Cell and Developmental Biology Commons^™

Understanding The Pathogenesis Of Renal Medullary Carcinoma, Melinda Soeung

Dissertations and Theses (Open Access)

Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the …

Regulation Of Lung Mesenchymal Cells By Epithelial Wnt Ligands, Odemaris Narvaez Del Pilar

Dissertations and Theses (Open Access)

The mesenchyme comprises of heterogeneous cell populations that support neighboring structures and are integral to intercellular signaling. Despite such importance, mesenchymal cells are poorly defined morphologically and molecularly. Their signaling regulation is not well understood, lagging their counterparts in the epithelial, endothelial, and immune lineages. Leveraging single-cell RNA-seq, three-dimensional imaging, and lineage tracing, first, we delineated different lung mesenchymal cell types and classified them into three-proximal-distal axes in the neonatal and adult murine lung. Each axis is associated to the structure they support – the endothelium, epithelium and interstitium. We also identified two subpopulations of neonatal lung myofibroblasts – ductal …

The Effect Of Sub 5% Oxygen Tension On In Vitro Human Embryo Development, Bradley James Link

EVMS School of Health Professions Theses & Dissertations

Objective: To determine the impact of < 5% O₂ tension on the in vitro development of human pre-implantation embryos. It was hypothesized that the optimal O₂ tension would differ from the commonly utilized 5%, as shown by beneficial effects after the implementation of a more physiological O₂ tension such as 2% for either the partial or full duration of in vitro culture.

Aim: To conduct a randomized controlled study to determine the effect of O₂ tension during in vitro human embryo culture on the production of reactive oxygen species (ROS), apoptosis, gene expression and embryo development.

Background: The …

Bone Morphogenetic Protein Signaling Requirement In Centripetal Migration In Drosophila Melanogaster Oogenesis, Sheila Mosallaei

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cells interact with each other via signals to coordinate migration for proper tissue development and maintenance, immunity and tissue repair. Signals regulate migration via changes to cytoskeletal components or transcriptional regulation. Here, I used Drosophila melanogaster to investigate whether and how a transcriptional signal, Bone Morphogenetic Protein signaling, drives a cell migration, centripetal migration. The migrating cells, centripetal follicle cells, consist of two subsets of cells, “leading” and “following” centripetal follicle cells, that although adjacent to each other, migrate differently. The differences in modes of migration correlate to differential gene expression in the centripetal follicle cells. The leading centripetal follicle …

Collagen Xi Impact On Structure And Function Of The Vertebrate Inner Ear In A Zebrafish Model, Makenna Hardy

Boise State University Theses and Dissertations

The ear is essential to maintaining balance and hearing; both of which can be linked to one another and significantly impact a person’s quality of life. Although aging and damage are more common reasons for hearing loss, congenital ear defects still have a considerable impact on our population. The function of the ear can be affected by structural deformities to the ear and its components which results in hearing loss. Mutations and single nucleotide polymorphisms in the gene encoding Collagen XI alpha one chain (COL11A1) protein can play a role in hearing and balance dysfunction in humans as seen in …

Suppression Of Dc-Sign And Gh Reveals Complex, Subset-Specific Mechanisms For Kshv Entry In Primary B Lymphocytes, Nancy Palmerin, Farizeh Aalam, Romina Nabiee, Murali Muniraju, Javier Gordon Ogembo, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of multiple cancers in immunocompromised patients including two lymphoproliferative disorders associated with KSHV infection of B lymphocytes. Despite many years of research into the pathogenesis of KSHV associated diseases, basic questions related to KSHV molecular virology remain unresolved. One such unresolved question is the cellular receptors and viral glycoproteins needed for KSHV entry into primary B lymphocytes. In this study, we assess the contributions of KSHV glycoprotein H (gH) and the cellular receptor DC-SIGN to KSHV infection in tonsil-derived B lymphocytes. Our results show that (1) neither KSHV-gH nor DC-SIGN are essential …

African Swine Fever Virus Cd2v Protein Induces Β-Interferon Expression And Apoptosis In Swine Peripheral Blood Mononuclear Cells, Sabal Chaulangain, Gustavo A. Delhon, Sushil Khatiwada, Daniel L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

African swine fever (ASF) is a hemorrhagic disease of swine characterized by massive lymphocyte depletion in lymphoid tissues due to the apoptosis of B and T cells, a process likely triggered by factors released or secreted by infected macrophages. ASFV CD2v (EP402R) has been implicated in viral virulence and immunomodulation in vitro; however, its actual function(s) remains unknown. We found that CD2v expression in swine PK15 cells induces NF-κB-dependent IFN-β and ISGs transcription and an antiviral state. Similar results were observed for CD2v protein treated swine PBMCs and macrophages, the major ASFV target cell. Notably, treatment of swine PBMCs and …

Bcr Affinity Influences T-B Interactions And B Cell Development In Secondary Lymphoid Organs, Alec J. Wishnie, Tzippora Chwat-Edelstein, Mary Attaway, Bao Q. Vuong

Publications and Research

B cells produce high-affinity immunoglobulins (Igs), or antibodies, to eliminate foreign pathogens. Mature, naïve B cells expressing an antigen-specific cell surface Ig, or B cell receptor (BCR), are directed toward either an extrafollicular (EF) or germinal center (GC) response upon antigen binding. B cell interactions with CD4+ pre-T follicular helper (pre- Tfh) cells at the T-B border and effector Tfh cells in the B cell follicle and GC control B cell development in response to antigen. Here, we review recent studies demonstrating the role of B cell receptor (BCR) affinity in modulating T-B interactions and the subsequent differentiation of B …

Dimeric Allostery Mechanism Of The Plant Circadian Clock Photoreceptor Zeitlupe, Francesco Trozzi, Feng Wang, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

In Arabidopsis thaliana, the Light-Oxygen-Voltage (LOV) domain containing protein ZEITLUPE (ZTL) integrates light quality, intensity, and duration into regulation of the circadian clock. Recent structural and biochemical studies of ZTL indicate that the protein diverges from other members of the LOV superfamily in its allosteric mechanism, and that the divergent allosteric mechanism hinges upon conservation of two signaling residues G46 and V48 that alter dynamic motions of a Gln residue implicated in signal transduction in all LOV proteins. Here, we delineate the allosteric mechanism of ZTL via an integrated computational approach that employs atomistic simulations of wild type and …

Analysis Of The Role Of Akirin Interactions With Nuclear Body Proteins During Myogenesis, Laura Yorke

Master of Science in Integrative Biology Theses

Akirin is a highly conserved, small nuclear protein of indeterminate structure ubiquitously expressed in non-fungal eukaryotic species. It was first discovered in the innate immune response, but many other functions have since been found, including embryonic muscle patterning and myogenesis. Animals with either nonfunctional or missing Akirin have aberrations in embryonic muscle patterning, along with other defects. Akirin interacts with transcription factors such as Twist to coordinate development through interfacing between Twist and other complexes, such as the Brahma Chromatin Remodeling Complex (BRM). Therefore, Akirin likely plays a general role in transcription during early development, interfacing with other transcriptional machinery …

Exploring The Relationship Between Cellular Senescence, Apolipoprotein E, And Alzheimer’S Disease, Buay Deng

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Alzheimer’s disease (AD) is the most common form of dementia in the world and currently affects more than 50 million people and has no cure to date. One of its major neuropathological hallmarks is the presence of senile plaques—formed from Amyloid-β (Aβ) oligomers. Aβ has also been associated with the development of cellular senescence in preclinical AD models, suggesting that cellular senescence may be mechanistically involved in disease progression. Cellular senescence is a stress response that occurs when cells are exposed to degenerative factors that puts them into permanent cell cycle arrest, this process increases with age. Apolipoprotein E (ApoE) …

Notch Signaling Represses Cone Photoreceptor Formation Through The Regulation Of Retinal Progenitor Cell States, Xueqing Chen, Mark M. Emerson

Publications and Research

Notch signaling is required to repress the formation of vertebrate cone photoreceptors and to maintain the proliferative potential of multipotent retinal progenitor cells. However, the mechanism by which Notch signaling controls these processes is unknown. Recently, restricted retinal progenitor cells with limited proliferation capacity and that preferentially generate cone photoreceptors have been identified. Thus, there are several potential steps during cone genesis that Notch signaling could act. Here we use cell type specific cis-regulatory elements to localize the primary role of Notch signaling in cone genesis to the formation of restricted retinal progenitor cells from multipotent retinal progenitor cells. Localized …

Human Oncoprotein 5mp Suppresses General And Repeat-Associated Non-Aug Translation Via Eif3 By A Common Mechanism, Chingakham Ranjit Singh, M. Rebecca Glineburg, Chelsea Moore, Naoki Tani, Rahul Jaiswal, Ye Zou, Eric Aube, Sarah Gillaspie, Mackenzie Thornton, Ariana Cecil, Madelyn Hilgers, Azuma Takasu, Izumi Asano, Masayo Asano, Carlos R. Escalante, Akira Nakamura, Peter K. Todd, Katsura Asano

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

eIF5-mimic protein (5MP) is a translational regulatory protein that binds the small ribosomal subunit and modulates its activity. 5MP is proposed to reprogram non-AUG translation rates for oncogenes in cancer, but its role in controlling non-AUG initiated synthesis of deleterious repeat-peptide products, such as FMRpolyG observed in fragile-X-associated tremor ataxia syndrome (FXTAS), is unknown. Here, we show that 5MP can suppress both general and repeat-associated non-AUG (RAN) translation by a common mechanism in a manner dependent on its interaction with eIF3. Essentially, 5MP displaces eIF5 through the eIF3c subunit within the preinitiation complex (PIC), thereby increasing the accuracy of initiation. …

Novel Scalable And Simplified System To Generate Microglia-Containing Cerebral Organoids From Human Induced Pluripotent Stem Cells, Brittany Bodnar, Yongang Zhang, Jinbiao Liu, Yuan Lin, Peng Wang, Zhengyu Wei, Sami Saribas, Yuanjun Zhu, Fang Li, Xu Wang, Wenli Yang, Qingsheng Li, Wen-Zhe Ho, Wenhui Hu

Nebraska Center for Virology: Faculty Publications

Human cerebral organoid (CO) is a three-dimensional (3D) cell culture system that recapitulates the developing human brain. While CO has proved an invaluable tool for studying neurological disorders in a more clinically relevant matter, there have still been several shortcomings including CO variability and reproducibility as well as lack of or underrepresentation of certain cell types typically found in the brain. As the technology to generate COs has continued to improve, more efficient and streamlined protocols have addressed some of these issues. Here we present a novel scalable and simplified system to generate microglia-containing CO (MCO). We characterize the cell …

Cellular Toxicity Of Malonato (Ethylenediamine) Platinum (Ii) In Models Of Cancer, Sidikat Olanrewaju Olajuwon

Masters Theses & Specialist Projects

Platinum(II) compounds including the three FDA approved drugs, cisplatin, carboplatin, and oxaliplatin, are composed of two structural components, a leaving ligand, and a non-leaving ligand, each attached to a central platinum(II) atom. All bifunctional platinum compounds studied have similar mechanisms of initiating cell death. However, their efficacy as chemotherapeutics depends on the tissues in which the cancer originates. No model has explained these tissue-specific efficacies. We hypothesized that the efficacies of these platinum compounds vary due to structural differences in the leaving ligands. To test the influence of the leaving ligand on cellular survival, novel platinum compounds were synthesized, and …

College Of Natural Sciences Newsletter, July 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 2, Issue 7.

Page 1 Dean's Message
Page 2 Celebrating Three Years
Page 3 Summer School Travel
Page 4 Media Coverage of CNS
Page 5 Chemistry Teachers Visit
Page 5 Remembering Dr. Warren Hein
Page 6 Research Spotlights: Undergraduate Summer Experiences
Page 7 Open PRAIRIE Data; Grants Awarded in CNS

Directed Genome Evolution To Identify Genes For Macrophage Survival By Staphylococcus Agnetis, Sonali Lakshika Anne Lenaduwe Lokuge

Graduate Theses and Dissertations

Bacterial Chondronecrosis with Osteomyelitis (BCO) is a debilitating infection that negatively impacts animal welfare and costs the broiler industry billions of dollars annually. We have previously isolated Staphylococcus agnetis 908 from BCO samples obtained from broilers at the University of Arkansas research farm. This isolate can induce BCO lameness at greater than 50% in broilers exposed to the pathogen in drinking water. We found that S. agnetis 908 is capable of surviving and escaping macrophages compared to a closely related cattle isolate,1379. Through Directed Genome Evolution (DGE) we identified that this difference is at least partially associated with an alanine …

Host-Parasite Interactions Within Food Webs, Adam Zvanut Hasik

Graduate Theses and Dissertations

Parasitism is one of the most common life history strategies employed in nature, yet the effects of parasites are often thought to be minimal, and the vast majority of studies fail to consider parasites and their effects on host organisms. This is likely a problem, as the magnitude of parasite-mediated effects on their hosts can be quite large. Additionally, the effects of parasites are known to extend beyond the host to affect other species interactions. I used a series of approaches to gain a more integral understanding of host-parasite interactions by studying (1) the effects of parasites on biotic interactions …

Divergent Regulatory Roles Of Nurd Chromatin Remodeling Complex Subunits Gatad2 And Chd4 In Caenorhabditis Elegans, Nicole Lynn Golden

Theses and Dissertations

During stress, a protective cellular network known as the heat shock response (HSR) is induced to maintain protein-folding homeostasis, or proteostasis. While the HSR is essential for stress resistance, its misregulation is associated with neurodegenerative disease and cancer. Using the nematode model organism Caenorhabditis elegans, we have identified the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylase) as a novel regulator of the HSR. Here, we begin with a brief introduction of the HSR and chromatin remodeling complexes in C. elegans, prior to presenting our findings in a series of two chapters. In chapter one, we outline a set of …

Distinct Spatiotemporal Regulation Of The Cytoprotective Heat Shock Response In Caenorhabditis Elegans, Rosemary Nadine Plagens

Theses and Dissertations

Every organism studied to-date utilizes the heat shock response (HSR) to maintain protein-folding homeostasis (proteostasis) during temperature or other protein-folding stress. The HSR has been well characterized using acute heat stress (HS) in single-celled models, but less is known about how distinct cell types and tissues respond to HS. Furthermore, how metazoans respond to prolonged HS at the molecular level remains relatively unexplored. The model organism C. elegans, with its genetic tractability and distinct tissues and behaviors, has been used extensively in the field to characterize the acute HSR, but with considerable variability across labs regarding HS temperature and duration. …

Evaluating Effect Of Folic Acid On Mouse Embryonic Fibroblast Cells With Impaired Dna Repair System, Suneeti Madhavan

Master's Theses

Mandatory folic acid (FA) fortification programs have been introduced in many countries since 1998 [1]. This fortification program, especially when combined with vitamin supplements taken for health purposes, can lead to higher-than-normal levels of synthetic FA in the body [2]. Recent research has linked high levels of synthetic FA (more than the daily requirement of 400μg/day) with increased incidences of cancer [2-7]. In comparison, low levels of FA have been shown to cause DNA damage due to impaired DNA repair processes [8,9]. This study hypothesizes that increased levels of FA give rise to DNA modification. Therefore, if cells harbor an …

Characterization Of Iron-Sulfur Cluster Biogenesis In Methanogenic Archaea, Thomas Modlin Deere

Graduate Theses and Dissertations

Iron-sulfur (Fe-S) clusters are among the oldest cofactors on the planet, used by proteins in almost all forms of life on Earth to carry out processes ranging from energy transfer to DNA replication. Among the organisms believed to use these Fe-S proteins more extensively than almost any others are the methanogens, an ancient lineage of archaeal microbes that produce methane as a required product of their metabolism. Methane, the primary component of commercial natural gas, is both a potent greenhouse gas and an important fossil fuel. It can also be renewably produced as a biofuel. Biogenic methane is almost entirely …

The Characterization Of Angiopoietin-Like Protein 4 Overexpression In Triple Negative Breast Cancer, Jodi Simeon

Graduate Theses and Dissertations

Triple Negative Breast Cancer (TNBC) is highly invasive and metastatic with approximately 15% of patients developing liver metastases. The primary treatment of metastatic TNBC is chemotherapy, however, there is an increased chance of resistance to this therapeutic technique. If Breast Cancer Liver Metastasis (BCLM) is left untreated most patients survive only 4 to 8 months with a very rare 5-year survival. Therefore, it is imperative to analyze markers and molecular pathways that TNBC cells use to progress, invade, and metastasize to the liver. The aim of this study was to examine the overexpression of angiopoietin-like 4 (ANGPTL4) in TNBC cells …

Evaluating Bioenergetics And Mitochondrial Dynamics In Patient Fibroblasts With Pathogenic Mitochondrial Dna Mutations Causing Leigh Syndrome, Ajibola Bakare

Graduate Theses and Dissertations

Leigh syndrome (LS) is a rare fatal mitochondrial disorder of infants caused by pathogenic mutations in the nuclear (nDNA) or mitochondrial DNA (mtDNA) leading to mitochondrial dysfunction. The extent to which pathogenic mtDNA variants regulate disease severity in LS is not well understood. The heterogeneous nature of this disorder, based in part by complex mitochondrial genetics, and the nuclear and mitochondrial cross-talk has made it particularly challenging to investigate and develop therapies for treating LS . While the prognosis is poor, several studies are underway to understand the pathophysiology of LS. This dissertation provides a comprehensive structural and functional analysis …

A Time-Course Characterization Of Muscle Function And Mitochondrial Markers During Colorectal Cancer-Induced Cachexia In Tumor-Bearing Male Mice, Ana Cabrera Ayuso

Graduate Theses and Dissertations

Cachexia is a multisystemic and multifactorial syndrome prevalent in cancer patients. It is clinically defined by involuntary loss of >5% weight in a six-month window, despite nutritional interventions. A negative energy balance characterizes cancer cachexia (CC), it is associated with weakness and fatigue in skeletal muscle. Impaired muscle function is associated with lower quality of life in cancer patients. Defects in mitochondrial function are strongly associated with muscle wasting. This study explored muscular contractile function and mitochondrial quality control (MQC) markers in soleus, gastrocnemius, and tibialis anterior (TA) muscles of C26-induced male tumor-bearing mice during a 25-day time course. It …

Experimental And Analysis Of Electromagnetic Characterization Of Biological And Non-Biological Materials In Microwave, Millimeter-Wave, And Terahertz Frequency Bands, Nagma Vohra

Graduate Theses and Dissertations

The goal of this research is to characterize the electromagnetic properties of biological and non-biological materials at terahertz (THz), millimeter-wave, and microwave frequency bands. The biological specimens are measured using the THz imaging and spectroscopy system, whereas the non-biological materials are measured using the microwave and millimeter-wave free-space system. These facilities are located in the Engineering Research Center at the University of Arkansas. The THz imaging system (TPS 3000) uses a Ti-Sapphire laser directed on the photoconductive antennas to generate a THz time domain pulse. Upon using the Fourier Transform, the spectrum of the pulsed THz signal includes frequencies from …

Efficacy Of Conditional And Constitutive Crispr/Cas9 In Rice Genome, Zahra Alizada

Graduate Theses and Dissertations

Constitutive expression of Cas9 leads to a higher editing efficiency; however, it also increases the chances of off-target mutations. Thus, transient expression of Cas9 is a desirable approach to achieve higher targeting efficiency and to curb the off-target effects. It was previously shown that heat-inducible expression of Cas9 had an editing efficiency of 45% as compared to the strong constitutive expression, and the heat-shock induced mutations were inherited by the next generation. In this study, cold-inducible promoter, AtRD29a, was used for driving Cas9 expression, and evaluated for its editing efficiency upon cold-treatment on the GUS transgene loci. The expression analysis …

Recoding Of Stop Codons Expands The Metabolic Potential Of Two Novel Asgardarchaeota Lineages, Jiarui Sun, Paul N. Evans, Emma J. Gagen, Ben J. Woodcroft, Brain P. Hedlund, Tanja Woyke, Philip Hugenholtz, Christian Rinke

Life Sciences Faculty Research

Asgardarchaeota have been proposed as the closest living relatives to eukaryotes, and a total of 72 metagenome-assembled genomes (MAGs) representing six primary lineages in this archaeal phylum have thus far been described. These organisms are predicted to be fermentative heterotrophs contributing to carbon cycling in sediment ecosystems. Here, we double the genomic catalogue of Asgardarchaeota by obtaining 71 MAGs from a range of habitats around the globe, including the deep subsurface, brackish shallow lakes, and geothermal spring sediments. Phylogenomic inferences followed by taxonomic rank normalisation confirmed previously established Asgardarchaeota classes and revealed four additional lineages, two of which were consistently …

The Neurological Asymmetry Of Self-Face Recognition, Aleksandra Janowska, Brianna Balugas, Matthew Pardillo, Victoria Mistretta, Katherine Chavarria, Janet Brenya, Taylor Shelansky, Vanessa Martinez, Kitty Pagano, Nathira Ahmad, Samantha Zorns, Abigail Straus, Sarah Sierra, Julian Keenan

Department of Biology Faculty Scholarship and Creative Works

While the desire to uncover the neural correlates of consciousness has taken numerous directions, self-face recognition has been a constant in attempts to isolate aspects of self-awareness. The neuroimaging revolution of the 1990s brought about systematic attempts to isolate the underlying neural basis of self-face recognition. These studies, including some of the first fMRI (functional magnetic resonance imaging) examinations, revealed a right-hemisphere bias for self-face recognition in a diverse set of regions including the insula, the dorsal frontal lobe, the temporal parietal junction, and the medial temporal cortex. In this systematic review, we provide confirmation of these data (which are …

A Global Metagenomic Map Of Urban Microbiomes And Antimicrobial Resistance, David Danko, Daniela Bezdan, Evan E. Afshin, Sofia Ahsanuddin, Chandrima Bhattacharya, Daniel J. Butler, Kern Rei Chng, Daisy Donnellan, Jochen Hecht, Katelyn Jackson, Katerina Kuchin, Mikhail Karasikov, Abigail Lyons, Lauren Mak, Dmitry Meleshko, Harun Mustafa, Beth Mutai, Russell Y. Neches, Amanda Ng, Olga Nikolayeva, Tatyana Nikolayeva, Eileen Png, Krista A. Ryon, Jorge L. Sanchez, Heba Shaaban, Maria A. Sierra, Dominique Thomas, Ben Young, Omar O. Abudayyeh, Josue Alicea, Malay Bhattacharyya, Ran Blekhman, Eduardo Castro-Nallar

ISI Best Publications

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and …