Nucleic Acids, Nucleotides, and Nucleosides Commons^™

Reverse Micelles Produce Hydroxyapatite Nanoparticles As More Efficient Gene Delivery Carriers Than Regular Micelles, Vuk Uskoković

Administration and Staff Articles and Research

Hydroxyapatite (HAp) is an effective inorganic gene delivery carrier due to its ability to transport genetic cargo across cell membranes, protect it from proteolysis, and enable escape from late endosomes via pH-controlled dissolution. However, its transfection efficiency remains lower than that of viral agents, prompting studies of hybrids with cationic molecules or phases to enhance the gene delivery performance. This study reports on the synthesis of HAp in regular and reverse micellar regions of a ternary microemulsion system composed of cetyltrimethylammonium bromide (CTAB), 1-hexanol and water. Spectroscopic characterization revealed that CTAB headgroups adopted more ordered supramolecular conformations in reverse micelles …

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …

Opa1 And Disease-Causing Mutants Perturb Mitochondrial Nucleoid Distribution, J. Macuada, I. Molina-Riquelme, G. Vidal, N. Pérez-Bravo, C. Vásquez-Trincado, G. Aedo, D. Lagos, P. Yu-Wai-Man, R. Horvath, T. J. Rudge, B. Cartes-Saavedra, V. Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Optic atrophy protein 1 (OPA1) mediates inner mitochondrial membrane (IMM) fusion and cristae organization. Mutations in OPA1 cause autosomal dominant optic atrophy (ADOA), a leading cause of blindness. Cells from ADOA patients show impaired mitochondrial fusion, cristae structure, bioenergetic function, and mitochondrial DNA (mtDNA) integrity. The mtDNA encodes electron transport chain subunits and is packaged into nucleoids spread within the mitochondrial population. Nucleoids interact with the IMM, and their distribution is tightly linked to mitochondrial fusion and cristae shaping. Yet, little is known about the physio-pathological relevance of nucleoid distribution. We studied the effect of OPA1 and ADOA-associated mutants on …

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 …

Elucidating Mechanisms Of Enhanced Dsrna-Nanophytoglycogen Innate Immune Responses In Healthy Human Cells, Nicholas Jadaa

Theses and Dissertations (Comprehensive)

Immunostimulatory nucleic acids, such as long double-stranded RNA (ds)RNA, can stimulate innate immune responses in a non-sequence specific manner. These molecules are recognized by pattern-recognition receptors in the cytoplasm, endosome, and on the cell surface. Activation leads to the production of mediators of innate immune pathways, including type I interferon and proinflammatory cytokines. Although these receptors are present in all cells, their role in non-immune cells is often overlooked due to their lower level of responsiveness. Nanocarriers can enhance these nucleic acid-mediated responses, allowing for exploration of innate immune pathways in non-immune cells. Nanoparticles as carriers of nucleic acids can …

Multi-Target Ligand-Guided Selection (Ligs) Against B-Cell Specific Antigens Expressed In A Single Lymphoma Cell Population, Nicole B. Williams

Dissertations, Theses, and Capstone Projects

Nucleic acid ligands called aptamers are single-stranded DNA or RNA molecules which fold into functional three-dimensional structures to facilitate their target binding with high affinity and specificity. The method used to generate aptamers is an in vitro process called Systematic Evolution of Ligands by Exponential enrichment (SELEX). A variant of SELEX, cell-SELEX has been used to select aptamers against cell-surface proteins in their native state. We recently introduced a novel method called Ligand-Guided Selection (LIGS) to identify aptamers against cell-surface markers. Herein, we expanded LIGS method into a multiplexing platform to partition multiple aptamers against B-cell-specific antigens, CD19 and CD20, …

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …

Vitamin C Contributes To Epigenetic Regulation Of Genes Related To Diabetic Retinopathy In Retinal Endothelial Cells, Elizabeth L. Turner, Jonathon Reynolds, Walker Kay, Marianne Becnel, Matthew Conway, Alexander Kim, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

A Study Of Cobalt (Iii) Oxide Nanoparticle Delivery Of Sirna Molecules Directed Against Signaling Intermediates Of The P2y2 Receptor, Rachel Blair Stroud

Graduate Theses/Dissertations

G protein-coupled receptors are evolutionarily ubiquitous sensors of extracellular signals, propagating intracellular signal cascades through heterotrimeric G proteins. P2Y₂ receptors are GPCRs which are activated by extracellular nucleotides to mediate signaling cascades via Gαq coupling. Many GPCRs are subject to a common mechanism for signal termination involving phosphorylation of the C-terminal tail followed by β-arrestin binding and subsequent endocytic internalization of the complex. This effect has been described for the P2Y₂ R in the 1321N1 astrocytoma cell line, and UTP-induced activation and desensitization profiles have been previously defined. There is need to develop molecular vehicles for safe and …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Modification Of The Ribosome As Part Of The Adaptive Response To Oxidative Stress In Yeast, Jessica A Zinskie, Daniel Shedlovskiy, Ethan Gardner, Dimitri G Pestov, Natalia Shcherbik

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Living organisms are constantly exposed to a variety of environmental and internal stressors tha tare detrimental to their cellular physiology and viability. One such condition, oxidativestress, is caused by abnormal amounts of Reactive Oxygen Species (ROS) that can lead to damage to proteins, nucleic acids, and lipids. Although the mechanisms to neutralize ROS have been widely studied, the understanding of ROS‐mediated signaling for these mechanisms is rather incomplete and sparse. We have uncovered a previously undescribed phenomenon of yeast ribosomes to respond to elevated levels of ROS through a specific endonucleolytic cleavage of the 25S rRNA in the c‐loop of …

Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han

Pharmacy Faculty Articles and Research

The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no …

Human Anatomy And Physiology Preparatory Course: Part 1 Of 4 (Interactive), Carlos Liachovitzky

Open Educational Resources

The overall purpose of these preparatory course set of learning objectives is to help students familiarize with some terms and some basic concepts they will find later in the Human Anatomy and Physiology I course.

These 40+ learning objectives to prepare for Human Anatomy and Physiology can be downloaded and played in a desktop, or laptop (windows exe file).

The entire course has four parts:

• Part 1
• Part 2
• Part 3
• Part 4

Each learning objective is followed by a set of multiple choice question similar to those found later in a Human Anatomy and Physiology course.

The organization and …

Human Anatomy And Physiology Preparatory Course (1st Edition), Carlos Liachovitzky

Open Educational Resources

The overall purpose of this preparatory course textbook is to help students familiarize with some terms and some basic concepts they will find later in the Human Anatomy and Physiology I course.

The organization and functioning of the human organism generally is discussed in terms of different levels of increasing complexity, from the smallest building blocks to the entire body. This Anatomy and Physiology preparatory course covers the foundations on the chemical level, and a basic introduction to cellular level, organ level, and organ system levels. There is also an introduction to homeostasis at the beginning.

A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel

CMC Senior Theses

The field of stem cell research has been growing more because of the interest in using stem cells to cure diseases and heal injuries. Human embryonic stem cells, because of the controversy surrounding them—and subsequently the difficulties in acquiring samples of the existing aging cell lines—can only be used in limited capacities. While the development of induced pluripotent stem cells in the last decade has allowed the field to progress closer to medical treatments, the low efficiency of reprogramming a somatic cell to a pluripotent state, and the vast molecular and genomic differences between human embryonic stem cells and human …

Different Requirements Of The Swi/Snf Complex For Robust Nucleosome Displacement At Promoters Of Heat Shock Factor And Msn2- And Msn4-Regulated Heat Shock Genes, Tamara Y. Erkina, P. A. Tschetter, Alexander M. Erkine

Scholarship and Professional Work – COPHS

The stress response in yeast cells is regulated by at least two classes of transcription activators—HSF and Msn2/4, which differentially affect promoter chromatin remodeling. We demonstrate that the deletion of SNF2, an ATPase activity-containing subunit of the chromatin remodeling SWI/SNF complex, eliminates histone displacement, RNA polymerase II recruitment, and heat shock factor (HSF) binding at the HSP12 promoter while delaying these processes at the HSP82 and SSA4 promoters. Out of the three promoters, the double deletion of MSN2 and MSN4 eliminates both chromatin remodeling and HSF binding only at the HSP12 promoter, suggesting that Msn2/4 activators are primary determinants of …