oligonucleotide analogues have drawn the attention of researchers from various disciplines. Modification of oligonucleotides can enhance their desired characteristics and engender unique properties, such as fluorescence, giving rise to a variety of applications. Peptide nucleic acid (PNA) is an oligonucleotide mimic with a pseudo-peptide backbone based on N-(2-aminoethyl)glycine that is renowned for high target binding affinity and resistance to enzyme degradation. …

Pillars Of Biology: 'The Genetical Evolution Of Social Behaviour, I And Ii'., Geoff Wild

Applied Mathematics Publications

None.

On The Spatial Modelling Of Biological Invasions, Tedi Ramaj

Electronic Thesis and Dissertation Repository

We investigate problems of biological spatial invasion through the use of spatial modelling. We begin by examining the spread of an invasive weed plant species through a forest by developing a system of partial differential equations (PDEs) involving an invasive weed and a competing native plant species. We find that extinction of the native plant species may be achieved by increasing the carrying capacity of the forest as well as the competition coefficient between the species. We also find that the boundary conditions exert long-term control on the biomass of the invasive weed and hence should be considered when implementing …

Conformational Dynamics And Aggregation Of Thermally Stressed Proteins Studied By Hydrogen/Deuterium Exchange Mass Spectrometry, Nastaran Nosrat Tajoddin

Electronic Thesis and Dissertation Repository

Proteins perform various biological functions, e.g., as enzymes or transporters. In addition to naturally occurring proteins, the use of protein therapeutic drugs for treating cancer and other diseases is a rapidly growing area. A thorough biophysical characterization of proteins and protein therapeutics opens the door to a more comprehensive understanding of their role in health and disease. This dissertation aims to expand the capabilities of an existing technique (Hydrogen Deuterium Exchange Mass Spectrometry, HDX-MS), which is widely used for probing protein structure and dynamics. Conventionally, HDX-MS experiments are performed as a function of labelling time. Here we aim to establish …

A Qualitative Look Into Repair Practices, Jumana Labib

Undergraduate Student Research Internships Conference

This research poster is based on a working research paper which moves beyond the traditional scope of repair and examines the Right to Repair movement from a smaller, more personal lens by detailing the 6 categorical impediments as dubbed by Dr. Alissa Centivany (design, law, economic/business strategy, material asymmetry, informational asymmetry, and social impediments) have continuously inhibited repair and affected repair practices, which has consequently had larger implications (environmental, economic, social, etc.) on ourselves, our objects, and our world. The poster builds upon my research from last year (see "The Right to Repair: (Re)building a better future"), this time pulling …

Producing And Measuring Oscillatory Shear In A Novel Microfluidic Chip, Sanaz Lordfard, Daniel Lorusso, Tamie L. Poepping, Hristo N Nikolov, Kayla Soon, Stephen Sims, Jeffrey Dixon, David Holdsworth

Undergraduate Student Research Internships Conference

Purpose: To demonstrate the effectiveness of a novel microfluidic device mimicking oscillatory blood flow, allowing cell biologists to examine how endothelial cells respond to a range of oscillatory shear stress levels.

Methods: The microfluidic chip consists of a circular-shaped reservoir, leading to a rectangular channel that is examined under a microscope. The plunger is connected to a speaker system and oscilloscope, allowing the plunger to apply a range of frequencies (5-60Hz) and voltages (5-10 V, leading to a variety in oscillation amplitudes) to the reservoir region. 1.1 um fluorescent particles diluted in distilled water were used for tracking. Processing was …

Exploring The Use Of Covellite As A Proxy For Corrosion Of Native Copper By Sulphur Reducing Bacteria, Manan K. Joshi

Undergraduate Student Research Internships Conference

We are analyzing the effect of sulphate reducing bacteria on native copper, and using that evidence to further support the initiative of having a deep geological repository to store nuclear material. Sulphate reducing bacteria are a concern for the deep geological repository as they cause the corrosion of regular copper. However native copper has gone billions of years without corrosion, which could either mean that it had not been exposed to sulphate reducing bacteria over the billions of years, or native copper is able to withstand corrosion despite the contact of sulphate reducing bacteria. We can find out by trying …

An Implementation Of Integrated Information Theory In Resting-State Fmri, Idan E. Nemirovsky

Electronic Thesis and Dissertation Repository

Integrated Information Theory (IIT) is a framework developed to explain consciousness, arguing that conscious systems consist of interacting elements that are integrated through their causal properties. In this study, we present the first application of IIT to functional magnetic resonance imaging (fMRI) data and investigate whether its principal metric, Phi, can meaningfully quantify resting-state cortical activity patterns. Data was acquired from 17 healthy subjects who underwent sedation with propofol, a short acting anesthetic. Using PyPhi, a software package developed for IIT, we thoroughly analyze how Phi varies across different networks and throughout sedation. Our findings indicate that variations in Phi …

A Generative-Discriminative Approach To Human Brain Mapping, Deepanshu Wadhwa

Electronic Thesis and Dissertation Repository

During everyday behaviours, the brain shows complex spatial patterns of activity. These activity maps are very replicable within an individual, but vary significantly across individuals, even though they are evoked by the same behaviour. It is unknown how differences in these spatial patterns relate to differences in behavior or function. More fundamentally, the structural, developmental, and genetic factors that determine the spatial organisation of these brain maps in each individual are unclear. Here we propose a new quantitative approach for uncovering the basic principles by which functional brain maps are organized. We propose to take an generative-discriminative approach to human …

Coevolution Of Hosts And Pathogens In The Presence Of Multiple Types Of Hosts, Evan J. Mitchell

Electronic Thesis and Dissertation Repository

How will hosts and pathogens coevolve in response to multiple types of hosts? I study this question from three different perspectives. First, I model a scenario in which hosts are categorized as female or male. Hosts invest resources in maintaining their immune system at a cost to their reproductive success, while pathogens face a trade-off between transmission and duration of infection. Importantly, female hosts are also able to vertically transmit an infection to their newborn offspring. The main result is that as the rate of vertical transmission increases, female hosts will have a greater incentive to pay the cost to …

Using An Analytical Approach Of The Kuramoto Model To Stimulate 3d Neural Activity Of The Stomach, Morteza Al Rabya

Undergraduate Student Research Internships Conference

No abstract provided.

Numerical Simulation Of Adaptive Metabolic Response To Anti-Angiogenic Treatment In Renal Cell Carcinoma, Saranya Varakunan

Undergraduate Student Research Internships Conference

Renal cell carcinoma, a malignant kidney cancer, is often treated using anti-angiogenic drugs to prevent the growth of blood vessels within the tumour. Although tumours initially respond to this treatment, they eventually develop resistance. This resistance is hypothesized to be caused by a switch to a symbiotic metabolism that allows cells to survive even with a low blood supply.

This project seeks to computationally model the transport of oxygen, lactate, and glucose within a tumour in order to examine how cancer metabolism adapts to changes in blood vessels.

Synthesis Of Nucleotide Prodrugs As Potential Antiviral Agents, Mohammed Attaelmanan

Undergraduate Student Research Internships Conference

No abstract provided.

Stable Hydrogen Isotopes Of Aquatic-Emergent Versus Terrestrial Insects In Southern Ontario, Celina Y. Tang

Undergraduate Student Research Internships Conference

Aquatic-emergent insects are vectors of both contaminants and nutrients, linking the aquatic system to the terrestrial system. Aquatic-emergent insects are high in omega-3 fatty acids that benefit terrestrial aerial insectivores, such as bats and birds. With aerial insectivores on a decline, a contributing factor could be a decrease in the quality of insects. We collected insects from lakeshore and inland locations in Southern Ontario. Insects sampled included bees, wasps, ants, beetles, caddisflies, craneflies, dragonflies, marchflies, mayflies, midges, other flies, and true bugs. Insects’ wings and powdered bodies were then analyzed for stable hydrogen isotopes (d²H) in order …

Investigation Of Shocked Basalts From Vargeão Dome And Vista Alegre: Implications For The Search For Life On Mars, Nikol Posnov

Electronic Thesis and Dissertation Repository

Impact craters represent excellent astrobiological targets for planetary exploration missions to Mars. The impact of an asteroid or comet into a crystalline, H₂O-bearing target may result in development of a hydrothermal system and increase the habitability of the substrate for the colonization of endolithic microorganisms. Given that Mars’ surface is covered by cratered basaltic rock, this study investigated target rocks and impact breccias from Vargeão Dome and Vista Alegre impact structures that formed in basalt in the Paraná Basin of Brazil.

Utilizing petrography and micro-X-ray diffraction (μXRD), the degree of shock metamorphism in plagioclase was quantitively determined. Measuring …

The Analysis Of Ginsenosides In Ginseng Garden Soil, Karina Marie Kaberi

Electronic Thesis and Dissertation Repository

American ginseng (Panax quinquefolius L.) produces natural products called ginsenosides. The biggest challenge Ontario commercial ginseng farmers face is ginseng replant disease. To understand the function of ginseng root exudates, ginsenoside accumulation and persistence over time were investigated. Currently, no reliable ginsenoside specific extraction method, characterizing the changes in soil chemistry exists. Ginsenoside extraction protocol optimization was required to determine how ginsenoside composition changed over time. Overall, protocol optimization resulted in a 30% increase in yield of ginsenosides compared to previous extraction protocols. In the ginseng gardens, ginsenoside accumulation occurs slowly and did not reach significantly measurable amounts until the …

Population And Evolution Dynamics In Predator-Prey Systems With Anti-Predation Responses, Yang Wang

Electronic Thesis and Dissertation Repository

This thesis studies the impact of anti-predation strategy on the population dynamics of predator-prey interactions. This work includes three research projects.

In the first project, we study a system of delay differential equations by considering both benefit and cost of anti-predation response, as well as a time delay in the transfer of biomass from the prey to the predator after predation. We reveal some insights on how the anti-predation response level and the biomass transfer delay jointly affect the population dynamics; we also show how the nonlinearity in the predation term mediated by the fear effect affects the long term …

Imaging Of Neurotransmitters And Small Molecules In Brain Tissues Using Laser Desorption/Ionization Mass Spectrometry Assisted With Zinc Oxide Nanoparticles., Chaochao Chen, Steven R Laviolette, Shawn N Whitehead, Justin B Renaud, Ken K-C Yeung

Chemistry Publications

Inorganic nanostructured materials such as silicon, carbon, metals, and metal oxides have been explored as matrices of low-background signals to assist the laser desorption/ionization (LDI) mass spectrometric (MS) analysis of small molecules, but their applications for imaging of small molecules in biological tissues remain limited in the literature. Titanium dioxide is one of the known nanoparticles (NP) that can effectively assist LDI MS imaging of low molecular weight molecules (LMWM). TiO₂ NP is commercially available as dispersions, which can be applied using a chemical solution sprayer. However, aggregation of NP can occur in the dispersions and the aggregated NP …

Experimental And Computational Observations Of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association., Jasmin Federizon, Conrard Giresse Tetsassi Feugmo, Wei-Chiao Huang, Xuedan He, Kazutoyo Miura, Aida Razi, Joaquin Ortega, Mikko Karttunen, Jonathan F Lovell

Chemistry Publications

Cobalt porphyrin phospholipid (CoPoP) can incorporate within bilayers to enable non-covalent surface-display of antigens on liposomes by mixing with proteins bearing a polyhistidine tag (his-tag); however, the mechanisms for how this occurs are poorly understood. These were investigated using the his-tagged model antigen Pfs25, a protein antigen candidate for malaria transmission-blocking vaccines. Pfs25 was found to associate with the small molecule aquocobalamin, a form of vitamin B12 and a cobalt-containing corrin macrocycle, but without particle formation, enabling comparative assessment. Relative to CoPoP liposomes, binding and serum stability studies indicated a weaker association of Pfs25 to aquocobalamin or cobalt nitrilotriacetic acid …

Reconstructing Carbon Dynamics Of Alpine And Temperate Zone Lakes Using Stable Isotopic Analysis, Rebecca M. Doyle

Electronic Thesis and Dissertation Repository

Lake sediments integrate signals from the catchment, atmosphere and water column, offering a unique window through which to view changes in the carbon cycle. Carbon dynamics in lakes are changing due to nitrogen loading and anthropogenic climate warming (ACW), threatening the water quality of lakes. This thesis identifies how the carbon dynamics of lakes have responded to anthropogenically-driven forcings by comparing pre- and post- AD 1850 records preserved in lake sediments. First, the carbon dynamics of Barry Lake (Ontario, Canada), a low-elevation temperate lake, are investigated. Effective moisture (the net of water inputs and evaporation) is reconstructed using the carbon …

Effects Of Oxidative Modifications On The Structure And Non-Canonical Functions Of Cytochrome C Studied By Mass Spectrometry, Victor Yin

Electronic Thesis and Dissertation Repository

The peroxidase activity of the mitochondrial protein cytochrome c (cyt c) plays a critical role in triggering programmed cell death, or apoptosis. However, the native structure of cyt c should render this activity impossible due to the lack of open iron coordination sites at its heme cofactor. Despite its key biological importance, the molecular mechanisms underlying this structure-function mismatch remain enigmatic. The work detailed in this dissertation fills this knowledge gap by using mass spectrometry (MS) to decipher the central role that protein oxidative modifications and their associated structural changes play in activating the peroxidase function of cyt c …

Computational Methods For Predicting Protein-Protein Interactions And Binding Sites, Yiwei Li

Electronic Thesis and Dissertation Repository

Proteins are essential to organisms and participate in virtually every process within cells. Quite often, they keep the cells functioning by interacting with other proteins. This process is called protein-protein interaction (PPI). The bonding amino acid residues during the process of protein-protein interactions are called PPI binding sites. Identifying PPIs and PPI binding sites are fundamental problems in system biology.

Experimental methods for solving these two problems are slow and expensive. Therefore, great efforts are being made towards increasing the performance of computational methods.

We present DELPHI, a deep learning based program for PPI site prediction and SPRINT, an algorithmic …