Cell and Developmental Biology Commons^™

Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl

Electronic Theses and Dissertations

Cleft palate is a common birth defect. Etiologic mechanisms of palate cleft include defects in palate morphogenesis, mandibular growth, or spontaneous fetal mouth movement. Cleft palate linked to deficient fetal mouth movement has been demonstrated directly only in a single experimental model of loss of neurotransmission. Here, using retinoid deficient mouse embryos, we demonstrate directly for the first time that deficient fetal mouth movement and cleft palate occurs as a result of mis-patterned development of pharyngeal peripheral nerves and cartilages. Retinoid deficient embryos were generated by inactivation of retinol dehydrogenase 10 (Rdh10), which is critical for production of …

Embryonic Lethality Of Cranial Neural Crest Deletion Of Cdc73, Lilia Shen

Honors Scholar Theses

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a disease characterized by parathyroid tumors, renal cysts or tumors, uterine tumors, and ossifying jaw fibromas. The cause of this syndrome is linked to a tumor suppressor gene called Cdc73, which encodes the protein product parafibromin. The loss of proper expression of Cdc73/parafibromin is implicated in the development of the tumors typical of HPT-JT, although the exact mechanisms of tumorigenesis are unclear. In particular, not much is understood about the development of ossifying fibromas (OF) of the jaw in this syndrome. OF is a benign bone neoplasm that can affect the mandible and …

The Role And Regulation Of Alternative Polyadenylation In The Dna Damage Response, Michael R. Murphy

Dissertations, Theses, and Capstone Projects

Cellular homeostasis is achieved by the dynamic flux in gene expression. Post-transcriptional regulation of coding and non-coding RNA offers a fast method of adapting to a changing cellular environment, including deadenylation, microRNA (miRNA) pathway, and alternative polyadenylation (APA). In this dissertation, I explored some of the mechanisms involved in the post-transcriptional regulation of gene expression. The main hypothesis in these studies is that a single APA event after DNA damage is governed by specific conditions and factors outside of current known regulators of APA, and that the resultant transcript has a role in the DNA damage response (DDR). My aims …

Context Dependent Roles Of Mdmx (Mdm4) And Mdm2 In Breast Cancer Proliferation And Circulating Tumor Cells, Chong Gao

Dissertations, Theses, and Capstone Projects

Many human breast cancers overexpress the E3 ubiquitin ligase MDM2 and its homolog MDMX. Expression of MDM2 and MDMX occurs in both estrogen receptor α positive (ER+) and triple negative breast cancer (TNBC). We and others have reported that estrogen activated MDM2 strongly promotes proliferation in ER+ T47D breast cancer cells in a p53-independent manner. Whether MDM2 elicits in vivo p53-independent proliferative functions in T47D breast cancer cells has not been determined. Furthermore it has been shown that ectopic expression of MDM2 targets E-Cadherin for degradation thus leading to increased cell migration and invasion. Therefore we assessed the in vivo …

The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud

Dissertations, Theses, and Capstone Projects

Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death are …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Thiol-Based Misfolding: Linking Redox Balance To Cytosolic Proteostasis, Ford Amy

Dissertations and Theses (Open Access)

The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants and xenobiotics. Cysteine-containing proteins are especially at risk as the thiol side chain is subject to oxidation, adduction and chelation by thiol-reactive compounds. All of these thiol-modifiers have been demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. However, endogenous targets of thiol stress toxicity responsible for these outcomes are largely unknown. Furthermore, I hypothesize proteins identified as redox-active are prone to misfolding and aggregation by thiol-specific …

Cross-Presentation Is A Source Of Tumor Antigens For Multiple Myeloma Immunotherapy, Alexander A. Perakis

Dissertations and Theses (Open Access)

Cross-presentation is an essential bridge between the innate and adaptive arms of the immune system where antigen presenting cells (APCs) prime cytotoxic T cell responses. We have recently identified cross-presentation as a mechanism by which solid tumors present exogenous antigens. We therefore hypothesized that multiple myeloma would be capable of cross-presentation as these cells are derived from B cells, known APCs. We explored the capacity of multiple myeloma to cross-present PR1, a human leukocyte antigen (HLA)-A2 nonameric peptide that is derived from neutrophil elastase (NE) and proteinase 3 (P3), and the ability to treat multiple myeloma using PR1-targeting immunotherapies. Here …

John's "Embryonic Stem Cell Research: Re-Explored Considering Scientific, Philosophical And Theological Understanding Of Human Life" (Book Review), Joseph Baumstarck Jr.

The Christian Librarian

No abstract provided.

Evaluating The Potential Of Repurposing Commercially Available Drugs For The Treatment Of Viral Infections, Brennan Connor Mcewan

Undergraduate Honors Capstone Projects

Viral infections that are often overlooked as common seasonal illnesses such as influenza can rapidly become a public threat. They threaten society as new, more dangerous strains of these common viruses emerge and as strains develop resistance to current vaccines and antiviral treatments (Kochanek, Murphy, Xu, & Tejada-Vera, 2014). To combat this, the development of antiviral treatments with novel mechanisms of action is essential. Repurposing drugs instead of developing new drugs can save years of development time and hundreds of millions of dollars (DiMasi, Hansen, & Grabowski, 2003). To support the effort to discover drugs with unique mechanisms of action, …

Cellular Localization Of Rad51d Mutant Proteins And The Application Of Art To Increase Scientific Literacy In America, Claire L. Chabot

Senior Theses

Ovarian cancers are the leading cause of death from cancer of the female reproductive system. Approximately 50% of ovarian cancers have defects in the homologous recombination (HR) DNA repair pathway that is required for the repair of DNA double-stranded breaks. The status of HR genes, such as BRCA1, BRCA2, and the RAD51 family, contributes to ovarian cancer development as well as treatment decisions regarding chemotherapy, radiation, and immunotherapy. The overarching goal of this project is to identify new insights into HR that can integrate with Precision Medicine Initiatives and align with the goals of the Cancer Moonshot 2020 Program. I …

Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey

Biology ETDs

Properly executed cell division is crucial to development, maintenance, and longevity of multicellular organisms. Defects in both symmetric and asymmetric divisions can lead to improper developmental patterning, as well as genomic instability, disruption of tissue homeostasis, and cancer. Our research focuses on how regulators orchestrate proper cell divisions. Mushroom Body Defect (Mud) is one such regulator, and here we describe how Mud is regulated via the Hippo signaling pathway kinase Warts (Wts), showing Wts phosphorylates Mud to enhance interaction with the polarity protein Partner of Inscuteable, promoting spindle orientation activity. We next focus on another regulator, Shortstop (Shot), describing a …

Enhancing Immunotherapeutic Interventions For Treatment Of Chronic Lymphocytic Leukemia, Kamira K. Maharaj

USF Tampa Graduate Theses and Dissertations

Chronic lymphocytic leukemia (CLL) is the most common leukemia in developed countries. It is characterized by the accumulation of CD5+ B lymphocytes in the peripheral blood, bone marrow, and lymphoid tissues of affected patients. Patients experience lymphadenopathy, fatigue, and are severely immunocompromised. Management of disease and symptoms is possible with chemo-immunotherapy for higher risk patients; however, CLL remains incurable unless bone marrow transplant is performed. Identification of novel targets and optimization of current therapeutics is therefore still necessary. The new targeted therapies are at the forefront of development for CLL treatment, but it remains challenging to maximize their efficacies while …

Combating Drug Resistance - Comparison Of The Antibiotic Effect Of Hydrastis Canadensis Extract And Pure Berberine Via Minimum Inhibitory Concentration Assay, William Luke Scott, Timothy D. Trott

Research in Biology

Herbal medicines are a melee of complex organic chemicals, making it difficult to ascertain their direct mechanism of action. In contrast to mainstream pharmaceuticals, it is argued that herbal medicines are effective because of multiple constituents working synergistically. The complexity of herbal medicines may give them advantages over simpler pharmaceuticals in combating antibiotic resistant microbes, but these advantages can be difficult to quantitate. Popular literature frequently espouses the healing properties of herbal medicines, but many of these claims are not scientifically supported. Many gains could be realized in public health and medicine if more research was aimed at validating / …

X-Inactivation And Epigenetics, Serena Weston

Thinking Matters Symposium Archive

To prevent abnormal development caused by expressing both X chromosomes, female mammals inactivate one of their X chromosomes using an epigenetic process called dosage compensation. This literature review examines how X chromosome inactivation (XCI) occurs during the formation and development of an embryo. This condensation of DNA is marked by histone tail modifications, DNA methylation, and the arrival of structural proteins resulting in extraordinarily stable heterochromatin. X-inactivation is regulated in cis by the X-inactivation center (Xic) that contains the Xist gene and its antisense gene, Tsix. On one X chromosome, Xist RNA is expressed and coats the center of the …

The Phytoremediative Effects Of Coriandrum Sativum In Lead Contaminated Soil, Sierra D. Garrett, Timothy Trott

Research in Biology

Environmental exposure to heavy metals such as lead pose a significant health threat. The goal of this project was to evaluate the effectiveness of Coriandrum sativum (Cilantro) as a potential lead (II), Pb²⁺, phytoremediator. C. sativumplants were allowed to grow for 43 days while exposed to with different amounts of lead nitrate, Pb(NO₃)₂. Lead exposure was accomplished by regular watering with a concentration series of lead nitrate solutions. The roots and shoots of these plants were separated and dried. Ground plant material was liquefied by nitric acid digestion. The amount of lead absorbed …

Streptococcus Agalactiae Strains With Chromosomal Deletions Evade Detection With Molecular Methods, Isabella A. Tickler, Fred C. Tenover, Scott Dewell, Victoria M. Le, Rachel N. Blackman, Richard V. Goering, Amy E. Rogers, Heather Piwonka, Brittney D. Jung-Hynes, Derrick J. Chen, Michael J. Loeffelholz, Devasena Gnanashanmugam, Ellen Jo Baron

Biology Faculty Publications

Surveillance of circulating microbial populations is critical for monitoring the performance of a molecular diagnostic test. In this study, we characterized 31 isolates of Streptococcus agalactiae (group B Streptococcus [GBS]) from several geographic locations in the United States and Ireland that contain deletions in or adjacent to the region of the chromosome that encodes the hemolysin gene cfb, the region targeted by the Xpert GBS and GBS LB assays. PCR-negative, culture-positive isolates were recognized during verification studies of the Xpert GBS assay in 12 laboratories between 2012 and 2018. Whole-genome sequencing of 15 GBS isolates from 11 laboratories revealed …

Spinal Matrix Metalloproteinase 8 Regulates Painafter Peripheral Trauma, Maral Tajerian, J. David Clark

Publications and Research

It is well documented that pain chronification requires a host of plastic mechanisms at the spinal cord (SC) level, including alterations in neuronal and glial structure and function. Such cellular plasticity necessitates the existence of a plastic extracellular matrix(ECM). Here, we describe a key role for ECM remodeling in the regulation of chronic pain following peripheral injury. Three weeks following tibia fracture in mice, we show increased levels of MMP8 in the SC. Furthermore, we show that the pharmacological or genetic down regulation of MMP8 ameliorates the pain phenotype observed after injury. These results delineate an extracellular mechanism for pain …

Cell Differentiation And Proliferation During Brain Development, Sarah Maxson

Undergraduate Honors Thesis Projects

During brain development, cells can proliferate and differentiate into either neuronal or glial cells. Neuronal cells are capable of sending signals, while glial cells function to provide nutrients and structural support. The ratio of these cell types can give insight into brain function in comparative studies among species and in studies of phylogenesis and pathology. In order to complete this project in neuroscience, a new technique called the isotropic fractionator was utilized to estimate a neuronal vs. non-neuronal cell count of the rodent brain. Brains ranging from age postnatal day 1 to postnatal day 23 were dissected into 4 regions …

Functional And Transcriptomic Characterization Of Carboplatin-Resistant A2780 Ovarian Cancer Cell Line, Tamara Viscarra, Kurt Buchegger, Ignacio Jofre, Ismael Riquelme, Louise Zanella, Michel Abanto, Alyssa C. Parker, Stephen R. Piccolo, Juan Carlos Roa, Carmen Ili, Priscilla Brebi

Faculty Publications

Background

Ovarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780.

Methods

The cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 μM for 2 h. Once 20 cycles of exposure to …

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards …

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential …

Diversity Of Resistance Mechanisms In Carbapenem-Resistant Enterobacteriaceae At A Health Care System In Northern California, From 2013 To 2016, Fiona Senchyna, Rajiv L. Gaur, Johanna Sandlund, Cynthia Truong, Guillaume Tremintin, Dietmar Kültz, Carlos A. Gomez, Fiona B. Tamburini, Tessa Andermann, Ami Bhatt, Isabella A. Tickler, Nancy Watz, Indre Budvytiene, Gongyi Shi, Fred C. Tenover, Niaz Banaei

Biology Faculty Publications

The mechanism of resistance in carbapenem-resistant Enterobacteriaceae (CRE) has therapeutic implications. We comprehensively characterized emerging mechanisms of resistance in CRE between 2013 and 2016 at a health system in Northern California. A total of 38.7% (24/62) of CRE isolates were carbapenemase gene-positive, comprising 25.0% (6/24) blaOXA-48 like, 20.8% (5/24) bla_KPC, 20.8% (5/24) bla_NDM, 20.8% (5/24) bla_SME, 8.3% (2/24) bla_IMP, and 4.2% (1/24) bla_VIM. Between carbapenemases and porin loss, the resistance mechanism was identified in 95.2% (59/62) of CRE isolates. Isolates expressing bla_KPC were 100% susceptible to ceftazidime–avibactam, meropenem–vaborbactam, …

A Cross-Species Analysis Reveals A General Role For Piezo2 In Mechanosensory Specialization Of Trigeminal Ganglia From Tactile Specialist Birds, Eve R. Schneider, Evan O. Anderson, Viktor V. Feketa, Marco Mastrotto, Yury A. Nikolaev, Elena O. Gracheva, Sviatoslav N. Bagriantsev

Biology Faculty Publications

A major challenge in biology is to link cellular and molecular variations with behavioral phenotypes. Here, we studied somatosensory neurons from a panel of bird species from the family Anatidae, known for their tactile-based foraging behavior. We found that tactile specialists exhibit a proportional expansion of neuronal mechanoreceptors in trigeminal ganglia. The expansion of mechanoreceptors occurs via neurons with intermediately and slowly inactivating mechanocurrent. Such neurons contain the mechanically gated Piezo2 ion channel whose expression positively correlates with the expression of factors responsible for the development and function of mechanoreceptors. Conversely, Piezo2 expression negatively correlates with expression of molecules mediating …

Interaction And Regulation Between Lipid Mediator Phosphatidic Acid And Circadian Clock Regulators, Sang-Chul Kim, Sang-Chul Kim, Dmitri Nusinow, Maria Sorkin, Maria Sorkin, Jose Pruneda-Paz, Xuemin Wang, Xuemin Wang

Biology Department Faculty Works

Circadian clocks play important roles in regulating cellular metabolism, but the reciprocal effect that metabolism has on the clock is largely unknown in plants. Here we show that the central glycerolipid metabolite and lipid mediator phosphatidic acid (PA) interacts with and modulates the function of the core clock regulators LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED1 (CCA1) in Arabidopsis thaliana. PA reduced the ability of LHY and CCA1 to bind the promoter of their target gene TIMING OF CAB EXPRESSION1. Increased PA accumulation and inhibition of PA-producing enzymes had opposite effects on circadian clock outputs. Diurnal change in levels …

Identification And Characterization Of Barrier Insulator Activity In The T-Cell Receptor Alpha Locus Control Region, Gayathri Devi Raghupathy

Dissertations, Theses, and Capstone Projects

Genes of different spatiotemporal expression profiles are often juxtaposed in the genome. This organization raises risks of cross-regulatory influences from neighboring genes; for instance heterochromatin can spread over euchromatin or long-range acting enhancers can inappropriately activate genes. Gene regulatory elements such as Locus Control Regions (LCR) and Insulators prevent such cross-communications and allow for normal gene expression patterns. In transgenic systems, LCRs limit influences from surrounding chromatin by providing site-of-integration independent and specific spatiotemporal expression upon a linked transgene. The field’s understanding of the ability of an LCR to overcome chromatin influences and allow site-of-integration independent expression is minimal. Interestingly, …

Molecular Analysis Of Cone Photoreceptor Genesis From A Specific Retinal Progenitor Population, Diego F. Buenaventura

Dissertations, Theses, and Capstone Projects

There are two types of photosensitive cells of the retina that contribute to image formation: Cone photoreceptors that mediate color discrimination and rods that provide photosensitivity in low-light conditions. Given the importance of cones in high acuity and color vision, deficiencies in this cell type that result from ailments such as retinitis pigmentosa and macular degeneration can lead to a debilitating loss of vision. Currently, one of the most pressing goals in the field of retinal development is the elucidation of the gene regulatory networks (GRN) involved in inducing an undifferentiated cell into becoming a functional cone photoreceptor.

Recently, an …

Putative Cellular And Molecular Roles Of Zika Virus In Fetal And Pediatric Neuropathologies, Rajendra Ghardbaran, Rajendra Ghardbaran, Latchman Somenarain

Publications and Research

Although the World Health Organization declared an end to the recent Zika virus (ZIKV) outbreak and its association with adverse fetal and pediatric outcome, on November 18, 2016, the virus still remains a severe public health threat. Laboratory experiments thus far supported the suspicions that ZIKV is a teratogenic agent. Evidence indicated that ZIKV infection cripples the host cells' innate immune responses, allowing productive replication and potential dissemination of the virus. In addition, studies suggest potential transplacental passage of the virus and subsequent selective targeting of neural progenitor cells (NPCs). Depletion of NPCs by ZIKV is associated with restricted brain …

Microrna-4719 And Microrna-6756-5p Correlate With Castration-Resistant Prostate Cancer Progression Through Interleukin-24 Regulation, Dibash K. Das, Leah Persaud, Moira Sauane

Publications and Research

Prostate cancer (PCa) is the second leading cause of cancer death in the United States. The five-year survival rate for men diagnosed with localized PCa is nearly 100%, yet for those diagnosed with aggressive PCa, it is less than 30%. The pleiotropic cytokine Interleukin-24 (IL-24) has been shown to specifically kill PCa cells compared to normal cells when overexpressed in both in vitro and in vivo studies. Despite this, the mechanisms regulating IL-24 in PCa are not well understood. Since specific microRNAs (miRNAs) are dysregulated in PCa, we used miRNA target prediction algorithm tools to identify miR-4719 and miR-6556-5p as …

Exploring The Ipf Lung Through The Lens Of Single Cell Rna Sequencing, Taylor Adams, Jonas Schupp

Yale Day of Data

This poster illustrates the differences between the IPF disease-specific variety of lung macrophages and the two varieties of macrophages known to reside in the normal human lung.