Dysregulation Of Ryr Calcium Channel Causes The Onset Of Mitochondrial Retrograde Signaling,
2020
University of Pennsylvania
Dysregulation Of Ryr Calcium Channel Causes The Onset Of Mitochondrial Retrograde Signaling, Anindya Roy Chowdhury, Satish Srinivasan, György Csordás, György Hajnóczky, Narayan G Avadhani
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
This study shows that multiple modes of mitochondrial stress generated by partial mtDNA depletion or cytochrome c oxidase disruption cause ryanodine receptor channel (RyR) dysregulation, which instigates the release of Ca2+ in the cytoplasm of C2C12 myoblasts and HCT116 carcinoma cells. We also observed a reciprocal downregulation of IP3R channel activity and reduced mitochondrial uptake of Ca2+. Ryanodine, an RyR antagonist, abrogated the mitochondrial stress-mediated increase in [Ca2+]c and the entire downstream signaling cascades of mitochondrial retrograde signaling. Interestingly, ryanodine also inhibited mitochondrial stress-induced invasive behavior in mtDNA-depleted C2C12 cells and HCT116 carcinoma cells. In addition, co-immunoprecipitation shows reduced FKBP12 …
Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery,
2020
Marshall B. Ketchum University
Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari
Pharmacy Faculty Articles and Research
A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)5C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl3 with [(WR)5C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of [(WR) …
Phosphorylation Of Cyclophilin D At Serine 191 Regulates Mitochondrial Permeability Transition Pore Opening And Cell Death After Ischemia-Reperfusion,
2020
Thomas Jefferson University
Phosphorylation Of Cyclophilin D At Serine 191 Regulates Mitochondrial Permeability Transition Pore Opening And Cell Death After Ischemia-Reperfusion, Stephen Hurst, Fabrice Gonnot, Maya Dia, Claire Crola Da Silva, Ludovic Gomez, Shey-Shing Sheu
Department of Medicine Faculty Papers
The mitochondrial permeability transition pore (mPTP) plays a critical role in the pathogenesis of cardiovascular diseases, including ischemia/reperfusion injury. Although the pore structure is still unresolved, the mechanism through which cyclophilin D (CypD) regulates mPTP opening is the subject of intensive studies. While post-translational modifications of CypD have been shown to modulate pore opening, specific phosphorylation sites of CypD have not yet been identified. We hypothesized here that phosphorylation of CypD on a serine residue controls mPTP opening and subsequent cell death at reperfusion. We combined in silico analysis with in vitro and genetic manipulations to determine potential CypD phosphorylation …
From Development To Therapy: A Panoramic Approach To Further Our Understanding Of Cancer,
2020
University of Nebraska Medical Center
From Development To Therapy: A Panoramic Approach To Further Our Understanding Of Cancer, Brittany Poelaert
Theses & Dissertations
Solid tumors, such as pancreatic cancer, often result in dismally low survival outcomes for patients due to insufficient understanding of disease development and progression. Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and although oncogenic drivers (such as KRAS mutation or loss of tumor suppressor p53) and stages of disease development have been studied, further understanding of pancreatic cancer development is greatly needed. Studies from our laboratory have identified novel and varied functions of amyloid precursor-like protein 2 (APLP2) in the development and progression of pancreatic cancer. These functions include promoting cancer cell migration, …
Effect Of Cannabidiol And ∆9-Tetrahydrocannabinol Concentration On Breast Cancer Cell Viability,
2020
University of Northern Colorado
Effect Of Cannabidiol And ∆9-Tetrahydrocannabinol Concentration On Breast Cancer Cell Viability, Dorothy Achiaa Agyemang
Ursidae: The Undergraduate Research Journal at the University of Northern Colorado
-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids that have a potential impact in cancer treatments. Studies have shown that certain cannabinoids cause cancer cells to die, but only with selective concentrations, which have not been well documented. The first study of this thesis was to determine the exact concentration of CBD and THC needed to kill human MCF-7 breast cancer cells rather than create mass multiplication leading to more growth of the cancer. To conduct this experiment, cell culture was performed with a MCF-7 breast cancer cell line. The treatment groups were treated with CBD or THC at varying concentrations …
Npc1 Deficiency Impairs Cerebellar Postnatal Development Of Microglia And Climbing Fiber Refinement In A Mouse Model Of Niemann-Pick Disease Type C.,
2020
Rowan University
Npc1 Deficiency Impairs Cerebellar Postnatal Development Of Microglia And Climbing Fiber Refinement In A Mouse Model Of Niemann-Pick Disease Type C., Bridget R Boyle, Sierra E Melli, Ruth S Altreche, Zachary M Padron, Fawad A K Yousufzai, Sarah Kim, Mariella D Vasquez, Dawn M Carone, Benjamin Carone, Ileana Soto Reyes
College of Science & Mathematics Departmental Research
Little is known about the effects of NPC1 deficiency in brain development and whether these effects contribute to neurodegeneration in Niemann-Pick disease type C (NPC). Degeneration of cerebellar Purkinje cells occurs at an earlier stage and to a greater extent in NPC; therefore, we analyzed the effect of NPC1 deficiency on microglia and on climbing fiber synaptic refinement during cerebellar postnatal development using the
Porcine Cytokines, Chemokines And Growth Factors: 2019 Update,
2020
USDA, Agricultural Research Service
Porcine Cytokines, Chemokines And Growth Factors: 2019 Update, Harry D. Dawson, Yongming Sang, Joan K. Lunney
Agricultural and Environmental Sciences Faculty Research
Pigs are a major food source worldwide as well as major biomedical models for human physiology and therapeutics. A thorough understanding of porcine immunity is essential to prevent and treat infectious diseases, and develop effective vaccines and therapeutics. The use of pigs as biomedical models is dependent on the growing molecular and immune toolbox. This paper summarizes current knowledge of swine cytokines, chemokines and growth factors, identifying 289 pig proteins, characterizing knowledge of their gene structures and families. It identifies areas in the current swine genome build that need to be clarified. A broad-based literature and vendor search was conducted …
Effect Of S100b Deletion On Membrane Properties And Localization Of Ncald And Hpca,
2020
Rowan University
Effect Of S100b Deletion On Membrane Properties And Localization Of Ncald And Hpca, Natasha Hesketh
Graduate School of Biomedical Sciences Theses and Dissertations
Calcium signaling is particularly important for neuronal function. Neurons utilize a wide range of calcium-binding proteins. Dysregulation of such proteins is linked to neurodegeneration. Neurocalcin delta (NCALD), hippocalcin (HPCA), and S100B are calcium sensors that are expressed in the hippocampus, a brain region essential to memory and severely damaged in Alzheimer’s disease (AD). Despite the potential importance of these proteins, we do not fully understand the physiological significance of their relationship. Because NCALD and HPCA are known to interact with S100B, we hypothesized that the loss of S100B affects NCALD and HPCA localization, and therefore electrical properties, of hippocampal neurons. …
The Role Of Homologous Cyclin B’S In The Cell Cycle And, In Their Absence, The Effect On Zebrafish Early Development,
2020
Western Michigan University
The Role Of Homologous Cyclin B’S In The Cell Cycle And, In Their Absence, The Effect On Zebrafish Early Development, Tetiana Petrachkova
Dissertations
Regulation of cell division is essential for normal embryo development. The Cyclins and their Cyclin-dependent kinases are key regulators controlling this process. In this thesis, I examine the role of cyclin B1 and cyclin B2 in zebrafish development. It is thought that both Cyclins are necessary for a cell to progress past the G2/M checkpoint into mitosis. First, I show that zygotic Cyclin B1 is essential for normal cell cycle progression, but not for cells to enter mitosis. Lack of zygotic Cyclin B1 in the early arrest mutant specter, which carries a nonsense mutation in the cyclin B1 gene, …
The Investigation Of Group 1 Late Embryogenesis Abundant Protein 6 And Its Role In Arabidopsis Thaliana Desiccation Tolerance,
2020
Grand Valley State University
The Investigation Of Group 1 Late Embryogenesis Abundant Protein 6 And Its Role In Arabidopsis Thaliana Desiccation Tolerance, Joann Eise Thomson
Masters Theses
Like most seeds, Arabidopsis thaliana seed development is divided into three major phases: morphogenesis, storage deposition, and maturation drying. During maturation drying the seed becomes desiccation tolerant (DT) at some point and the seed rapidly loses water until its moisture level is approximately 10% on a fresh weight basis. The ability of the seeds to withstand this extreme water loss is hypothesized to be due, in part, to the accumulation of late embryogenesis abundant (LEA) proteins. In A. thaliana, there are 51 LEA proteins which are divided into seven groups based on amino acid sequence similarities. Group 1 LEA …
Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway,
2020
University at Albany, State University of New York
Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo
Legacy Theses & Dissertations (2009 - 2024)
The studies described here explored the role of Transforming Growth Factor Beta-1 (TGFβ1) and Signal Transducer and Activator of Transcription 3 (STAT3) as potential regulators of the Hyaluronic Acid (HA) synthesis and signaling pathway in human mammary cells. Our results support previous findings in which TGFβ1, a well characterized driver of the epithelial-mesenchymal transition (EMT) has been shown to regulate HA synthesis and signaling. Interrogation of The Cancer Genome Atlas (TCGA) indicated HAS2 expression positively correlated with TGFβ1 mRNA expression in breast cancer patients and in breast cancer cell lines. RT-qPCR experiments were used to measure the expression of the …
Epigenetic Targeting Of Mcl-1 Is Synthetically Lethal With Bcl-Xl/Bcl-2 Inhibition In Model Systems Of Glioblastoma,
2020
CUNY Bronx Community College
Epigenetic Targeting Of Mcl-1 Is Synthetically Lethal With Bcl-Xl/Bcl-2 Inhibition In Model Systems Of Glioblastoma, Enyuan Shang, Trang T. T. Nguyen, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin
Publications and Research
Apoptotic resistance remains a hallmark of glioblastoma (GBM), the most common primary brain tumor in adults, and a better understanding of this process may result in more efficient treatments. By utilizing chromatin immunoprecipitation with next-generation sequencing (CHIP-seq), we discovered that GBMs harbor a super enhancer around the Mcl-1 locus, a gene that has been known to confer cell death resistance in GBM.We utilized THZ1, a known super-enhancer blocker, and BH3-mimetics, including ABT263, WEHI-539, and ABT199. Combined treatment with BH3-mimetics and THZ1 led to synergistic growth reduction in GBM models. Reduction in cellular viability was accompanied by significant cell death induction …
Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization,
2020
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization, Chieh-Yuan Li
Dissertations and Theses (Open Access)
In recent years, technological advancements, such as next-generation sequencing and single-cell interrogation techniques, have enriched our understanding in tumor heterogeneity. By dissecting tumors and characterizing clonal lineages, we are better understanding the intricacies of tumor evolution. Tumors are represented by the presence of and dynamic interactions amongst clonal lineages. Each lineage and each cell contributes to tumor dynamics through intrinsic and extrinsic mechanisms, and the variable responses of clones to perturbations in the environment, especially therapeutics, underlie disease progression and relapse. Thus, there exists a pressing need to understand the molecular mechanisms that determine the functional heterogeneity of tumor sub-clones …
Using Novel Mouse Knockout Models To Study The Roles Of Asm (Acid Sphingomyelinase) In The Regulation Of Multiple Stem Cell Compartments In Vivo,
2020
University of Nevada, Las Vegas
Using Novel Mouse Knockout Models To Study The Roles Of Asm (Acid Sphingomyelinase) In The Regulation Of Multiple Stem Cell Compartments In Vivo, Amro Abdalla
UNLV Theses, Dissertations, Professional Papers, and Capstones
Acid Sphingomyelinase (ASM) is a lipid-modifying enzyme that breaks down sphingomyelin lipids into ceramide and phosphorylcholine. Genetic mutations in the human ASM gene leads to Niemann pick diseases (NPD) type A & B. In NPD type A, patients die between 1-2 years old due to severe neurological complications, while NPD type B patients live to adulthood but suffer from severe visceral organ complications. Type A is usually associated with complete inactivation of the ASM gene. The hallmark of NPD is Purkinje neuron (PN) death. PNs, the major neurons in the cerebellum part of the brain, regulate the balance and fine …
Comparative Analysis Of Small Non-Coding Rna And Messenger Rna Expression In Somatic Cell Nuclear Transfer And In Vitro-Fertilized Bovine Embryos During Early Development Through The Maternal-To-Embryonic Transition,
2020
Utah State University
Comparative Analysis Of Small Non-Coding Rna And Messenger Rna Expression In Somatic Cell Nuclear Transfer And In Vitro-Fertilized Bovine Embryos During Early Development Through The Maternal-To-Embryonic Transition, Jocelyn Marie Cuthbert
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
Cloning animals using somatic cell nuclear transfer (scNT) was first successfully demonstrated with the birth of Dolly the sheep, but the process of cloning remains highly inefficient. By improving our understanding of the errors that may occur during cloned cattle embryo development, we could obtain a greater understanding of how specific molecular events contribute to successful development. The central dogma of biology refers to the process of DNA being transcribed into messenger RNA (mRNA) and the translation of mRNA into proteins, which ultimately carry out the functions encoded by genes. The epigenetic code is defined as the array of chemical …
Artificial Intron Technology To Generate Conditional Knock-Out Mice,
2020
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Artificial Intron Technology To Generate Conditional Knock-Out Mice, Amber N. Thomas-Gordon
Dissertations and Theses (Open Access)
Genetic engineering has been re-shaped by the invention of new tools in modern biotechnology in a way that offers precision and efficiency in modifying the genome at a single nucleotide level and/or allowing precise control of gene expression. Such gene manipulation brings about significant findings and revelations in comprehending more about embryonic development, cellular and physiological functions, and disease pathology. Current methods used to produce conditional knockouts have limitations on conditional allele placement and modification varies among genes in different organisms. Thus, a system for generating conditional alleles with fidelity remains a challenge. My goal was to examine an approach …
Putative Roles Of Cd200 In The Leukemogenesis And Immune Evasion Of Leukemia Stem Cells,
2020
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Putative Roles Of Cd200 In The Leukemogenesis And Immune Evasion Of Leukemia Stem Cells, Shelley Herbrich
Dissertations and Theses (Open Access)
Acute myeloid leukemia (AML) stem cells (LSC) are capable of surviving current standard chemotherapy and are the likely source of deadly, relapsed disease. While stem cell transplant serves as proof-of-principle that AML LSCs can be eliminated by the immune system, the translation of existing immunotherapies to AML have been met with limited success. Consequently, understanding and exploiting the unique immune mechanisms of AML LSCs is critical. To identify novel immunotherapeutic targets, we sourced multiple large, publicly available datasets and identified CD200 as a potential stem-cell specific immune checkpoint in AML. We hypothesized that CD200 was a stem-cell specific mechanism of …
Investigating Chitosan Modified With Triethylammonium Butanamide And Triethylphosphonium Butanamide As Non-Viral Gene Delivery Vectors By Examining Cytotoxicity And Transfection Efficiency,
2020
Missouri State University
Investigating Chitosan Modified With Triethylammonium Butanamide And Triethylphosphonium Butanamide As Non-Viral Gene Delivery Vectors By Examining Cytotoxicity And Transfection Efficiency, Deborah C. Ehie
Graduate Theses/Dissertations
Gene therapy is a very challenging field, especially with new emerging genetic disorders. Chitosan (CS), due to chitosan’s flexibility, biocompatibility, and biodegradability, has been of interest in the world of gene therapy especially as researchers are gravitating towards non-viral vectors due to the problems caused by viral vectors. Nevertheless, there are still issues regarding solubility, cellular uptake of cargos being transported in vitro or in vivo, increased cytotoxicity levels, as well as many other things that prevent chitosan from being an efficient gene delivery agent. Here I present five derivatives of chitosan, which were all modified with either triethylphosphonium …
Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose.,
2020
University of Louisville
Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers
Electronic Theses and Dissertations
Our goal with this study was to gain insight into the homeostatic immune cell network in healthy adipose tissue. Specifically, we sought to determine if the immature myeloid cells found in healthy and inflamed adipose were, in fact, tissue-resident myeloid-derived suppressor cells (MDSCs). Using various in vitro and in vivo methods, we have uncovered a population of CD11bHi Ly6CHi Ly6G- MDSCs resident in healthy adipose tissue. To the best of our knowledge this is the first time that these cells have been investigated and described in healthy adipose tissue. Systemic MDSC depletion lead to the accumulation of …
A Novel Role For Rassf1a In The Regulation Of Ras Activation.,
2020
University of Louisville
A Novel Role For Rassf1a In The Regulation Of Ras Activation., Desmond Ramón Harrell Stewart
Electronic Theses and Dissertations
Ras is the most frequently activated oncogene in human cancer. It is not only the most frequently mutated oncogene, but is also rendered hyperactive in the wild-type form by aberrant regulation. Ras drives transformation and contributes to tumor aggressiveness by activating multiple downstream mitogenic effectors. Ras also possesses the paradoxical ability to induce apoptosis and senescence. Ras-induced apoptosis is not well understood, but has been largely attributed to the RASSF tumor suppressors, particularly RASSF1A. RASSF1A mediates Ras-induced apoptosis by activating pro-apoptotic proteins such as the MST kinases and BAX. RASSF1A is among the most frequently inactivated tumor suppressors in human …
