Cell and Developmental Biology Commons^™

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 …

Differential Effect Of An Evolving Amyloid And Tau Pathology On Brain Phospholipids And Bioactive Lipid Mediators In Rat Models Of Alzheimer-Like Pathology, Sonia Do Carmo, Marie Audrey I. Kautzmann, Surjyadipta Bhattacharjee, Bokkyoo Jun, Carolyn Steinberg, Joshua T. Emmerson, Janice C. Malcolm, Quentin Bonomo, Nicolas G. Bazan, A. Claudio Cuello

School of Graduate Studies Faculty Publications

Background: Brain inflammation contributes significantly to the pathophysiology of Alzheimer’s disease, and it is manifested by glial cell activation, increased production of cytokines/chemokines, and a shift in lipid mediators from a pro-homeostatic to a pro-inflammatory profile. However, whether the production of bioactive lipid mediators is affected at earlier stages, prior to the deposition of Aβ plaques and tau hyperphosphorylation, is unknown. The differential contribution of an evolving amyloid and tau pathology on the composition and abundance of membrane phospholipids and bioactive lipid mediators also remains unresolved. Methods: In this study, we examined the cortical levels of DHA- and AA-derived bioactive …

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 …

Genetics Of Mdh In Humans, Adam Haberman, Celeste N. Peterson

Biology: Faculty Scholarship

Malate dehydrogenase (MDH) performs key roles in metabolism, but little is known about its function specifically in human health and disease. In this minireview, we describe the incomplete state of our knowledge of human MDH genetics. Humans have three MDH genes with a total of four validated isoforms. MDH1 and MDH2 are widely expressed, while MDH1B is only expressed in a small subset of tissues. Many mutations in MDH1 and MDH2 have been identified in patients, but only a few have been studied to determine what symptoms they cause. MDH1 has been associated with cancer and a neurodevelopmental disorder. MDH2 …

Role Of Sds-22/Pp1 Phosphatase In Polarizing The Germplasm Of Caenorhabditis Elegans Embryo, Aparna Nurni Ravi

Dartmouth College Ph.D Dissertations

During asymmetric cell division, cell polarity and cell cycle are tightly coupled to ensure robust segregation of cell fate determinants and generation of cellular diversity. In the one-cell C. elegans embryo, multiple cell cycle kinases regulate cell polarization and posterior segregation of germline fate determinants (germplasm). For example, PLK-1 kinase inhibits the retention of its germplasm substrate POS-1 in the anterior, driving POS-1 segregation to the posterior (Han et al., 2018). Additionally, MBK-2 kinase disassembles P granules in the anterior through phosphorylation of the P granule scaffold MEG-3, helping to drive P granule segregation to the posterior (Wang et al., …

Functional And Structural Analysis Of The Neimann-Pick Disease Type C Pathway To Include Caveolin-1, Anthony Michael Seat

Chemistry and Chemical Biology ETDs

Human disease is often thought of as an all or nothing prospect, either one has the disease or one does not. This does not bear out in clinical or personal experiences, instead demonstrating that disease occurs within a spectrum ranging from presumed unaffected to demonstrably and detrimentally affected.Neimann-Pick disease is one example of this spectrum look into diseased states, with multiple named versions of a phenotypically similar disease. We focus on Neimann-Picktype C (NPC), which is the result of a disruption in the efflux of cholesterol and sphingolipids from the endocytic pathway. NPC demonstrates this concept of a spectrum of …

Evidence-Based Prostate Cancer Screening Interventions For Black Men: A Systematic Review, Abigail Lopez, Jared T. Bailey, Dorothy Galloway, Leanne Woods-Burnham, Susanne B. Montgomery, Rick Kittles, Dede K. Teteh-Brooks

Health Sciences and Kinesiology Faculty Articles

Abstract

Prostate cancer is the second leading cause of death for men in the U.S. and Black men are twice as likely to die from the disease. However, prostate cancer, if diagnosed at an earlier stage, is curable. The purpose of this review is to identify prostate cancer screening clinical trials that evaluate screening decision-making processes of Black men.

Methods

The databases PubMed, Ovid MEDLINE, CINAHL Plus, and PsychInfo were utilized to examine peer-reviewed publications between 2017 and 2023. Data extracted included implementation plans, outcome measures, intervention details, and results of the study. The Critical Appraisal Skills Programme was used …

Wee1 And Cell Size Control In Fission Yeast By The Protein Kinase Cdr2, Rachel Berg-Murante

Dartmouth College Ph.D Dissertations

The mechanisms that govern cell size have long been topics of study in the field of cell biology. In eukaryotic cells this size control is tied to checkpoints, a set threshold of minimum necessary growth linked to cyclin dependent kinase activity regulation. In the fission yeast Schizosaccharomyces pombe, the Cdk1 regulatory network is conserved, and G2/M represents the major size checkpoint. Prior to mitosis, Cdk1 is inhibited by phosphorylation applied by Wee1 during G2 phase. Once S. pombe cells have satisfied the size checkpoint, Cdk1 is activated through dephosphorylation by Cdc25. Wee1 is a dose-dependent regulator of mitotic entry …

Five Side Populations Isolated From Rat Bone Marrow‑Derived Mesenchymal Stem Cells, Dalia Al Saied Moustafa Ahmed, Mahmoud Elhussiny Salama, Ahmed Abdou Emam, Sara Mohamed Farrag, Basma Hamed Othman, Shaimaa Hassan Haiba, Mohamed Mosaad Salama

Faculty Journal Articles

Over the past decade, there has been marked enthusiasm surrounding the potential application of mesenchymal stem cells (MSCs) as universally compatible donor cells in the field of regenerative medicine. Due to their distinctive immune-tolerant characteristics, these entities hold promise for potential applications in cell replacement, gene therapy and immunomodulatory therapy. MSCs have been defined and characterized based on adhesion properties and different surface markers that are negative for hematopoietic stem cells and positive for MSCs, and their capacity for differentiation into osteocyte, chondrocyte and adipocyte is observed under suitable circumstances. However, this protocol is costly and time-consuming and cannot confirm …

Development Of Anti-Fibrotic Agents For Potential Use In Glaucoma Filtration Surgery To Prevent Scar Formation, Nikhala Shree S

Theses and Dissertations

Glaucoma is the second leading cause of blindness with irreversible vision loss. It is marked by the degeneration of retinal ganglion cells, which results in optic nerve head damage. Intraocular pressure (IOP) is a prime risk factor of glaucoma controlled by various treatment regimens i.e., medication, laser, and/ or surgery. It is reported that longterm exposure to anti-glaucoma medications (AGM) may subtle the surgical success rate leading to postoperative fibrosis. Transforming growth factor beta (TGF-β) is a growth factor that plays an important role in the development of glaucoma and promotes fibrosis.

This study is aimed at developing peptides to …

Burnout Among Medical Residents, Coping Mechanisms And The Perceived Impact On Patient Care In A Low/ Middle Income Country, Charles Muteshi, Elizabeth Ochola, Dorothy Kamya

Obstetrics and Gynaecology, East Africa

Background: Burnout is a syndrome that result from chronic workplace stress and it characterized by emotional exhaustion, depersonalization and low personal accomplishments. Studies report higher burnout levels in medical personnel compared to the general population. Workplace burnout has been directly linked to medical errors and negative coping strategies such as substance abuse. The aims of this study were to assess the level of burnout in medical residents, evaluate their impressions about coping mechanisms and assess perceived impact on patient care in a low/ middle income country setting.

Methods: This was a cross sectional, mixed methods survey carried out at Aga …

Interleukin 24 Induces Apoptosis Through Glycogen Synthase Kinase-3 Beta Inactivation In Prostate Cancer Cells, Sual J. Lopez, Moira Sauane

Theses and Dissertations

Interleukin 24 (IL-24) is a tumor-suppressing protein currently in clinical trials. IL-24 induces cancer-specific apoptosis by activating endoplasmic reticulum (ER) stress and mitochondria dysfunction. We have previously demonstrated that IL-24 leads to apoptosis in cancer cells by protein kinase A (PKA) activation in human breast cancer cells. To further understand the mechanism by which IL-24 induces apoptosis, I analyzed the role of glycogen synthase kinase-3 (GSK3), a highly conserved and normally active serine/threonine kinase in cancer cells and downstream target of PKA. The work reported here provides direct evidence that GSK3 was inhibited following IL-24 treatment in human prostate cancer …

Ceramide-Mediated Orchestration Of Oxidative Stress Response Through Filopodia-Derived Small Extracellular Vesicles, Zainuddin Quadri, Ahmed Elsherbini, Simone M. Crivelli, Salim S. El-Amouri, Priyanka Tripathi, Zhihui Zhu, Xiaojia Ren, Liping Zhang, Stefka D. Spassieva, Mariana N. Nikolova‑Karakashian, Erhard Bieberich

Markey Cancer Center Faculty Publications

Extracellular vesicles (EVs) are shed from the plasma membrane, but the regulation and function of these EVs remain unclear. We found that oxidative stress induced by H 2 O 2 in Hela cells stimulated filopodia formation and the secretion of EVs. EVs were small (150 nm) and labeled for CD44, indicating that they were derived from filopodia. Filopodia-derived small EVs (sEVs) were enriched with the sphingolipid ceramide, consistent with increased ceramide in the plasma membrane of filopo- dia. Ceramide was colocalized with neutral sphingomyelinase 2 (nSMase2) and acid sphingomyelinase (ASM), two sphingomyelinases generating ceramide at the plasma membrane. Inhibition of …

Soxb1 Transcription Factors Are Essential For Initiating And Maintaining Neural Plate Border Gene Expression, Elizabeth Schock, Joshua R. York, Austin P. Li, Ashlyn Y. Tu, Carole Labonne

Markey Cancer Center Faculty Publications

SoxB1 transcription factors (Sox2/3) are well known for their role in early neural fate specification in the embryo, but little is known about functional roles for SoxB1 factors in non-neural ectodermal cell types, such as the neural plate border (NPB). Using Xenopus laevis, we set out to determine whether SoxB1 transcription factors have a regulatory function in NPB formation. Here, we show that SoxB1 factors are necessary for NPB formation, and that prolonged SoxB1 factor activity blocks the transition from a NPB to a neural crest state. Using ChIP-seq, we demonstrate that Sox3 is enriched upstream of NPB genes in …

A Probabilistic Approach To Estimate The Temporal Order Of Pathway Mutations Accounting For Intra-Tumor Heterogeneity, Menghan Wang, Yanqi Xie, Jinpeng Liu, Austin Li, Li Chen, Arnold Stromberg, Susanne Arnold, Chunming Liu, Chi Wang

Markey Cancer Center Faculty Publications

The development of cancer involves the accumulation of somatic mutations in several essential biological pathways. Delineating the temporal order of pathway mutations during tumori- genesis is crucial for comprehending the biological mechanisms underlying cancer development and identifying potential targets for therapeutic intervention. Several computational and statistical methods have been introduced for estimating the order of somatic mutations based on mutation profile data from a cohort of patients. However, one major issue of current methods is that they do not take into account intra-tumor heterogeneity (ITH), which limits their ability to accurately discern the order of pathway mutations. To address this …

Use Of Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands And Berberine Chloride As Anti-Cancer Agents Against Triple Negative Breast Cancer, Duaa Rashad Alajroush

Chemistry & Biochemistry Theses & Dissertations

It is a worrying fact that chemotherapeutic options for treating triple negative breast cancer are limited in nature, including the use of inorganic pharmaceuticals such as cisplatin and its analogues. It has been reported that cisplatin has undesirable side effects when used as a chemotherapeutic drug. As such, there is a need to use non-platinum-containing complexes as chemotherapeutic agents. Based on that issue, it has been reported by our research group and others that cobalt- and copper-containing complexes have shown great potential in anti-cancer properties when compared to cisplatin. In this research project, the cytotoxic effects of the following complexes: …

Causes And Consequences Of Mitotic Chromosome Missegregation In Human Pluripotent Stem Cells, Chenhui Deng

Dartmouth College Ph.D Dissertations

Mitosis is a fundamental process that ensures the equal distribution of replicated chromosomes, which carry an organism's genetic material, into two daughter cells. The fidelity of mitosis is paramount, as errors in chromosome segregation result in aberrant chromosome numbers, including gains or losses, a state termed aneuploidy. Aneuploidy impacts a broad range of human conditions, including being one of the major hurdles in early human development where it is the primary cause of miscarriages and birth defects. Strikingly, more than 70% of human preimplantation embryos are aneuploid with mitotic chromosome segregation errors being the most common source of aneuploidy. However, …

T. Boudieri Extract Potentiates The Effects Of Capecitabine Treatment In Human Colon Cancer Cells, Katia Sawaya, Mahmoud Khalil, Ghada Khawaja

BAU Journal - Science and Technology

Resistance to chemotherapy remains a major challenge for colorectal cancer patients worldwide, hence the persistent need to uncover alternative treatments as well as new adjunct therapies in the fight against cancer. Natural extracts constitute an excellent source of bioactive substances that have a promising potential in that regard, with minimal negative side effects. We have previously demonstrated that both the ethanolic as well as the water extracts of Terfezia boudieri, a black desert truffle abundant in and part of the cuisine of the Mediterranean region, have significant antiproliferative effects against colon cancer cells. Our aim in this study was …

Functional Studies Of Dcaf14 In Replication Fork Stability And Genome Integrity, Neysha Tirado-Class

USF Tampa Graduate Theses and Dissertations

The response to replication stress is critical for ensuring the stability of replication forks and preserving genome integrity. To aid this response, several factors are recruited to stalled replication forks to prevent irreversible collapse of the replication machinery. Replication fork proteomic analyses of stalled forks reveal enrichment of DCAF14, a component of the Cullin4-RING (CRL4) E3 ubiquitin ligase complex, that mediates replication fork protection by blocking nuclease-mediated digestion of nascent DNA. However, little is known about the molecular mechanism by which DCAF14 functions in the context of replication stress. Notably, loss of function mutations in DCAF14 are associated with a …