Role Of Macrophages In Muscle Transfection With Pdna/Pluronic Formulation,
2015
University of Nebraska Medical Center
Role Of Macrophages In Muscle Transfection With Pdna/Pluronic Formulation, Vivek Mahajan
Theses & Dissertations
Non-ionic amphiphilic block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), Pluronics, arranged in a tri-block structure PEO-PPO-PEO, have raised a considerable interest in skeletal muscle Gene Therapy. Previous studies have demonstrated that co-administration of Pluronics with naked plasmid DNA (pDNA) by direct i.m. injection enhanced transgene expression not only in muscle but also in distal lymphoid organs (spleen and lymph nodes) and this response was strain-dependent; not observed in athymic (BALB/c nu/nu) mouse; suggesting a role of immune cells in gene transfer to skeletal muscles. Therefore, we first evaluated the role of inflammation and inflammatory cells, on muscle …
Functional Characterization Of The Roles Of Endocytic Recycling Regulator Ehd1 Using In Vivo And In Vitro Analyses,
2015
University of Nebraska Medical Center
Functional Characterization Of The Roles Of Endocytic Recycling Regulator Ehd1 Using In Vivo And In Vitro Analyses, Priyanka Arya
Theses & Dissertations
Endocytic recycling is a fundamental cellular process that allows the precise regulation of the membrane components and receptors at the cell surface. Recent studies have established that the C-terminal Eps15 homology domain-containing (EHD) proteins function as key regulators of this process. Four highly-conserved members of the EHD protein family in mammals, EHD1-EHD4, play shared as well as unique roles in endocytic trafficking. Studies presented here demonstrate a critical role of EHD1 in the normal ocular development in mice. Ehd1 knockout mice generated in our laboratory displayed gross ocular phenotypes including the anophthalmia, microphthalmia, and congenital cataracts. Hematoxylin and eosin (H&E) …
Analysis Of Mitochondrial Turnover In Neuromuscular Junctions Of Parkin Mutants,
2015
Purdue University
Analysis Of Mitochondrial Turnover In Neuromuscular Junctions Of Parkin Mutants, Kenny Nguyen, Hyun Sung, Peter J. Hollenbeck
The Summer Undergraduate Research Fellowship (SURF) Symposium
The accumulation of dysfunctional or damaged mitochondria in neurons has been linked to the pathogenesis of many neurodegenerative diseases, such as Parkinson’s disease. It has been proposed that proteins PINK1 and Parkin regulate mitochondrial quality control by selectively targeting depolarized mitochondria for autophagic degradation, a process known as mitophagy. Though previously analyzed in the cell bodies and axons of neurons, the role of the PINK1/Parkin pathway in the synapse is unclear, and it is not known whether mitochondrial turnover occurs in the neuromuscular junctions (NMJs). To study this, intact Drosophila nervous systems were analyzed in vivo by performing gentle dissections …
Viewing The Extracellular Matrix: An Imaging Method For Tissue Engineering,
2015
Purdue University
Viewing The Extracellular Matrix: An Imaging Method For Tissue Engineering, Michael Drakopoulos, Sarah Calve
The Summer Undergraduate Research Fellowship (SURF) Symposium
The field of regenerative medicine seeks to create replacement tissues and organs, both to repair deficiencies in biological function and to treat structural damage caused by injury. Scaffoldings mimicking extracellular matrix (ECM), the structure to which cells attach to form tissues, have been developed from synthetic polymers and also been prepared by decellularizing adult tissue. However, the structure of ECM undergoes significant remodeling during natural tissue repair, suggesting that ECM-replacement constructs that mirror developing tissues may promote better regeneration than those modeled on adult tissues. This work investigated the effectiveness of a method of viewing the extracellular matrix of developing …
Detection Of Ubiquitination On Syk And Documenting Syk Stability,
2015
Purdue University
Detection Of Ubiquitination On Syk And Documenting Syk Stability, Izabela Mazur, Wen Horng Wang, Robert J. Geahlen
The Summer Undergraduate Research Fellowship (SURF) Symposium
Post-translational modifications regulate the activities of proteins important to numerous diseases. Spleen Tyrosine Kinase (Syk) is particularly interesting to researchers because it modifies many targets and plays multiple roles in regulating cells in our bodies and its abnormal modifications may contribute to cancer, Alzheimer’s disease and allergies. In an attempt to study these modifications of Syk, we first looked at detecting ubiquitination on Syk protein. Ubiquitin, a small 8 kDa molecule, attaches to lysine residues on protein. The attachment of ubiquitin to Syk may cause Syk to either propagate signals onwards to activate other proteins or signal it to undergo …
Characterization Of Putative Wnt3a-Inducible Enhancers,
2015
California Polytechnic State University - San Luis Obispo
Characterization Of Putative Wnt3a-Inducible Enhancers, Katelynn C. Lee, Nicholas Hum, Aimy Sebastian, Gabriela Loots
STAR Program Research Presentations
The Wnt signaling pathway has been previously shown to play a major role in regulating bone metabolism and it is emerging as a target for the therapeutic intervention of bone thinning disorders such as osteoporosis. Several Wnt proteins have been shown to be expressed in bone and mutations in Wnt pathway members such as Wnt co-receptor Lrp5 and Wnt inhibitor Sost have been shown to be associated with low or high bone mass disorders, however, very little is known about specific roles played by different Wnt ligands in bone development, repair and remodeling. To identify downstream targets of Wnt signaling …
Hippocalcin Response To Calcium: Do Conserved Tryptophans – W30 Or W103 – Matter?,
2015
Rowan University
Hippocalcin Response To Calcium: Do Conserved Tryptophans – W30 Or W103 – Matter?, Sunkesula K. Sagar
Graduate School of Biomedical Sciences Theses and Dissertations
Changes in intracellular calcium levels play a very important role in cell signaling, in turn, affecting neuronal functions such as memory, learning and cell death. A class of proteins called Neuronal Calcium Sensor (NCS) proteins serves to modulate the functioning of the neuronal cells in response to changes in calcium levels, and prevent neuronal apoptosis. Structurally, all NCS proteins have 4 calcium-binding EF hand motifs, although EF1 does not bind to calcium in many members. All NCS proteins have an acyl modification at the N- terminus – where a myristoyl group is added post-translationally. Hippocalcin (HPCA) is an NCS protein, …
Beyond Bivariate Correlations: Three-Block Partial Least Squares Illustrated With Vegetation, Soil, And Topography,
2015
University of Kentucky
Beyond Bivariate Correlations: Three-Block Partial Least Squares Illustrated With Vegetation, Soil, And Topography, Daehyun Kim, Thomas J. Dewitt, César S. B. Costa, John A. Kupfer, Ryan W. Mcewan, J. Anthony Stallins
Biology Faculty Publications
Ecologists, particularly those engaged in biogeomorphic studies, often seek to connect data from three or more domains. Using three-block partial least squares regression, we present a procedure to quantify and define bi-variance and tri-variance of data blocks related to plant communities, their soil parameters, and topography. Bi-variance indicates the total amount of covariation between these three domains taken in pairs, whereas tri-variance refers to the common variance shared by all domains. We characterized relationships among three domains (plant communities, soil properties, topography) for a salt marsh, four coastal dunes, and two temperate forests spanning several regions in the world. We …
Direct Regulation Of Apoptosis By Linear Ubiqutin Chain Assembly Complex (Lubac) And Feedback Regulation Of Lubac Function By Caspases,
2015
The University of Texas Graduate School of Biomedical Sciences at Houston
Direct Regulation Of Apoptosis By Linear Ubiqutin Chain Assembly Complex (Lubac) And Feedback Regulation Of Lubac Function By Caspases, Donghyun Joo
Dissertations and Theses (Open Access)
Tumor Necrosis Factor-alpha (TNF-α) is a cytokine that plays a role in various cellular processes such as proliferation, differentiation (mainly through NF-κB signaling) and death (via apoptosis signaling). Recently, linear ubiquitination by LUBAC (linear ubiquitin chain assembly complex) was reported to have a regulatory function in TNF-α mediated NF-κB activation. Although LUBAC is suggested to control not only NF-kB signaling but also the apoptosis pathway, the precise mechanism of apoptosis regulation remains unknown. Moreover, NF-κB and apoptosis pathways have opposed but fundamental functions for various cellular processes. Although these two pathways actively interplay to balance the death and survival, the …
Histone H3 K4 Methylation Regulates The Spindle Assembly Checkpoint Through Direct Binding Of Multiple Checkpoint Components And Cdc20,
2015
The University of Texas Graduate School of Biomedical Sciences at Houston
Histone H3 K4 Methylation Regulates The Spindle Assembly Checkpoint Through Direct Binding Of Multiple Checkpoint Components And Cdc20, Andria C. Schibler
Dissertations and Theses (Open Access)
Histone H3K4 methylation is conserved across species and is associated with active transcription. By using Saccharomyces cerevisiae, we found histone H3K4 methylation has a previously unknown role in regulating mitosis through the Spindle Assembly Checkpoint. The Spindle Assembly Checkpoint ensures duplicated chromosomes are segregated correctly and each daughter cell receives one full copy of the genome. Our data show SET1 mutants and histone H3K4 mutants display a resistance to the mitotic poison, benomyl. Moreover methylated histone H3 directly binds to Spindle Assembly Checkpoint proteins Bub3 and Mad2 as well as the activator of the Anaphase Promoting Complex (APC) protein …
Activation Of Protein Kinase C And Protein Kinase D In Human Natural Killer Cells: Effects Of Tributyltin, Dibutyltin, And Tetrabromobisphenol A,
2015
Tennessee State University
Activation Of Protein Kinase C And Protein Kinase D In Human Natural Killer Cells: Effects Of Tributyltin, Dibutyltin, And Tetrabromobisphenol A, Krupa Rana, Margaret Whalen
Chemistry Faculty Research
Up to now, the ability of target cells to activate protein kinase C (PKC) and protein kinase D (PKD) (which is often a downstream target of PKC) has not been examined in natural killer (NK) lymphocytes. Here we examined whether exposure of human NK cells to lysis sensitive tumor cells activated PKC and PKD. The results of these studies show for the first time that activation of PKC and PKD occurs in response to target cell binding to NK cells. Exposure of NK cells to K562 tumor cells for 10 and 30 min increased phosphorylation/activation of both PKC and PKD …
Polyq-Dependent Rna–Protein Assemblies Control Symmetry Breaking,
2015
Dartmouth College
Polyq-Dependent Rna–Protein Assemblies Control Symmetry Breaking, Changhwan Lee, Patricia Occhipinti, Amy S. Gladfelter
Dartmouth Scholarship
Dendritic growth in fungi and neurons requires that multiple axes of polarity are established and maintained within the same cytoplasm. We have discovered that transcripts encoding key polarity factors including a formin, Bni1, and a polarisome scaffold, Spa2, are nonrandomly clustered in the cytosol to initiate and maintain sites of polarized growth in the fungus Ashbya gossypii. This asymmetric distribution requires the mRNAs to interact with a polyQ-containing protein, Whi3, and a Pumilio protein with a low-complexity sequence, Puf2. Cells lacking Whi3 or Puf2 had severe defects in establishing new sites of polarity and failed to localize Bni1 protein. Interaction …
Aspirin Triggered Resolution Phase Interaction Product D1: A Novel Treatment For Hyperoxic Acute Lung Injury,
2015
University of South Florida
Aspirin Triggered Resolution Phase Interaction Product D1: A Novel Treatment For Hyperoxic Acute Lung Injury, Ruan Rollin Cox, Jr.
USF Tampa Graduate Theses and Dissertations
Acute Lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are respiratory maladies that present immense clinical challenges. ALI affects 200,000 individuals annually and features a 40% mortality rate. ALI can be initiated by both pathogenic and sterile insults originating locally in the lungs or systemically. While immense research has been poured into this disease in an effort to find a therapeutic strategy, the heterogeneously diffuse nature of the disease has not yielded a cure for the disease. Death from this disease is strongly attributed to reduced gas exchange from a severely compromised alveolar-capillary barrier. The only …
The Role Of The Pleckstrin Homology Domain-Containing Protein Ckip-1 In Activation Of P21-Activated Kinase 1 (Pak1),
2015
George Washington University
The Role Of The Pleckstrin Homology Domain-Containing Protein Ckip-1 In Activation Of P21-Activated Kinase 1 (Pak1), Yong-Bae Kim, Yong Jae Shin, Adhiraj Roy, Jeong-Ho Kim
Biochemistry and Molecular Medicine Faculty Publications
Upon growth factor stimulation, PAK1 is recruited to the plasma membrane and activated by a mechanism that requires its phosphorylation at S223 by the protein kinase CK2. However, the upstream signaling molecules that regulate this phosphorylation event are not clearly defined. Here, we demonstrate a major role of the CK2α-interacting protein CKIP-1 in activation of PAK1. CK2α, CKIP-1 and PAK1 are translocated to membrane ruffles in response to the epidermal growth factor (EGF), where CKIP-1 mediates the interaction between CK2α, and PAK1 in a PI3K-dependent manner. Consistently, we observe that PAK1 mediates phosphorylation and modulation of the activity of p41-Arc, …
Targeting Neddylation Induces Dna Damage And Checkpoint Activation And Sensitizes Chronic Lymphocytic Leukemia B Cells To Alkylating Agents,
2015
Oregon Health and Science University
Targeting Neddylation Induces Dna Damage And Checkpoint Activation And Sensitizes Chronic Lymphocytic Leukemia B Cells To Alkylating Agents, C Paiva, J C. Godbersen, A Berger, J R. Brown, A V. Danilov
Dartmouth Scholarship
Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 …
Mechanotransduction: Use The Force(S),
2015
University College London
Mechanotransduction: Use The Force(S), Ewa K. Paluch, Celeste M. Nelson, Nicolas Biais, Ben Fabry, Jens Moeller, Beth L. Pruitt, Carina Wollnik, Galina Kudryasheva, Florian Rehfeldt, Walter Federle
Publications and Research
Mechanotransduction - how cells sense physical forces and translate them into biochemical and biological responses - is a vibrant and rapidly-progressing field, and is important for a broad range of biological phenomena. This forum explores the role of mechanotransduction in a variety of cellular activities and highlights intriguing questions that deserve further attention.
Comparison Of Different Modulators That Affect Macrophage Activation In Vitro,
2015
University of Arkansas, Fayetteville
Comparison Of Different Modulators That Affect Macrophage Activation In Vitro, Alda Alexa Díaz Pérez
Graduate Theses and Dissertations
Inflammation is known as a mechanism to regulate and control infections as well as promote tissue repair. Macrophages (Mф) are known to be a major cell type in the initiation, sustainability and resolution of inflammation. Moreover, Mф are essential for the remodeling process that is also known as the wound healing response. The objective of this research was to compare five modulators (acetylsalicylic acid (ASA), dexamethasone (DEX), prostaglandin E2 (PGE2), iloprost, and resolvin D1 (RvD1) for their anti-inflammatory effects on macrophages in vitro. Then, Mф phenotype in terms of gene expression and secreted cytokine response was determined. Our study compared …
Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors,
2015
University of Maryland - Baltimore
Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg
Pharmacy Faculty Articles and Research
Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …
Characterization Of The Role That Alternative Ribonucleotide Reductases Play In Restoring Replication In The Presence Of Hydroxyurea In Escherichia Coli,
2015
Portland State University
Characterization Of The Role That Alternative Ribonucleotide Reductases Play In Restoring Replication In The Presence Of Hydroxyurea In Escherichia Coli, Michael Sadek
PSU McNair Scholars Online Journal
DNA replication is essential for cells to grow and divide. Ribonucleotide reductase is an essential enzyme that is responsible for the formation of deoxyribonucleotides that are used in DNA synthesis during replication. Hydroxyurea is a chemotherapeutic agent that is thought to work by specifically inhibiting the ribonuceotide reductase to prevent replication. However, recent studies in E. coli have shown that following an initial period of inhibition, DNA synthesis then recovers in the presence of hydroxyurea, suggesting that the mode of death and cellular response to hydroxyurea is more complex than originally proposed. The E.coli genome encodes three ribonucleotide reductases that …
Expression, Localization, And Kinetic Characterization Of The Phospholipid Biosynthesis Enzyme Ctp: Phosphocholine Cytidylyltransferase From The Protozoan Parasite Leishmania Major,
2015
Illinois State University
Expression, Localization, And Kinetic Characterization Of The Phospholipid Biosynthesis Enzyme Ctp: Phosphocholine Cytidylyltransferase From The Protozoan Parasite Leishmania Major, Justin Daniel Theodore Lange
Theses and Dissertations
The eukaryotic parasite Leishmania is the causative agent of the disease leishmaniasis. L. major is the most common of 21 species that causes visceral leishmaniasis in humans, and 30 that cause the same disease in other mammals. Visceral leishmaniasis causes fever, weight loss, and over a short amount of time, multiple organ failure, and has a 100% mortality rate within 2 years. This makes it the second largest parasitic killer in the world behind malaria. Over 90% of the worldâ??s cases of visceral leishmaniasis have been reported in underdeveloped countries of India, Bangladesh, Nepal, Sudan, Ethiopia and Brazil, with 500,000 …
