Cell Biology Commons^™

Identifying The Roles Of Mir-17 In Ciliogenesis And Cell Cycle, Ashwaq Alanazi, Ayan K. Barui, Ashraf M. Mohieldin, Ankan Gupta, Ramani Ramachandran, Surya M. Nauli

Pharmacy Faculty Articles and Research

Emerging evidence suggests a significant contribution of primary cilia to cell division and proliferation. MicroRNAs, especially miR-17, contribute to cell cycle regulation and proliferation. Recent investigations have highlighted the dysregulated expression of miR-17 in various malignancies, underlining its potential role in cancer. However, the correlation between primary cilia and miR-17 has yet to be fully elucidated. The present study examines the presence of miR-17 in primary cilia. The miR-17 expression is studied in selected ciliary protein knockdown cells. Using in situ hybridization (ISH), we identified the subcellular localization of miR-17 in both cilium and cell body. We confirmed the importance …

Unraveling The Role Of Hid-1: Insights Into Sgii Regulation, Breanna L. Sellers

Electronic Theses and Dissertations

The regulated secretory pathway is important for the secretion of hormones and neuropeptides from large dense core vesicles (LDCVs). Dysregulation of the biogenesis of LDCVs can result in metabolic and neurological diseases. Recent studies have suggested that the peripheral membrane protein HID-1 plays a role in the sorting and storage of granins which contribute to LDCV biogenesis. To further understand how HID-1 influences the regulation of granins, we investigated potential HID-1 interactors. We determined that while HID-1 is likely functioning in the same pathway as USP25, a deubiquitinating enzyme (DUB), the cause of reduced cellular SgII levels is likely not …

Akt Disruption Leads To Non-Canonical Apical Constriction In Drosophila Embryos, Vincent Brown

Electronic Theses and Dissertations

The Akt/mTOR pathway (Akt pathway) has largely been examined in terms of its role as the primary nutrient sensing pathway due to its ability to recognize nutrient availability within a cell, particularly amino acids and glucose. Among its nutrient sensing characteristics, this pathway also contributes to a large variety of other cell functions such as cell growth, proliferation, protein synthesis, and cell survival via anti-apoptotic signaling. Although many aspects of this pathway have been carefully studied, the extent to which it regulates embryonic development remains unclear. Here, I examine Akt function in the early Drosophila embryo and demonstrate that Akt …

Cpsf6'S Nuclear Localization Signal Mediates Hiv-1 Intranuclear Events Following Nuclear Import, Nick Rohlfes

Dissertations

The early stages of the HIV-1 lifecycle include the trafficking of the viral capsid into the nucleus of infected cells. The viral capsid, which encloses the viral genome and accessory proteins required for reverse transcription (RT) and integration, traffics towards the nucleus and enters through the nuclear pore complex (NPC). This process is mediated through interactions between the virus and several host proteins, including cleavage and polyadenylation specificity factor 6 (CPSF6). CPSF6 is an early HIV-1 host factor which assists HIV-1 nuclear localization and post-entry integration targeting. CPSF6 contains a function nuclear localization signal (NLS), and as a result, is …

Cell-Based Medicinal Products: Progress And Perspectives, Lijian Hui, Xiang Yuan, Jingqi Wu

Bulletin of Chinese Academy of Sciences (Chinese Version)

Cell-based medicinal products are a breakthrough that has been proven to treat previously incurable diseases, making them a topic of global interest. This review delves into the current state and progress of cell therapy, highlighting the remarkable therapeutic effects of various types of cell-based medicinal products. We specifically explore the potential development of cell-based medicinal products in China, focusing on promoting clinical translation and commercialization. We propose necessary actions to achieve these goals, such as fostering cutting-edge basic research, innovative therapeutic approaches, scalable manufacturing processes, and policy changes.

Regulation Of Sterile Inflammatory Responses By Mitochondria-Associated Proteins, Meghana Venkatesan

Master's Theses

Inflammation is an important defense mechanism through which cells respond to pathogenic insults and damage/stress signals. Immune cells mediate extracellular inflammatory responses by synthesizing and releasing small proteins called cytokines, which play critical roles in modulating these responses. Specifically, key pro-inflammatory cytokines such as IL-1beta are released upon the assembly and activation of a multi-protein intracellular complex called the inflammasome, the most well-studied of which is the NLRP3 inflammasome. Several proteins have been identified as important regulators of cellular stress responses, including vacuole membrane protein 1 (VMP1). The present research shows that VMP1-depleted cells exhibit exacerbated cellular inflammation and are …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …

A Comparison Of Diploid And Triploid Eastern Oysters For Aquaculture Production Under Extreme Temperatures And Salinities, Joshua H. Kim

LSU Master's Theses

Off-bottom aquaculture of Eastern oysters (Crassostrea virginica) is a nascent industry that is increasingly supported by the use of triploid oysters, which grow faster than diploids. Despite their growth advantage, elevated triploid mortality compared to diploids under high temperature, low salinity, or a combination of these conditions challenge consistent triploid production. Identifying the environmental thresholds at which differential triploid mortality occurs and predicting its economic impact are important to informing decision-making in oyster aquaculture. The goal of this thesis was to compare the biological and economic performance of diploid and triploid oysters under high temperature and low salinity conditions. …

Investigating The Cellular Mechanisms Of Intracellular Ph Regulation During Exposure To High Co2., Dillon Flowers

Biology Theses

There are at least two different strategies of pH regulation among fish. The first is coupled pH regulation (CPR), where regulation of blood pH facilitates tissue pH regulation; and the second is preferential intracellular pH (pHi) regulation (PPR), where tissue pH remains tightly regulated despite a sustained reduction in blood pH. The cellular and molecular mechanisms underlying the differences in pHi regulation are currently unknown. I investigated the mechanisms of pH regulation in fishes using Rainbow Trout (Oncorhynchus mykiss) and Channel Catfish (Ictalurus punctatus) which use CPR and PPR, respectively. Fish were exposed to elevated CO …

Corneal Epithelial Tissue Engineering Approaches To Treat Limbal Stem Cell Deficiency, Sasirekha K

Theses and Dissertations

A clear healthy cornea is essential for visual acuity. As a self-renewing and regenerating tissue, the corneal epithelium has a stem cell pool, the limbus that acts as its proliferative reservoir. When limbal epithelial stem cells are destroyed or become dysfunctional, a pathological state known as limbal stem cell deficiency (LSCD) manifests. Damaged corneas have been successfully reconstructed by transplanting the cultured limbal epithelial stem cells. Limbal stem cell transplantation (LSCT) is one of the applicable and most challenging procedures in clinical ophthalmology for the reconstruction of the stratified ocular surface epithelium in patients with LSCD. Given the above challenge, …

Absence Of Motor Impairments Or Pathological Changes In Tmem230 Knockout Rats, Wenjuan Zhang, Hao Peng, Daihe Yang, Guohua Song, Juan He, Yun Zhou, Cao Huang, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson's disease (PD), which is the second most common neurodegenerative disorder, is characterized by progressive movement impairment and loss of midbrain dopaminergic neurons in the substantia nigra. Although mutations in TMEM230 are linked to familial PD, the pathogenic mechanism underlying TMEM230-associated PD remains to be elucidated. To explore the effect of TMEM230 depletion in vivo, we created TMEM230 knockout rats using CRISPR-Cas9 technology. TMEM230 knockout rats did not exhibit any core features of PD, including impaired motor function, loss of dopaminergic neurons in the substantia nigra, or altered expression of proteins related to autophagy, the Rab family, or vesicular trafficking. …

Assessment Of Tripeptides Self-Assembly & Er Stress On Cell Viability And Exosome Secretion In Mda-Mb231, Azmat Parveen

Theses and Dissertations

This study delves into the effects of tripeptides KYpF and WYpK(NBD) on MDA-MB-231 cells, uncovering KYpF's ability to reduce cell proliferation and exosome secretion in peptide treated cells. Conversely, WYpK(NBD) demonstrated significant toxicity at 10 μM. These insights pave the way for optimizing peptide-based cellular treatments for exosome secretion purposes.

Manipulation Of Cellular Proliferating Cell Nuclear Antigen (Pcna) During Herpes Simplex Virus Type 1 Infection, Jessica Packard, Jill A. Dembowski

Electronic Theses and Dissertations

Herpes simplex virus type 1 (HSV-1) is a double stranded DNA virus that replicates within the nucleus of host cells. Using accelerated native isolation of proteins on nascent DNA (aniPOND), cellular proteins were found to associate with HSV-1 replication forks. One host factor of interest is proliferating cell nuclear antigen (PCNA), the DNA sliding clamp that tethers DNA polymerases and DNA damage response proteins to replicating cellular DNA. Although HSV-1 encodes its own DNA polymerase processivity factor (UL42), PCNA plays a key role in HSV-1 infection. We used commercially available PCNA inhibitors and short hairpin RNAs (shRNA) to investigate how …

Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans, Stephani S. Martinez Barrera

All Dissertations

Cryptococcus neoformans is a globally distributed fungal pathogen responsible for causing cryptococcal meningitis in immunocompromised individuals. This pathogenic yeast must adapt to changes in temperature upon entering the human host. Septin proteins are conserved filament-forming GTPases that assemble as higher-order complexes at the cell cortex to support cytokinesis and morphogenesis in fungal and animal cells. In C. neoformans, four septin homologs (Cdc3, Cdc10, Cdc11, and Cdc12) assemble at the mother-bud neck, contributing to cytokinesis through poorly understood mechanisms. C. neoformans strains lacking the septins Cdc3 or Cdc12 are viable at 25°C, but fail to proliferate at 37°C, and are …

Placental Co-Transcriptional Activator Vestigial-Like 1 (Vgll1) Drives Tumorigenesis Via Increasing Transcription Of Proliferation And Invasion Genes, Heather Sonnemann

Dissertations and Theses (Open Access)

Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists. The aim of this study was to evaluate …

Vesicle-Associated Membrane Proteins In Airway Mucin Secretion, Boxuan Yang

Dissertations and Theses (Open Access)

Mucus plays a vital role in shielding the lungs against harmful substances such as particles, pathogens, and chemicals inhaled from the environment. It captures these harmful elements, and ciliary action helps to expel them from the lungs. Paradoxically, malfunctioning of mucus induces the development of various respiratory illnesses, including asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases. Despite extensive research on controlling mucin production and hydration, the process of secretion is not yet fully comprehended.

Mucin undergoes regulated secretion at two rates: a low baseline rate and a high stimulated rate. Over the past 25 years, …

Nutrient Intake And Nutritional Status Of Blood Cancer Patients At A Tertiary Hospital In India: A Cross-Sectional Descriptive Analysis Of Leukemia, Lymphoma And Multiple Myeloma, Enock Topisia, Loise Wamahiga Wang’Ondu

Haematology and Oncology, East Africa

In 2018, there were an estimated 18 million cancer cases worldwide, with lymphoma, multiple myeloma, and leukemia contributing to a significant portion of these cases. Lymphoma accounted for 79,990 cases, multiple myeloma for 159,985 cases, and leukemia for 437,033 cases globally (AICR, 2018). In the United States alone, approximately 30,770 people are diagnosed with multiple myeloma each year. Multiple myeloma comprises about 1.8% of all cancers and around 10% of all “blood cancers,” which includes leukemia (Penn Medicine, 2020). India ranks third in the highest reported cases of blood cancer, following the United States and China, affecting more than 70,000 …

Elucidation Of Molecular Mechanisms Underlying Tumor Necrosis Factor (Tnf) Release From Mast Cells, Tolulope Eunice Ayo

Dissertations

Mast cells are one of the major producers of tumor necrosis factor-alpha (TNF), and mast cell-derived TNF (MC-TNF) is associated with pathological conditions such as rheumatoid arthritis, inflammatory bowel diseases, and allergic asthma. However, the molecular machinery underlying TNF release from mast cells has been unclear, despite the conserved nature of exocytosis. To delineate the exocytic machinery required for TNF release from mast cells, we systematically dissected the exocytic fusion machinery (e.g., Munc13, Munc18, and VAMP families) expressed in mast cells, using a combination of CRISPR-dependent knockout, RNA interference, confocal microscopy, lentiviral rescue experiments, and cell-based assays. Out of the …

A Shield-Bearer’S Tale: Elucidating The Roles Of Estradiol And Choline In Mitigating Chemotherapy-Related Cognitive Impairment, Robert W. Botelho Jr.

USF Tampa Graduate Theses and Dissertations

Chemotherapy-Related Cognitive Impairments (CRCIs) are significant consequences of chemotherapy that affect a substantial portion of breast cancer survivors, potentially persisting long after treatment cessation. This series of studies investigated the neuroprotective roles of estradiol and choline against CRCIs induced by cyclophosphamide and doxorubicin (CYP/DOX), commonly known as Adriamycin/Cytoxan (AC) chemotherapy. Utilizing the MMTV-PyVT mouse model of breast cancer, this body of work spans several experimental studies, the first of which evaluates the impact of dietary choline supplementation on spatial memory and cholinergic function in tumor-bearing mice undergoing chemotherapy. The subsequent study tests whether impaired ovarian function and resulting reductions in …

Diesel Exhaust Particles Alter Mitochondrial Bioenergetics And Camp Producing Capacity In Human Bronchial Epithelial Cells, Isabella Cattani-Cavalieri, Marina Trombetta-Lima, Hong Yan, Ana L. Manzano-Covarrubias, Hoeke A. Baarsma, Asmaa Oun, Melissa Mol Van Der Veen, Emily Oosterhout, Amalia M. Dolga, Rennolds S. Ostrom, Samuel Santos Valenca, Martina Schmidt

Pharmacy Faculty Articles and Research

Introduction: Air pollution from diesel combustion is linked in part to the generation of diesel exhaust particles (DEP). DEP exposure induces various processes, including inflammation and oxidative stress, which ultimately contribute to a decline in lung function. Cyclic AMP (cAMP) signaling is critical for lung homeostasis. The impact of DEP on cAMP signaling is largely unknown.

Methods: We exposed human bronchial epithelial (BEAS-2B) cells to DEP for 24–72 h and evaluated mitochondrial bioenergetics, markers of oxidative stress and inflammation and the components of cAMP signaling. Mitochondrial bioenergetics was measured at 72 h to capture the potential and accumulative effects of …