Biotechnology Commons^™

Deciphering The Contribution Of Microglia To Neurodegeneration In Friedreich's Ataxia, Sydney N. Gillette

Master's Theses

Friedreich's ataxia (FRDA) is the most prevalent inherited ataxia, affecting one in every 50,000 individuals in the United States. This hereditary condition is caused by an abnormal GAA trinucleotide repeat expansion within the first intron of the frataxin gene resulting in decreased levels of the frataxin protein (FXN). Insufficient cellular frataxin levels results in iron accumulation, increased reactive oxygen species production and mitochondrial dysfunction. Tissues most heavily impacted are those most dependent on oxidative phosphorylation as an energy source and include the nervous system and muscle tissue. This is evident in the clinical phenotype which includes muscle weakness, ataxia, neurodegeneration …

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Uncovering Novel Small Regulatory Rna In Protostome, Sweta Khanal

Dissertations

Small RNAs play pivotal roles in post-transcriptional gene regulation across diverse phylum of protostomes. In this study, we investigate the functional significance of atypical miRNAs, mirtron miR-1017 in Drosophila. Through ectopic expression in neuronal cells, we demonstrate that miR-1017 extends lifespan by targeting its host transcript, acetylcholine receptor Dα2, and influencing its splicing. This novel trans-regulatory function suggests a mechanism for mirtron evolution, highlighting the interplay between splicing and post-transcriptional regulation. Additionally, we profile small RNA populations in the polychaete developmental model Capitella teleta, shedding light on the small RNA landscape in annelid worms. Our analysis reveals a rich …

Qualitative Assessment Of Human Embryonic- And Induced Pluripotent Stem Cell Derived Neural Stem Cells Under Cgmp Methods, Michelle Hernandez

Electronic Theses, Projects, and Dissertations

Neural stem cell therapies represent a promising tool for the development of regenerative medicine and are being tested in clinical trials for several neurological disorders. However, the clinical applicability of stem cell therapies is dependent on the implementation of current good manufacturing practices (cGMPs) to ensure the quality, safety, and consistency that stem cell products need to meet FDA regulatory requirements. As such, there is a need for a shift to xeno-free methodologies so experimental conditions are cGMP compliant. The purpose of this study is to test a GMP compatible production method to generate multipotent neural stem cells (NSCs) from …

Investigating Vital Neutrophil Extracellular Trap Pathogen Response In Neutropenic Individuals, Ryan Illig

Thinking Matters Symposium

Neutrophils, also called polymorphonuclear leukocytes (PMNs), constitute the majority of innate immune cells. These cells possess a complex arsenal of functions that allow them to detect and eliminate a broad spectrum of pathogens. Neutropenia is characterized by decreased levels of neutrophils in the bloodstream, typically falling below the normal range. Moderate to severe neutropenia can increase the risk of pathogenic infections and without treatment can be life-threatening. Although the concentration of neutrophils in neutropenic individuals is decreased, upon activation, neutrophils still release neutrophil extracellular traps (NETs). NETs are pivotal in combating a spectrum of pathogens through their non-selective nature. Overreactive …

Annotation Of Hypothetical Genes In Lactococcus Lactis Ssp. Il403, Jennifer A. Tangires

Student Scholar Showcase

The human gastrointestinal tract (GIT) harnesses various microbial organisms involved in almost all processes of physiological homeostasis, among these are lactic acid bacteria (LAB). These bacteria, almost all of which belong to the order Lactobacillales, are able to produce lactic acid, and play an important role in food preservation because they produce bacteriocins. Bacteriocins are antimicrobial proteins that are used to fight off related bacteria in their environment that are competing for the same resources. This study focuses on a specific LAB strain, Lactococcus lactis ssp. IL1403 where 21.9% of its predicted genes have not yet been assigned a function. …

The Impact Of Mutations In The Arabidopsis Apetela (Ap3) Gene, Hazel R. Frans, Tara Phelps-Durr

SACAD: Scholarly Activities

The purpose of this research is to understand the molecular functioning of the Arabidopsis thaliana Apetela (Ap3) gene. We created mutations in two sites of the gene, AP3-3 and AP3-5. These are predicted to change AP3 protein structure, which may result in a mutated flower. Analyzing the effects of new mutations allows an understanding of protein formation both in plants and humans.

In Silico Analysis Of C-Type Lectins As Co-Infection Receptors Of Dengue And Chikungunya Viruses In Aedes Aegypti, Munawir Sazali, R. C. Hidayat Soesilohadi, Nastiti Wijayanti, Tri Wibawa, Arif Nur Muhammad Ansori

Makara Journal of Science

Aedes aegypti is a primer vector of dengue virus (DENV) and chikungunya virus (CHIKV). The susceptibility of mosquitoes to DENV and CHIKV depends on their recognition receptor of pathogens. C-type lectins (CTLs) are an important mediator of virus infection in A. aegypti. This study aims to identify potential receptors and determine the binding affinity between ligand–receptor interaction, CTLs and virus envelopes (DENV-1, 2, 3, and 4 and CHIKV) interaction based on in silico analysis. Sample sequences were obtained from GenBank (NCBI), and 10 CTLs were acquired from VectorBase. Homology modeling based on a minimum standard of 20% was processed …

Panorama Of Human Embryo-Derived Cells In Biomedicine And Progress In Their Research And Regulation, Jianchao Gao, Yaojin Peng, Wei Wei, Shuang Lu, Chenyan Gao

Bulletin of Chinese Academy of Sciences (Chinese Version)

Since the establishment of the first human diploid cell line derived from aborted fetal tissue in the 1960s, human embryoderived cells have been widely used in biomedical field and significantly contributes to improving human health. In recent years, human pluripotent stem cells, including human embryonic stem cells (hESCs), have shown great therapeutic potential in regenerative medicine, and thus received great attention from governments and the public. However, due to various factors such as history, culture, religious beliefs, ethics and morality, research and application involving human embryo-derived cells have been controversial worldwide. This study explores the history and progress of human …

Mechanistic And Engineering Studies Of Lov Photoreceptors In Yeast, Matthew M. Cleere

Dissertations, Theses, and Capstone Projects

A variety of cellular biosensors have evolved which can translate electromagnetic radiation from the environment into biological functions. Light-Oxygen-Voltage (LOV) domains in particular, are a group of photoreceptors that respond to blue wavelengths of light and can become a cellular photoswitch by converting this stimulus through their attached effector domains. For instance, the Helix-Turn-Helix (HTH) DNA-binding activity of the bacterial transcription factor EL222 and the Regulator of G-protein Signaling (RGS) in the fungal membrane associating protein BcLOV4 are both induced by blue-light sensing LOV domains. While previous work has provided the field with a structural characterization of LOV proteins in …

Temporal Distribution Of Potential Waterborne Pathogens In Sequiota Spring, William J. Durstock

Graduate Theses/Dissertations

Waterborne pathogens from human fecal matter pose a significant health risk in karst environments, where domestic wastewater can easily be transferred to the shallow groundwater system via old, leaky septic tanks and damaged sewer lines. This study monitored fecal indicator bacteria (FIB) and potential pathogens in Sequiota Spring located in the karst region of southwest Missouri, using Microbial Source Tracking (MST) and Illumina DNA sequencing of bacterial 16S rRNA genes. MST identified high levels of human fecal indicator bacteria (HFIB) (up to 110,000 cells/L) in July 2020. By June 2022, HFIB levels had dropped significantly (55-fold reduction) after the City …

Cyp6g2 Is The Major P450 Epoxidase Responsible For Juvenile Hormone Biosynthesis In Drosophila Melanogaster, Qiangqiang Jia, Liu Yang, Jiamin Wen, Suning Liu, Di Wen, Wei Luo, Weihua Wang, Subba R. Palli, Li Sheng

Entomology Faculty Publications

Background Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown.

Results In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for …

The Mechanoreceptor Piezo Is Required For Spermatogenesis In Bombyx Mori, Zhongjie Zhang, Xiaojing Liu, Bo Hu, Kai Chen, Ye Yu, Chenxin Sun, Dalin Zhu, Hua Bai, Subba Reddy Palli, Anjiang Tan

Entomology Faculty Publications

Background The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm.

Results In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, …

Contemporary Vs. Traditional Dna-Based Mutation Testing To Detect Hereditary Breast And Ovarian Cancer Syndrome (Hboc) In Women: A Meta Narrative Review, Hannah Olivia Cantu, Jacob Hipp, Nyela Y. Lopez, Duc Duy Nguyen

Research Methods Poster Session 2024

No abstract provided.

Examining The Effects Of Artemisia Annua On Neuro2a Cells, Wesley Lim

Honors Undergraduate Theses

Artemisia annua L. is a well-known medicinal herb used in Traditional Chinese Medicine for many centuries and contains artemisinin, which exhibits antimalarial properties [1] and is a potential treatment for SARS-CoV-2 [2]. However, the neurological effect of A. annua and its compounds are poorly understood. We hypothesize that A. annua extracts and artemisinin will provide protection against oxidative stress in mouse neuronal Neuro2A cells. Superoxide dismutase 1 (SOD1) is an anti-oxidant enzyme that protects against oxidative damage [3]. Growth Arrest and DNA Damage-inducible 45 alpha (Gadd45a) is involved in DNA repair and is a common biomarker for DNA damage[4]. SOD1 …

Nudcl2 Is Required For Cytokinesis By Stabilizing Rcc2 With Hsp90 At The Midbody, Xiaoyang Xu, Yuliang Huang, Feng Yang, Xiaoxia Sun, Rijin Lin, Jiaxing Feng, Mingyang Yang, Jiaqi Shao, Xiaoqi Liu, Tianhua Zhou, Shanshan Xie, Yuehong Yang

Markey Cancer Center Faculty Publications

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for success- ful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mam- malian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinu- cleation, and midbody disorganization. Using iTRAQ-based …

Developing Cellular Systems To Elucidate Rna Structural Dynamics Of Cag Expansion Transcripts In Spinocerebellar Ataxias, Victoria Demeo

Electronic Theses & Dissertations (2024 - present)

Spinocerebellar ataxias (SCAs) are a diverse group of over 40 genetically heterogeneous neurodegenerative disorders, many of which are caused by a trinucleotide CAG repeat expansion in the coding region of specific genes. These expansions lead to the production of polyglutamine (polyQ) tracts that interfere with normal protein function, triggering cellular dysfunction and contributing to disease pathogenesis. The most well-known of these SCAs, such as SCA1, SCA2, and SCA3, exhibit progressive neurodegeneration, yet the precise mechanisms through which these mutations cause disease remain poorly understood.

A significant challenge in studying CAG repeat expansion disorders lies in the complexity of the disease …

Consequences Of Spatial Structure In Soil–Geomorphic Data On The Results Of Machine Learning Models, Daehyun Kim, Insang Song, Lorrayne Miralha, Daniel R. Hirmas, Ryan W. Mcewan, Tom G. Mueller, Pavel Samonil

Biology Faculty Publications

In this paper, we examined the degree to which inherent spatial structure in soil properties influences the outcomes of machine learning (ML) approaches to predicting soil spatial variability. We compared the performances of four ML algorithms (support vector machine, artificial neural network, random forest, and random forest for spatial data) against two non-ML algorithms (ordinary least squares regression and spatial filtering regression). None of the ML algorithms produced residuals that had lower mean values or were less autocorrelated over space compared with the non-ML approaches. We recommend the use of random forest when a soil variable of interest is weakly …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Cellular Mechanism Of Pentagalloyl Glucose-Mediated Prevention And Reversal Of Abdominal Aortic Aneurysms, Greg Halsey

All Dissertations

Abdominal aortic aneurysm (AAA) has been the 15th leading cause of death in persons older than 55 for the past ten years in several Western countries, with rupture resulting in an almost 100% mortality rate. AAA is a focal dilation of the aorta characterized by progressive loss of elastin and vascular smooth muscle cells (SMCs), as well as persistent inflammatory response [1]. The only treatment for AAA is surgery; however, the mortality post-procedure is still 1-4%, with a 15-30% chance of morbidity [2].

Pentagalloyl glucose (PGG) treatment is effective in the reversal of AAA. While its stabilizing interactions with extracellular …

The 14-Day Rule For In Vitro Human Embryo Research Requires Adjustment: From A Comprehensive Perspective Of Science, Ethics And Policy Research, Xiao Lu, Ming Zhao, Huihui Liu, Tianqing Li, Tao Tan, Weizhi Ji

Bulletin of Chinese Academy of Sciences (Chinese Version)

Since it was proposed, in vitro human embryo research had been following the 14-day rule, which limited in vitro research on human embryos within 14 days after fertilization. With the advancement in embryo culturing technology, this ethical rule has been greatly challenged. In 2021, the International Society for Stem Cell Research (ISSCR) recommended a conditional extension of the existing time limit in ISSCR Guidelines for Stem Cell Research and Clinical Translation, hence the international scientific community has restarted the debate on the 14-day rule. This study systematically analyzed the historical background and controversies of the 14-day rule ethical regulation of …

Use Of A Hydrogel Material For In-Vitro Vascular Applications: A Promising Approach For Medical Device Characterization., Wisdom Shadrach

ORBioM (Open Research BioSciences Meeting)

In recent years, there has been significant interest in creating more advanced in-vitro cell culture vascular models to improve pre-clinical screening of medical therapies and devices, and the expanding research field of hydrogels as a culture biomaterial holds promise to meet this need. Hydrogels are now commonly employed in various biomedical areas such as ophthalmology, drug delivery, and cardiovascular applications, and this is due to their unique properties such as biocompatibility and ability to mimic extracellular matrix (ECM). There remains a need for hydrogels with good bio-compatibility index that can serve as robust 3D in-vitro vascular culture material suitable for …

Early Development Of C3ar1-Targeting Chimeric Antigen Receptor T Cells For The Treatment Of Glioblastoma Multiforme, Cameron Fraser

Electronic Theses, Projects, and Dissertations

Glioblastoma multiforme is the most aggressive type of glioma, demonstrating extremely low long-term survival despite modern therapies. Chimeric antigen receptor T cells have shown extreme levels of success in the treatment of B cell lymphomas through persistent anti-tumor activity. Prior research has demonstrated the therapeutic potential in targeting the C3a-C3aR1 pathway as it acts in an autocrine loop, maintaining the proliferation and survival of cancer stem cells within the tumor. Here, we reorient the treatment to target C3aR1 for the treatment of glioblastoma multiforme. In order to achieve this, Jurkat immortalized T cells will express various chimeric antigen receptor designs …

Transcriptional Pausing Factor M1bp Regulates Cellular Homeostasis By Suppressing Autophagy And Apoptosis In Drosophila Eye, Anuradha Venkatakrishnan Chimata, Hannah Darnell, Akanksha Raj, Madhuri Kango-Singh

Biology Faculty Publications

During organogenesis cellular homeostasis plays a crucial role in patterning and growth. The role of promoter proximal pausing of RNA polymerase II, which regulates transcription of several developmental genes by GAGA factor or Motif 1 Binding Protein (M1BP), has not been fully understood in cellular homeostasis. Earlier, we reported that M1BP, a functional homolog of ZKSCAN3, regulates wingless (wg) and caspase-dependent cell death (apoptosis) in the Drosophila eye. Further, blocking apoptosis does not fully rescue the M1BP^RNAi phenotype of reduced eye. Therefore, we looked for other possible mechanism(s). In a forward genetic screen, members of the Jun-amino-terminal-(NH2)-Kinase (JNK) pathway …

Mirna Regulation Of Skeletal Muscle Hypertrophy, Maslyn Greene

All Dissertations

Muscle tissue is vital to animal survival and economically essential to livestock producers. Reduced muscle growth can occur from various reasons, including genetics, nutrition, and the pre and postnatal environment. Understanding the mechanisms behind muscle growth can aid in developing strategies to increase muscle mass. Several methods to increase muscle mass in livestock animals are currently being pursued, including nutrition, hormonal therapy, and genetic selection. One newly developing avenue is using miRNA technologies to change the expression of protein-coding genes. miRNA are a type of RNA that regulate over half of protein-coding gene expression. Here we evaluate muscle characteristics such …

N-Acetyltransferase 9 Ameliorates Aβ42-Mediated Neurodegeneration In The Drosophila Eye, Prajakta Deshpande, Anuradha Venkatakrishnan Chimata, Emily E. Snider, Aditi Singh, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, manifests as accumulation of amyloid-beta-42 (Aβ42) plaques and intracellular accumulation of neurofibrillary tangles (NFTs) that results in microtubule destabilization. Targeted expression of human Aβ42 (GMR > Aβ42) in developing Drosophila eye retinal neurons results in Aβ42 plaque(s) and mimics AD-like extensive neurodegeneration. However, there remains a gap in our understanding of the underlying mechanism(s) for Aβ42-mediated neurodegeneration. To address this gap in information, we conducted a forward genetic screen, and identified N-acetyltransferase 9 (Mnat9) as a genetic modifier of GMR > Aβ42 neurodegenerative phenotype. Mnat9 is known to stabilize microtubules by inhibiting c-Jun-N- …

Cytotoxic Activity Of Salvia Officinalis Extract Mediated By The Inhibition Of Jak2 In Breast Cancer, Salma Alawadi Dawood

Theses and Dissertations

Background: Breast cancer is the most common type of invasive cancer in women in their forties and fifties. Recent evidence suggests that JAK2/STAT3 signaling is constitutively active in breast cancer. Previous studies suggest that plant extracts, including Salvia Officinalis, have strong cytotoxic effects on breast cancer cells. The differential expression of miRNAs is also strongly linked to cancer development.

Aim: In the current study, we hypothesize that S. Officinalis extract suppresses JAK2 expression and has strong anticancer potential in MCF7 breast cancer cell lines.

Methods: GC-MS analysis showed the presence of flavonoids in dried leaf of …

Development Of Wiskott-Aldrich Syndrome Knock Out Protocol For Drug Substance Assay Development, Julia C. Hanna

Master's Theses

Wiskott-Aldrich Syndrome (WAS) is a rare X-linked primary immunodeficiency affecting approximately 1 in 100,000 live XY births in North America and is caused by a mutation to the WAS gene which is expressed across hematopoietic lineages. The WAS protein (WASp) plays a role in regulating actin polymerization. On a cellular level, there are a variety of effects of a lack of WASp or expression of a dysfunctional WASp protein for patients including issues with migration, adhesion, chemotactic response, phagocytosis, activation, and proliferation across different cell types in addition to reduced platelet size and output. This can lead to several systematic …

Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques.

Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients.

Methods: We selected Western blotting technique to study …

Review Of Biomedical Applications Of Cardiovascular Tissue Engineering, Natalie M. Howard

Honors College Theses

Tissue engineering can be defined as processes that aim to generate three-dimensional functional tissues in vitrothat have been favorably altered according to the structural, biochemical, electrophysiological, and biomechanical properties of the desired tissue before implantation into the human body. In relation to cardiac tissues, these properties would include the ability to conduct action potentials, withstand systolic pressure, permit sufficient O₂ and CO₂penetration, sufficient vascularization to supply nutrients for cellular activity, surface topology that enables cellular communication, and more. As heart diseases and instances of myocardial infarction continue to rise worldwide, there is an increasing need for …