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Engaging Students In A Genetics Course-Based Undergraduate Research Experience Utilizing Caenorhabditis Elegans In Hybrid Learning To Explore Human Disease Gene Variants, Natalie Forte, Virginia Veasey, Bethany Christie, Amira Carter, Marli Hanks, Alan Holderfield, Taylor Houston, Anil Challa, Ashley Turner Nov 2023

Engaging Students In A Genetics Course-Based Undergraduate Research Experience Utilizing Caenorhabditis Elegans In Hybrid Learning To Explore Human Disease Gene Variants, Natalie Forte, Virginia Veasey, Bethany Christie, Amira Carter, Marli Hanks, Alan Holderfield, Taylor Houston, Anil Challa, Ashley Turner

Research, Publications & Creative Work

Genetic analysis in model systems using bioinformatic approaches provides a rich context for a concrete and conceptual understanding of gene structure and function. With the intent to engage students in research and explore disease biology utilizing the nematode Caenorhabditis elegans model, we developed a semester-long course-based undergraduate research experience (CURE) in a hybrid (online/in-person) learning environment—the gene-editing and evolutionary nematode exploration CURE (GENE-CURE). Using a combination of bioinformatic and molecular genetic tools, students performed structure-function analysis of disease-associated variants of uncertain significance (VUS) in human orthologs. With the aid of a series of workshop-style research sessions, students worked in teams …


Enzyme Kinetics Of Deoxyuridine Triphosphatase From Western Corn Rootworm, Carlos Riera‑Ruiz, Hideaki Moriyama Nov 2023

Enzyme Kinetics Of Deoxyuridine Triphosphatase From Western Corn Rootworm, Carlos Riera‑Ruiz, Hideaki Moriyama

School of Biological Sciences: Faculty Publications

Objective The Western corn rootworm (WCR), Diabrotica virgifera virgifera, is a highly adaptable insect pest that has evolved resistance to a variety of control strategies, including insecticides. Therefore, it is interesting to examine how housekeeping proteins in WCR have been changed under WCR-controlling strategies. In this study, we focused on one of such proteins in WCR, a ubiquitous enzyme 5’-triphosphate nucleotidohydrolase (dUTPase). In the thymidine synthetic pathway, dUTPase hydrolyzes deoxyuridine triphosphate (dUTP) and supplies the substrate, deoxyuridine monophosphate, for the thymidylate synthase (TS). It decreases the cellular content of uracil, reducing uracil misincorporation into DNA. Suppressing the dUTPase activity, …


Enzyme Kinetics Of Deoxyuridine Triphosphatase From Western Corn Rootworm, Carlos Riera‑Ruiz, Hideaki Moriyama Nov 2023

Enzyme Kinetics Of Deoxyuridine Triphosphatase From Western Corn Rootworm, Carlos Riera‑Ruiz, Hideaki Moriyama

School of Biological Sciences: Faculty Publications

Objective The Western corn rootworm (WCR), Diabrotica virgifera virgifera, is a highly adaptable insect pest that has evolved resistance to a variety of control strategies, including insecticides. Therefore, it is interesting to examine how housekeeping proteins in WCR have been changed under WCR-controlling strategies. In this study, we focused on one of such proteins in WCR, a ubiquitous enzyme 5’-triphosphate nucleotidohydrolase (dUTPase). In the thymidine synthetic pathway, dUTPase hydrolyzes deoxyuridine triphosphate (dUTP) and supplies the substrate, deoxyuridine monophosphate, for the thymidylate synthase (TS). It decreases the cellular content of uracil, reducing uracil misincorporation into DNA. Suppressing the dUTPase activity, …


Shell Pnw, Victoria B. Martinez Bruno, Amy C. Hirons Dr. Nov 2023

Shell Pnw, Victoria B. Martinez Bruno, Amy C. Hirons Dr.

Hirons Field Techniques

No abstract provided.


Blue Runner (Caranx Crysos) Neurocranium, Delaney Deinlein, Gabriel Droz, David Kerstetter Nov 2023

Blue Runner (Caranx Crysos) Neurocranium, Delaney Deinlein, Gabriel Droz, David Kerstetter

All Scans: Kerstetter Fisheries and Avian Ecology 3D Scan Series

Neurocranium from approximately 30 cm total length (TL) Blue Runner (Caranx crysos), collected from Dania Pier in 2023 by Charles Klinger.


Catfish Neurocranium, Fiona Smith, Juliana Ottens, David Kerstetter Nov 2023

Catfish Neurocranium, Fiona Smith, Juliana Ottens, David Kerstetter

All Scans: Kerstetter Fisheries and Avian Ecology 3D Scan Series

No abstract provided.


Effect Of Ploidy On Salinity And Temperature Tolerance In Early Life Stages Of The Eastern Oyster (Crassostrea Virginica), Christian Boudreaux, Jessica Pruett, Alexz Carpenter, Kristie Willett, Deborah Gochfeld Nov 2023

Effect Of Ploidy On Salinity And Temperature Tolerance In Early Life Stages Of The Eastern Oyster (Crassostrea Virginica), Christian Boudreaux, Jessica Pruett, Alexz Carpenter, Kristie Willett, Deborah Gochfeld

Honors Theses

The U.S. Gulf of Mexico contains the largest remaining wild oyster fishery in the world, but populations have declined in recent decades. A growing interest in off-bottom aquaculture that relies on triploid eastern oysters (Crassostrea virginica) has emerged in the Gulf region, yet these faster growing oysters suffer high mortality as adults during low salinity events (< 5 ppt) in warmer summer months. The combined effects of salinity and temperature stressors on early life stages of triploid oysters are unknown. Early life stages are particularly crucial to understand because triploid oysters do not occur naturally and must be reared in hatchery settings, requiring appropriate water conditions to yield the greatest survival and growth. Thus, we tested the effects of different temperatures (28oC and 32oC) and salinities (5, 10, and 15 ppt) on diploid and triploid oysters at three critical production stages: veliger, pediveliger, and spat. Veliger survival was significantly lower for triploids relative to diploid oysters at all experimental conditions, but triploid veligers had faster growth than diploids at 32oC and 15 ppt. Pediveliger settlement was not affected by ploidy type and only reduced at high temperature (32oC) and the lowest salinity (5 ppt). Diploid spat showed highest survival at 28oC and 15 ppt, while triploids survived best at 32oC and 15 ppt. Triploid spat attained greater shell height compared to diploids in our 6-day exposures, but growth decreased for both ploidies at lower salinities. At the salinity and temperature levels examined, diploid early life stages performed best at 28oC and 15 ppt, whereas triploids were more successful at 32oC and 15 ppt. A broader understanding of the combined effects of environmental stressors will improve the success of hatchery production yields and the resulting economic and environmental benefits of the oyster industry.


Atlantic Cutlassfish (Trichiurus Lepturus), Gabriela R. Ridings Ms., David Kerstetter Nov 2023

Atlantic Cutlassfish (Trichiurus Lepturus), Gabriela R. Ridings Ms., David Kerstetter

All Scans: Kerstetter Fisheries and Avian Ecology 3D Scan Series

No abstract provided.


Targeting Bet Proteins Downregulates Mir-33a To Promote Synergy With Pim Inhibitors In Cmml, Christopher T. Letson Nov 2023

Targeting Bet Proteins Downregulates Mir-33a To Promote Synergy With Pim Inhibitors In Cmml, Christopher T. Letson

USF Tampa Graduate Theses and Dissertations

Chronic Myelomonocytic Leukemia (CMML) is a rare myeloid malignancy with a dismal prognosis and no therapeutic options which are capable of altering the natural course of the disease. There remains a significant need for novel therapies that are able to meaningfully improve patient outcomes. In this study we explore the effectiveness of Bromodomain and Extra-Terminal domain protein inhibitor (BETi) combinations in CMML. Preclinical studies in myeloid neoplasms have demonstrated efficacy of BETi. However, BETi demonstrate poor single agent activity in clinical trials. Several studies suggest that combinations with other anti-cancer inhibitors may enhance the efficacy of BETi. To nominate BETi …


Discovery, Structure-Activity Relationship And In Vitro Anticancer Activity Of Small-Molecule Inhibitors Of The Protein-Protein Interactions Between Af9/Enl And Af4 Or Dot1l, Xin Li, Xiaowei Wu, Shenyou Nie, Jidong Zhao, Yuan Yao, Fangrui Wu, Chandra Bhushan Mishra, Md Ashraf-Uz-Zaman, Bala Krishna Moku, Yongcheng Song Nov 2023

Discovery, Structure-Activity Relationship And In Vitro Anticancer Activity Of Small-Molecule Inhibitors Of The Protein-Protein Interactions Between Af9/Enl And Af4 Or Dot1l, Xin Li, Xiaowei Wu, Shenyou Nie, Jidong Zhao, Yuan Yao, Fangrui Wu, Chandra Bhushan Mishra, Md Ashraf-Uz-Zaman, Bala Krishna Moku, Yongcheng Song

Faculty, Staff and Students Publications

Simple Summary

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene generate potent fusion oncogenes and cause acute myeloid leukemia or lymphocytic leukemia, which account for ~75% infant and 5–10% child/adult acute leukemia cases with a poor prognosis (5-year survival rates < 45%). Protein–protein interactions between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are critical to malignant gene expression and are therefore a potential drug target for cancer. Compound screening followed by medicinal chemistry studies identified several novel small-molecule inhibitors showing strong inhibition of these protein–protein interactions, significant suppression of characteristic gene expression, and robust cellular anticancer activities with negligible cytotoxicity. These compounds are useful chemical probes for biological studies of these protein–protein interactions, as well as pharmacological leads for further drug development against MLL-rearranged and other leukemias.

Abstract

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5–10% acute leukemias with poor clinical outcomes. Protein–protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC50 values as …


Brain Metastasis-Associated Fibroblasts Secrete Fucosylated Pvr/Cd155 That Induces Breast Cancer Invasion, Emma Adhikari Nov 2023

Brain Metastasis-Associated Fibroblasts Secrete Fucosylated Pvr/Cd155 That Induces Breast Cancer Invasion, Emma Adhikari

USF Tampa Graduate Theses and Dissertations

Breast cancer (BC) continues to be the most diagnosed cancer and the second leading cause of cancer deaths in women worldwide. High mortality, in most cancers, is due to metastasis; BC is the most common source of one of the deadliest forms of metastasis–brain metastasis (BM) in female. Patients with triple negative breast cancer (TNBC) exhibit the highest incidence of BM and poorest survival outcomes upon diagnosis with BM. The prognosis of breast cancer brain metastasis (BCBM) remains poor because the blood–brain barrier (BBB) prevents the uptake of drug substances, including chemotherapeutic agents, targeted agents, and toxins, from the brain. …


Individual And Population Age Impact Social Behavior And Network Structure In A Long-Lived Insect, P. A. Cook, R. A. Costello, Vincent A. Formica, E. D. Brodie Iii Nov 2023

Individual And Population Age Impact Social Behavior And Network Structure In A Long-Lived Insect, P. A. Cook, R. A. Costello, Vincent A. Formica, E. D. Brodie Iii

Biology Faculty Works

Social behaviors vary among individuals, and social networks vary among groups. Understanding the causes of such variation is important for predicting or altering ecological processes such as infectious disease outbreaks. Here, we ask whether age contributes to variation in social behavior at multiple levels of organization: within individuals over time, among individuals of different ages, among local social environments, and among populations. We used experimental manipulations of captive populations and a longitudinal dataset to test whether social behavior is associated with age across these levels in a long-lived insect, the forked fungus beetle (Bolitotherus cornutus). In cross-sectional analyses, …


A Telencephalon Cell Type Atlas For Goldfish Reveals Diversity In The Evolution Of Spatial Structure And Cell Types, Muhammad Tibi, Stav Biton Hayun, Hannah Hochgerner, Zhige Lin, Shachar Givon, Osnat Ophir, Tal Shay, Thomas Mueller, Ronen Segev, Amit Zeisel Nov 2023

A Telencephalon Cell Type Atlas For Goldfish Reveals Diversity In The Evolution Of Spatial Structure And Cell Types, Muhammad Tibi, Stav Biton Hayun, Hannah Hochgerner, Zhige Lin, Shachar Givon, Osnat Ophir, Tal Shay, Thomas Mueller, Ronen Segev, Amit Zeisel

Department of Biology Faculty Scholarship and Creative Works

Teleost fish form the largest group of vertebrates and show a tremendous variety of adaptive behaviors, making them critically important for the study of brain evolution and cognition. The neural basis mediating these behaviors remains elusive. We performed a systematic comparative survey of the goldfish telencephalon. We mapped cell types using single-cell RNA sequencing and spatial transcriptomics, resulting in de novo molecular neuroanatomy parcellation. Glial cells were highly conserved across 450 million years of evolution separating mouse and goldfish, while neurons showed diversity and modularity in gene expression. Specifically, somatostatin interneurons, famously interspersed in the mammalian isocortex for local inhibitory …


Background Acoustics In Terrestrial Ecology, Clinton D. Francis, Jennifer N. Phillips, Jesse R. Barber Nov 2023

Background Acoustics In Terrestrial Ecology, Clinton D. Francis, Jennifer N. Phillips, Jesse R. Barber

Biology Faculty Publications and Presentations

The way in which terrestrial organisms use the acoustic realm is fundamentally important and shapes behavior, populations, and communities, but how background acoustics, or noise, influence the patterns and processes in ecology is still relatively understudied. In this review, we summarize how background acoustics have traditionally been studied from the signaling perspective, discuss what is known from a receiver's perspective, and explore what is known about population- and community-level responses to noise. We suggest that there are major gaps linking animal physiology and behavior in noise to fitness; that there is a limited understanding of variation in hearing within and …


Development And Application Of Sem/Eds In Biological, Biomedical & Nanotechnological Research, Aniruddha Acharya Nov 2023

Development And Application Of Sem/Eds In Biological, Biomedical & Nanotechnological Research, Aniruddha Acharya

Faculty Publications - Biological Sciences

This comprehensive review discusses the development of scanning electron microscopy and the application of this technology in different fields such as biology, nanobiotechnology and biomedical science. Besides being a tool for high resolution imaging of surface or topography, the technology is coupled with analytical techniques such as energy dispersive spectroscopy for elemental mapping. Since the commercialization of the technology, it has developed manifold and currently very high-resolution nano scale imaging is possible by this technology. The development of FIB-SEM has allowed three-dimensional imaging of materials while the development of cryostage allows imaging of hydrated biological samples. Though variable pressure or …


Big Boned: How Fat Storage And Other Adaptations Influenced Large Theropod Foraging Ecology, Cameron Pahl, Luis A. Ruedas Nov 2023

Big Boned: How Fat Storage And Other Adaptations Influenced Large Theropod Foraging Ecology, Cameron Pahl, Luis A. Ruedas

Biology Faculty Publications and Presentations

Dinosaur foraging ecology has been the subject of scientific interest for decades, yet much of what we understand about it remains hypothetical. We wrote an agent-based model (ABM) to simulate meat energy sources present in dinosaur environments, including carcasses of giant sauropods, along with living, huntable prey. Theropod dinosaurs modeled in this environment (specifically allosauroids, and more particularly, Allosaurus Marsh, 1877) were instantiated with heritable traits favorable to either hunting success or scavenging success. If hunter phenotypes were more reproductively successful, their traits were propagated into the population through their offspring, resulting in predator specialists. If selective pressure favored scavenger …


Coordinated Regulation Of Myonuclear Dna Methylation, Mrna, And Mirna Levels Associates With The Metabolic Response To Rapid Synergist Ablation-Induced Skeletal Muscle Hypertrophy In Female Mice, Ahmed Ismaeel, Nicholas T. Thomas, Mariah Mccashland, Sebastian Edman, Johanna T. Lanner, Vandré C. Figueiredo, Christopher S. Fry, John J. Mccarthy, Yuan Wen, Kevin A. Murach, Ferdinand Von Walden Nov 2023

Coordinated Regulation Of Myonuclear Dna Methylation, Mrna, And Mirna Levels Associates With The Metabolic Response To Rapid Synergist Ablation-Induced Skeletal Muscle Hypertrophy In Female Mice, Ahmed Ismaeel, Nicholas T. Thomas, Mariah Mccashland, Sebastian Edman, Johanna T. Lanner, Vandré C. Figueiredo, Christopher S. Fry, John J. Mccarthy, Yuan Wen, Kevin A. Murach, Ferdinand Von Walden

Health, Human Performance and Recreation Faculty Publications and Presentations

The central dogma of molecular biology dictates the general flow of molecular information from DNA that leads to a functional cellular outcome. In skeletal muscle fibers, the extent to which global myonuclear transcriptional alterations, accounting for epigenetic and post-transcriptional influences, contribute to an adaptive stress response is not clearly defined. In this investigation, we leveraged an integrated analysis of the myonucleus-specific DNA methylome and transcriptome, as well as myonuclear small RNA profiling to molecularly define the early phase of skeletal muscle fiber hypertrophy. The analysis of myonucleus-specific mature microRNA and other small RNA species provides new directions for exploring muscle …


Yellowtail Snapper, Abigayle Groth, David Kerstetter Nov 2023

Yellowtail Snapper, Abigayle Groth, David Kerstetter

All Scans: Kerstetter Fisheries and Avian Ecology 3D Scan Series

No abstract provided.


Interactive Effects Of Increased Nestbox Temperature And Vitamin E On Nestling Growth Are Attenuated By Plasticity In Female Incubation Effort, Paige A. Duncan, Ashley M. Tauber, Scott K. Sakaluk, Charles F. Thompson Nov 2023

Interactive Effects Of Increased Nestbox Temperature And Vitamin E On Nestling Growth Are Attenuated By Plasticity In Female Incubation Effort, Paige A. Duncan, Ashley M. Tauber, Scott K. Sakaluk, Charles F. Thompson

Faculty Publications – Biological Sciences

In recent years, temperatures have increased globally, and nestlings of many bird species are likely regularly exposed to increased temperatures both pre- and post-natally. Even small increases in nest temperature during incubation affect offspring growth and survival in a variety of species, one cause of which is thought to be increased production of pro-oxidants in embryos and nestlings. Defences marshalled in response to this oxidative stress could, in turn, result in trade-offs that lead to reduced survival or growth. If so, any downstream negative effects on nestlings of increased ambient temperatures during incubation could be counteracted by increasing their antioxidant …


The Impacts Of Embryo Development And Asynchronous Hatching On Morphology, Growth, And Development Of Larval Burbot (Lota Lota)., Andrew J. Shapiro Nov 2023

The Impacts Of Embryo Development And Asynchronous Hatching On Morphology, Growth, And Development Of Larval Burbot (Lota Lota)., Andrew J. Shapiro

All NMU Master's Theses

Burbot (Lota lota) are native fish in Lake Superior and typically spawn during the winter under the ice or by migrating up rivers. The early life history of larval burbot, where they dispurse, how fast they develop, and what their survival rates have not been extensively studied. Asynchronous hatching is a strategy used by other cod species as a bet-hedging strategy to ensure that some larvae are hatched in more advantageous conditions in a varying environment. Asynchronous hatching has been documented in burbot, but the extent of the period and the impacts that asynchrony has on the development of …


Population Structure And Genetic Diversity Of The Socotra Cormorant (Phalacrocorax Nigrogularis), Noura Mabkhout Almansoori Nov 2023

Population Structure And Genetic Diversity Of The Socotra Cormorant (Phalacrocorax Nigrogularis), Noura Mabkhout Almansoori

Theses

The Socotra cormorants (Phalacrocorax nigrogularis) are regional endemic seabirds restricted to the Arabian Gulf, Gulf of Oman, and the Arabian Sea. This species is classified as vulnerable by the IUCN Red List. However, no population genetic study has been conducted on P. nigrogularis in their range, and population structure, gene flow and connectivity between colonies is unknown. Likewise, genetic diversity of this species has not yet been characterized. Thus, the aim of this thesis was to fill these gaps by inferring population structure, assessing gene flow and genetic diversity of Socotra cormorant colonies in their known distribution range. …


Anti Cancer Activity Of Rhus Coriaria (Sumac) Against 5-Fluorouracil-Resistant Colorectal Cancer Cells, Zohra Nausheen Nizami Nov 2023

Anti Cancer Activity Of Rhus Coriaria (Sumac) Against 5-Fluorouracil-Resistant Colorectal Cancer Cells, Zohra Nausheen Nizami

Theses

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths, both worldwide and in the UAE. 5-Fluorouracil (5-FU), a pyrimidine analogue, is a chemotherapeutic agent that is an integral component of chemotherapy regimens for CRC treatment. However, 5-FU resistance (intrinsic and/or acquired) inhibits their clinical efficacy. In recent years, there has been a growing popularity for plant-based cancer therapeutics, specifically using phytochemical compounds. Rhus coriaria (Sumac) is a Mediterranean plant whose fruits are used as a spice and medicinal herb. Extracts of Rhus coriaria fruits (RCE) have been reported to exhibit anti-cancer activity against breast cancer and CRC. In …


An Automated Respiratory Data Pipeline For Waveform Characteristic Analysis, Savannah Lusk, Christopher S Ward, Andersen Chang, Avery Twitchell-Heyne, Shaun Fattig, Genevera Allen, Joanna L Jankowsky, Russell S Ray Nov 2023

An Automated Respiratory Data Pipeline For Waveform Characteristic Analysis, Savannah Lusk, Christopher S Ward, Andersen Chang, Avery Twitchell-Heyne, Shaun Fattig, Genevera Allen, Joanna L Jankowsky, Russell S Ray

Faculty, Staff and Students Publications

Comprehensive and accurate analysis of respiratory and metabolic data is crucial to modelling congenital, pathogenic and degenerative diseases converging on autonomic control failure. A lack of tools for high-throughput analysis of respiratory datasets remains a major challenge. We present Breathe Easy, a novel open-source pipeline for processing raw recordings and associated metadata into operative outcomes, publication-worthy graphs and robust statistical analyses including QQ and residual plots for assumption queries and data transformations. This pipeline uses a facile graphical user interface for uploading data files, setting waveform feature thresholds and defining experimental variables. Breathe Easy was validated against manual selection by …


It’S All About Fishing: Robert Ellis Jenkins (1940-2023) And His Life Among Freshwater Fishes Of Virginia And The Redhorse Suckers, Eric J. Hilton Oct 2023

It’S All About Fishing: Robert Ellis Jenkins (1940-2023) And His Life Among Freshwater Fishes Of Virginia And The Redhorse Suckers, Eric J. Hilton

Southeastern Fishes Council Proceedings

Robert (Bob) Ellis Jenkins passed away in Salem, Virginia, on Wednesday, July 12, 2023. Bob was born February 9, 1940 in Brooklyn, New York. As a child, Bob took an early interest in natural history, and was a particularly avid fisherman. He attended Roanoke College (Salem, VA) as an undergraduate and entered into a Masters degree program at Virginia Tech (Blacksburg, VA), only to leave before finishing for a position at the NOAA Systematics Lab based at the Smithsonian Institution’s National Museum of Natural History. He eventually became faculty at his alma mater, Roanoke College, where he would spend virtually …


Big 5 Conservation Internship, Bernhard Riegl Oct 2023

Big 5 Conservation Internship, Bernhard Riegl

Trick to the Treat of Internships and Research

The Discover Eden Big 5 Ecology and Conservation course is located in South Africa. Through a series of first-hand experiences and lectures, one learns much about Conservation and what it really is. By working with Ecologists, Conservationists, and Veterinarians, you gain insight into these professions and what they entail


Evaluating The Utility Of S100a8/A9 As A Non-Invasive Biomarker, Leah Mellett Oct 2023

Evaluating The Utility Of S100a8/A9 As A Non-Invasive Biomarker, Leah Mellett

Arts & Sciences Graduate Student Theses and Dissertations

Biomarkers, a portmanteau of “biological markers”, are clinically relevant observations that can accurately and reproducibly indicate or predict patient outcomes. These objective measurements have vast clinical utility as they can aid clinicians with diagnoses, provide information about patient prognoses, and monitor changes in patient health statuses. While the discovery of several biomarkers are attributed to differential expression or concentration of genes or proteins within blood samples, biomarkers can be alternatively found in other bodily fluids or tissues depending on the associated condition. Recently, advances in urine proteomics have allowed for the identification of urine biomarkers that may eliminate the drawbacks …


Examining The Role Of Microglia In Diabetic Retinopathy: Phenotypes, Mechanisms, And Therapies, Charles W. Pfeifer Oct 2023

Examining The Role Of Microglia In Diabetic Retinopathy: Phenotypes, Mechanisms, And Therapies, Charles W. Pfeifer

Arts & Sciences Graduate Student Theses and Dissertations

Retinal microglia activation and function is a pivotal component of ocular disease pathology, but their involvement in diabetic retinopathy, a complex neurovascular complication of diabetes, remains unclear. The purpose of this thesis work is to thoroughly examine features of microglia activation in DR, identify mechanistic underpinnings of their contributions to neuroinflammatory features of disease pathogenesis, and assess immunotherapeutic targeting of microglia as a potential approach to treating early-stage DR. Here, we show that chronic hyperglycemia elicits morphological, ultrastructural, and transcriptional changes in retinal microglia during early-stage DR while other elements of the retinal neurovascular unit remain unperturbed. Through chronic ablation …


A Small-Molecule Inhibitor Of Topbp1 Exerts Anti-Myc Activity And Synergy With Parp Inhibitors, Fang-Tsyr Lin, Kang Liu, Lidija A Wilhelms Garan, Helena Folly-Kossi, Yongcheng Song, Shwu-Jiuan Lin, Weei-Chin Lin Oct 2023

A Small-Molecule Inhibitor Of Topbp1 Exerts Anti-Myc Activity And Synergy With Parp Inhibitors, Fang-Tsyr Lin, Kang Liu, Lidija A Wilhelms Garan, Helena Folly-Kossi, Yongcheng Song, Shwu-Jiuan Lin, Weei-Chin Lin

Faculty, Staff and Students Publications

We have previously identified TopBP1 (topoisomerase IIβ-binding protein 1) as a promising target for cancer therapy, given its role in the convergence of Rb, PI(3)K/Akt, and p53 pathways. Based on this, we conducted a large-scale molecular docking screening to identify a small-molecule inhibitor that specifically targets the BRCT7/8 domains of TopBP1, which we have named 5D4. Our studies show that 5D4 inhibits TopBP1 interactions with E2F1, mutant p53, and Cancerous Inhibitor of Protein Phosphatase 2A. This leads to the activation of E2F1-mediated apoptosis and the inhibition of mutant p53 gain of function. In addition, 5D4 disrupts the interaction of TopBP1 …


To What Extent Do Physiological Tolerances Determine Elevational Range Limits Of Mammals?, Jay F. Storz, Graham R. Scott Oct 2023

To What Extent Do Physiological Tolerances Determine Elevational Range Limits Of Mammals?, Jay F. Storz, Graham R. Scott

School of Biological Sciences: Faculty Publications

A key question in biology concerns the extent to which distributional range limits of species are determined by intrinsic limits of physiological tolerance. Here, we use common-garden data for wild rodents to assess whether species with higher elevational range limits typically have higher thermogenic capacities in comparison to closely related lowland species. Among South American leaf-eared mice (genus Phyllotis), mean thermogenic performance is higher in species with higher elevational range limits, but there is little among-species variation in the magnitude of plasticity in this trait. In the North American rodent genus Peromyscus, highland deer mice (Peromyscus maniculatus …


Ecological Correlates For Endemic And Threatened Amphibians In The Uluguru Nature Forest Reserve, Tanzania, Joseph M. Christopher, Wilirk Ngalason, John V. Lyakurwa Oct 2023

Ecological Correlates For Endemic And Threatened Amphibians In The Uluguru Nature Forest Reserve, Tanzania, Joseph M. Christopher, Wilirk Ngalason, John V. Lyakurwa

Tanzania Journal of Science

Information on habitat characteristics for endemic and threatened amphibians along the altitudinal gradient in the Uluguru Nature Forest Reserve (UNFR) is limited. We assessed habitat characteristics associated with the occurrence of endemic and threatened amphibians in the Uluguru Nature Forest Reserve between April and June 2022. Bucket pitfall traps, time-constrained audio-visual surveys, plots and opportunistic searching were used to study amphibians in 6 sites along elevational gradient from 600 m to 2100 m a.s.l. Eighteen amphibian species were recorded, thirteen of them being endemic to the Eastern Arc Mountains, two near-endemic and three widely distributed. Among the species recorded, seven …