Biology Commons^™

Relating Spontaneous Activity And Cognitive States Via Neurodynamic Modeling, Matthew Singh

Arts & Sciences Graduate Student Theses and Dissertations

Stimulus-free brain dynamics form the basis of current knowledge concerning functional integration and segregation within the human brain. These relationships are typically described in terms of resting-state brain networks—regions which spontaneously coactivate. However, despite the interest in the anatomical mechanisms and biobehavioral correlates of stimulus-free brain dynamics, little is known regarding the relation between spontaneous brain dynamics and task-evoked activity. In particular, no computational framework has been previously proposed to unite spontaneous and task dynamics under a single, data-driven model. Model development in this domain will provide new insight regarding the mechanisms by which exogeneous stimuli and intrinsic neural circuitry …

Thermodynamics And Conformational Heterogeneity Of Recbcd Binding To Dna Ends, Linxuan Hao

Arts & Sciences Graduate Student Theses and Dissertations

E. coli RecBCD is crucial in initiating repair of double stranded (ds) DNA breaks. It is a heterotrimeric helicase and nuclease complex possessing two ATPase motors, RecB and RecD, and a regulatory subunit without ATPase activity, RecC. The RecB subunit also contains a 30kDa nuclease domain (RecBNuc) that, according to published structural data, is situated over 60Å away from the site of dsDNA binding. Surprisingly, we have shown in previous studies that deletion of RecBNuc to form RecBΔNucCD affects its dsDNA unwinding properties. The mechanism by which RecBNuc influences RecBCD dsDNA unwinding is unclear. In this thesis, equilibrium binding techniques, …

Understand And Predict Microbiome And Resistome Dynamics In Response To Perturbations Across Diverse Populations And Environments, Manish Boolchandani

Arts & Sciences Graduate Student Theses and Dissertations

Complex microbial communities are at the interface of human, animal and environment interconnected ecosystem, where they can move within and between these entities. These microbial communities are mostly beneficial, maintaining the host health and homeostatic state. However, these communities can also serve as reservoirs of antibiotic resistance (AR) genes that may disseminate to pathogen bacteria, compromising the treatment options. Like other microbial communities, human gut microbiome is highly dynamic and can get acutely perturbed with the changes in the habitat, diet, lifestyle and disease. A perturbed gut community structure has profound impact on the host health and physiology. Use of …

Functional Interrogation Of Jak2 And Asxl1 Mutations In Myeloproliferative Neoplasms, Taylor Brost Collins

Arts & Sciences Graduate Student Theses and Dissertations

JAK2 V617F is the most frequent mutation found in myeloproliferative neoplasms (MPNs), with 50-60% of myelofibrosis (MF) patients harboring this mutation. Mutations in ASXL1 often co-occur with JAK2 V617F and are associated with decreased survival and increased risk of transformation to secondary acute myeloid leukemia. How mutant ASXL1 contributes to the MPN disease phenotype and confers poor prognosis is not fully understood. Asxl1 mutation knock-in mouse models present with a relatively modest phenotype, following a long latency period and ASXL1 mutations have not been modeled in combination with JAK2 V617F. The field lacks human model systems that focus on how …

Ascension And Adhesion Of Uropathogenic Escherichia Coli During Pyelonephritis, Lisa Kristine Mclellan

Arts & Sciences Graduate Student Theses and Dissertations

The ability of uropathogenic Escherichia coli (UPEC) to successfully establish an infection within the urinary tract relies on the pathogen to be able to navigate the complex interactions between pathogen and host. During a urinary tract infection (UTI), UPEC must ascend, adhere, and form bacterial communities in various infection niches, from the bladder (cystitis) to the kidneys (pyelonephritis). Each of these steps is critical for bacterial survival, and host and pathogen factors required at each stage can vary depending on host sex and anatomic niche. Preclinical modeling of pyelonephritis and sex effects on UTI has been limited due to the …

The Roles Of Plasmepsins Ix And X In Malaria Parasite Biology, Armiyaw Sebastian Nasamu

Arts & Sciences Graduate Student Theses and Dissertations

Proteases of the malaria parasite Plasmodium falciparum have been targeted for drug discovery for decades. The P. falciparum genome encodes ten aspartic proteases called plasmepsins, which are involved in diverse cellular processes. In this work we address the roles of two of these plasmepsins, plasmepsins IX and X (PM IX and X), the two least studied aspartic proteases in blood stage malaria parasites till date. We explore the essentiality of these proteases in parasite development, attempt to identify their substrates and the ability to drug them. We show that PM IX is essential for erythrocyte invasion, acting on rhoptry secretory …

Protein Synthesis Adaptation To The Au-Rich Transcriptome Of Plasmodium Falciparum, Jessey Lee Erath

Arts & Sciences Graduate Student Theses and Dissertations

The process of protein synthesis whereby a messenger RNA is decoded into an amino acid chainis conserved among the domains. Fastidious protein synthesis is necessary for organism survival. However, exceptions negatively affecting the mRNA translation cycle – inadvertently or by design – may occur. Polyadenosine tracts are one such motif causing ribosomal stalling and frameshifting in almost all organisms tested thus far; save Plasmodium spp. Thus, with ~60% of their protein-coding genome harboring polyadenosine tracts, the elucidation of such paradigm-breaking adaptations enabling Plasmodium spp. to translate this typically problematic motif without issue is salient from both basic science and clinical …

Prodrug Activation In Staphylococci And The Implications For Antimicrobial Development, Justin J. Miller

Arts & Sciences Graduate Student Theses and Dissertations

Antibiotic resistance is an increasing concern for global health care, with some estimates suggesting that 10 million people will die from antibiotic resistant infections in the year 2050. Fueling this prospect, few antimicrobials are being actively developed and recently commercial entities have fled from the development of new anti-infectives. New antimicrobials and drug development strategies are urgently needed to revitalize this critical pipeline. While many putative antibiotics demonstrate promising in vitro potency, they routinely fail in vivo due to poor drug-like properties (e.g. oral bioavailability, serum-half life, toxicity) resulting in overly expensive drug development pipelines. Fortunately, drug-like properties can be …

Identify Genetic And Epigenetic Abnormalities Associated With Therapeutic Vulnerability In Human Cancers, Wen-Wei Liang

Arts & Sciences Graduate Student Theses and Dissertations

Human cancer is a complex and dynamic disease with mutational, spatial, and temporal heterogeneity. There has been a concerted effort to address the heterogeneity by profiling large-scale multiomic datasets with an emphasis on abnormalities such as DNA mutations at coding regions and structural variants. However, a systematic analysis of alterations at “dark matter” is lacking – including DNA slippage events at microsatellite sequences, gene fusions arising from genomic rearrangements, and aberrant DNA methylations at promoter regions. This dissertation focus on developing data-driven computational analysis pipelines to study the patterns of microsatellite instability, gene fusions, and aberrant DNA methylation, and their …

Investigating The Integration-Independent Role Of Hiv-1 In In The Viral Life Cycle, Jennifer Elliott

Arts & Sciences Graduate Student Theses and Dissertations

Human immunodeficiency virus type 1 (HIV-1) relies on a handful of essential enzymes for replication. Among these, the viral integrase enzyme (IN) plays a pivotal role in the viral life cycle by catalyzing the integration of the reverse-transcribed viral DNA into the host chromosome. While integration is the canonical role of IN, new research has uncovered an additional vital role for IN during virion morphogenesis. This dissertation elucidates how IN contributes to proper packaging of the viral RNA genome (vRNA) within the viral capsid and examines the fate of improperly formed viral particles in target cells.IN is proposed to mediate …

Targeting The Phgdh-Mtor Metabolic Axis In Osteosarcoma, Richa Rathore

Arts & Sciences Graduate Student Theses and Dissertations

Altering cellular energy metabolism has been highlighted as one of the emerging hallmarks of cancer. The reprogramming of bioenergetic pathways towards enhanced glycolysis, rather than the mitochondrial oxidative phosphorylation indicative of normal cells, results in increased biomass production and is associated with the activation of various oncogenes. The increased or decreased expression of key metabolic enzymes has been identified as a potential family of biomarkers that could serve as the targets for novel metabolic-based therapies in cancer.The serine, glycine, and one-carbon (SGOC) metabolism pathway consists of a series of enzymes and metabolites that drive protein and lipid production, enhanced DNA …

Of Mice And Toddlers: A Cross-Species Investigation Of The Social Motivation Theory Of Autism, Claire Weichselbaum

Arts & Sciences Graduate Student Theses and Dissertations

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social impairments and restricted, repetitive behaviors. Despite its growing prevalence, ASD remains poorly understood. One explanation for its social symptoms that has gained prominence in recent years is the Social Motivation Theory, which proposes a reduced motivation for social engagement as the underlying cause of impaired social functioning in ASD. While typically developing individuals find social interaction inherently rewarding, this theory suggests that people who develop ASD do not experience the same attraction to social stimuli and therefore miss out on critical social learning opportunities, hampering the development of …

Computational Analysis Of Non-Cpg Dna Methylation In The Mammalian Nervous System, Dennis Yawen Wu

Arts & Sciences Graduate Student Theses and Dissertations

Noncanonical forms of DNA methylation, especially non-CpG DNA methylation, play essential roles in the neuronal epigenome, and have only recently begun to be characterized. While most DNA methylation within mammals is found in a CG context and maintained by DNMT1, neurons contain uniquely high levels of non-CpG methylation, such that the total amounts of methylation in non-CpG contexts equals or surpasses the total amounts of methylation in CG contexts. Non-CpG methylation, unlike CpG methylation, cannot be maintained by DNMT1, and must be established by the de novo methyltransferase DNMT3A.One unique characteristic of non-CpG methylation compared to canonical CpG methylation is …

Genome-Wide Association Study Identifies New Loci Associated With Risk Of Hbv Infection And Disease Progression, Zheng Zeng, Liu Hankui, Xu Huifang, Lu Haiying, Yu Yanyan, Xu Xiaoyuan, Yu Min, Zhang Tao, Tian Xiulan, Xi Hongli, Guan Liping, Zhang Jianguo, Stephen James O'Brien

Biology Faculty Articles

Background: Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes.

Results: In order to discover new susceptibility genes for HBV-related outcomes, we conducted a genome-wide association study in 1031 Chinese participants, including 275 HBV clearance subjects, 92 asymptomatic persistence infection carriers (ASPI), 93 chronic hepatitis B patients (CHB), 188 HBV-related decompensated cirrhosis patients (DC), 214 HBV-related hepatocellular carcinoma patients (HCC) and 169 healthy controls (HC). In the case-control study, we observed novel locus significantly associated with CHB …

Diversity And Equity During Covid 19: An Analysis Of Student Attitude And Understanding In Pathophysiology, Sowmya Anjur

Faculty Publications & Research

To increase student engagement and reduce frustration over grades, data is being collected in my Pathophysiology classes on specific assessment questions which require students to think and apply what they have learned to answer assessment questions (“transfer” questions). These questions are being administered both before and after students have completed specific modules to assess their attitude and understanding of the material. Data is also being collected on student study habits before and after specific assessments for correlation with their scores on “transfer” questions. It is hoped to reduce student frustration over grades by analyzing their behavior and improving their understanding.

A Record Of Vapour Pressure Deficit Preserved In Wood And Soil Across Biomes, Adrian Broz, Gregory J. Retallack, Toby M. Maxwell, Lucas C.R. Silva

Biology Faculty Publications and Presentations

The drying power of air, or vapour pressure deficit (VPD), is an important measurement of potential plant stress and productivity. Estimates of VPD values of the past are integral for understanding the link between rising modern atmospheric carbon dioxide (pCO₂) and global water balance. A geological record of VPD is needed for paleoclimate studies of past greenhouse spikes which attempt to constrain future climate, but at present there are few quantitative atmospheric moisture proxies that can be applied to fossil material. Here we show that VPD leaves a permanent record in the slope (S) of least-squares …

Intragenic Dna Methylation Regulates Insect Gene Expression And Reproduction Through The Mbd/Tip60 Complex, Guanfeng Xu, Hao Lyu, Yangqin Yi, Yuling Peng, Qili Feng, Qisheng Song, Chengcheng Gong, Xuezhen Peng, Subba Reddy Palli, Sichun Zheng

Entomology Faculty Publications

DNA methylation is an important epigenetic modification. However, the regulations and functions of insect intragenic DNA methylation remain unknown. Here, we demonstrate that a regulatory mechanism involving intragenic DNA methylation controls ovarian and embryonic developmental processes in Bombyx mori. In B. mori, DNA methylation is found near the transcription start site (TSS) of ovarian genes. By promoter activity analysis, we observed that 5′ UTR methylation enhances gene expression. Moreover, methyl-DNA-binding domain protein 2/3 (MBD2/3) binds to the intragenic methyl-CpG fragment and recruits acetyltransferase Tip60 to promote histone H3K27 acetylation and gene expression. Additionally, genome-wide analyses showed that the peak …

Effect Of Temperature On Heart Rate For Phaenicia Sericata And Drosophila Melanogaster With Altered Expression Of The Trpa1 Receptors, Nicole T. Marguerite, Jate Bernard, Douglas A. Harrison, David Harris, Robin L. Cooper

Biology Faculty Publications

The transient receptor potential (TrpA—ankyrin) receptor has been linked to pathological conditions in cardiac function in mammals. To better understand the function of the TrpA1 in regulation of the heart, a Drosophila melanogaster model was used to express TrpA1 in heart and body wall muscles. Heartbeat of in intact larvae as well as hearts in situ, devoid of hormonal and neural input, indicate that strong over-expression of TrpA1 in larvae at 30 or 37 °C stopped the heart from beating, but in a diastolic state. Cardiac function recovered upon cooling after short exposure to high temperature. Parental control larvae (UAS-TrpA1) …

Philibaetis Gen. Nov., A New Genus From The Philippines (Ephemeroptera, Baetidae), Thomas Kaltenbach, Jhoana M. Garces, Jean-Luc Gattolliat

Biology Faculty Publications

Investigations of type material and new material from the Philippines (Luzon) revealed that Baetis luzonensis Müller-Liebenau, 1982 and B. realonae Müller-Liebenau, 1982 do not belong to Baetis Leach, 1815. A new genus, Philibaetis gen. nov., is described to accommodate both species and both are re-described based on larvae. The new genus is characterised by having a rectangular labrum with a submarginal row of long, simple setae on the dorsal surface and ventrally on lateral margins long, simple, spine-like setae, on anterolateral margins long, feathered setae and medially long, bifid setae and a partial, submarginal row of lanceolate setae. Both mandibles …

Cyclin-Dependent Kinase 1 And Aurora Kinase Choreograph Mitotic Storage And Redistribution Of A Growth Factor Receptor, C. D. Cota, M. S. Dreier , '20, W. Colgan, A. Cha, Twan Sia , '21, Bradley Justin Davidson , '91

Biology Faculty Works

Endosomal trafficking of receptors and associated proteins plays a critical role in signal processing. Until recently, it was thought that trafficking was shut down during cell division. Thus, remarkably, the regulation of trafficking during division remains poorly characterized. Here we delineate the role of mitotic kinases in receptor trafficking during asymmetric division. Targeted perturbations reveal that Cyclin-dependent Kinase 1 (CDK1) and Aurora Kinase promote storage of Fibroblast Growth Factor Receptors (FGFRs) by suppressing endosomal degradation and recycling pathways. As cells progress through metaphase, loss of CDK1 activity permits differential degradation and targeted recycling of stored receptors, leading to asymmetric induction. …

The Role Of Neuropilin-1 In Covid-19, Bindu Mayi, Jillian A. Leibowitz, Arden T. Woods, Katherine A. Ammon, Alphonse E. Liu, Aarti Raja

Biology Faculty Articles

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at …

Genome-Wide Discovery Of Natural Variation In Pre-Mrna Splicing And Prioritising Causal Alternative Splicing To Salt Stress Response In Rice, Huihui Yu, Qian Du, Malachy Campbell, Bin Yu, Harkamal Walia, Chi Zhang

School of Biological Sciences: Faculty Publications

• Pre-mRNA splicing is an essential step for the regulation of gene expression. In order to specifically capture splicing variants in plants for genome-wide association studies (GWAS), we developed a software tool to quantify and visualise Variations of Splicing in Population (VASP).
• VASP can quantify splicing variants from short-read RNA-seq datasets and discover genotype-specific splicing (GSS) events, which can be used to prioritise causal pre-mRNA splicing events in GWAS. We applied our method to an RNA-seq dataset with 328 samples from 82 genotypes from a rice diversity panel exposed to optimal and saline growing conditions.
• In total, 764 significant GSS events …

Complete Genome Sequence Of Geobacter Sp. Strain Feam09, A Moderately Acidophilic Soil Bacterium, Pooja Yadav, Sanjay Antony-Babu, Erin Hayes, Olivia M. Healy, Donald Pan, Wendy H. Yang, Whendee L. Silver, Christopher L. Anderson, Adam Voshall, Samodha C. Fernando, Etsuko N. Moriyama, Joshua R. Herr, Karrie A. Weber

School of Biological Sciences: Faculty Publications

A moderately acidophilic Geobacter sp. strain, FeAm09, was isolated from forest soil. The complete genome sequence is 4,099,068 bp with an average GC content of 61.1%. No plasmids were detected. The genome contains a total of 3,843 genes and 3,608 protein-coding genes, including genes supporting iron and nitrogen biogeochemical cycling.

A Population Dynamics Tipping Point For Aging As A Cause Of Adult Death, Andrea Scharf

Biological Sciences Faculty Research & Creative Works

Populations are a fundamental level of biological organization that poses major challenges for analysis. Individual traits that influence development, diapause, reproduction, aging, and lifespan interact in complex ways to determine birth and death. Birth and death drive population dynamics and determine whether a population survives or is doomed for extinction. However, we lack a deep understanding of the relationships between individual traits and population dynamics, a major challenge in the emerging field of ecology-development (eco-devo). Here we establish a laboratory ecosystem using the model organism C. elegans and a computational simulation that realistically models the laboratory ecosystem. We used these …

Experimental Use Of Drosophila To Model Proliferation Of Sars-Cov-2 Infected Cells, Valerie Wicks

Undergraduate Honors College Theses 2016-

Drosophila have been vectors for scientific research since the beginning of the 20th century. Their successful use within experiments that investigated mendelian genetics inspired their continuous application to biological research. This includes topics that detailed what is now known as innate immunity. The innate immune system of Drosophila is a first line of defense against pathogens. Innate immunity has been extensively researched and has reserved responses between Drosophila and mammals. Specifically, Drosophila have been experimentally targeted to draw conclusions on human infecting viruses such as Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus (SARS-Cov-1). Such experiments modeled viral …

Acetaminophen Potentiates Fear: Comparing Evaluations Of Ancestral And Modern Threats, Andrew C. Gallup, Brianda K. L. Gagnon, Gillian Perry, Omar T. Eldakar

Biology Faculty Datasets

No abstract provided.

Improved De Novo Alignment Of A Girardia Dorotocephala Ma-C2 (2n = 24) Transcriptome, Labib Rouhana, J F. Ryan, Eugene M. P. Almazan

Biological Sciences Faculty Publications

Improved De novo alignment of a Girardia dorotocephala MA-C2 (2n = 24) transcriptome.

Environment–Host–Microbial Interactions Shape The Sarraceniapurpurea Microbiome At The Continental Scale, Zachary B. Freedman, Alicia Mcgrew, Benjamin Baiser, Mathilde Besson, Dominique Gravel, Timothée Poisot, Sydne Record, Lauren B. Trotta, Nicholas J. Gotelli

Biology Faculty Research and Scholarship

The importance of climate, habitat structure, and higher trophic levels on microbial diversity is only beginning to be understood. Here, we examined the influence of climate variables, plant morphology, and the abundance of aquatic invertebrates on the microbial biodiversity of the northern pitcher plant Sarracenia purpurea. The plant's cup‐shaped leaves fill with rainwater and support a miniature, yet full‐fledged, ecosystem with a diverse microbiome that decomposes captured prey and a small network of shredding and filter‐feeding aquatic invertebrates that feed on microbes. We characterized pitcher microbiomes of 108 plants sampled at 36 sites from Florida to Quebec. Structural equation …

The Geodiv R Package: Tools For Calculating Gradient Surface Metrics, Annie C. Smith, Kyla M. Dahlin, Sydne Record, Jennifer K. Costanza, Adam M. Wilson, Phoebe L. Zarnetske

Biology Faculty Research and Scholarship

The geodiv r package calculates gradient surface metrics from imagery and other gridded datasets to provide continuous measures of landscape heterogeneity for landscape pattern analysis. geodiv is the first open-source, command line toolbox for calculating many gradient surface metrics and easily integrates parallel computing for applications with large images or rasters (e.g. remotely sensed data). All functions may be applied either globally to derive a single metric for an entire image or locally to create a texture image over moving windows of a user-defined extent. We present a comprehensive description of the functions available through geodiv. A supplemental vignette provides …

The Effects Of Endocrine Disrupting Chemicals On Plants, Christian Mathew Pridemore

Theses, Dissertations and Capstones

Endocrine disrupting chemicals (EDCs) are a diverse group of chemicals which can have a detrimental effect on human health, affecting any physiological body system sensitive to hormonal changes. Human exposure to EDCs is inevitable due to their prevalence in modern living; EDCs are integral compounds found in everyday items with which humans interact and ingest. These, along with other indirect avenues leading to EDC exposure, pose a threat to both human health and to the health of wildlife and agricultural environments. Studies on the effects of EDCs on plants can be substantially informative and necessary for progress towards solving the …