Elongation Factor-P At The Crossroads Of The Host-Endosymbiont Interface,
2015
The Ohio State University
Elongation Factor-P At The Crossroads Of The Host-Endosymbiont Interface, Andrei Rajkovic, Anne Witzky, William Navarre, Andrew J. Darwin, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Elongation factor P (EF-P) is an ancient bacterial translational factor that aids the ribosome in polymerizing oligo-prolines. EF-P structurally resembles tRNA and binds in-between the exit and peptidyl sites of the ribosome to accelerate the intrinsically slow reaction of peptidyl-prolyl bond formation. Recent studies have identified in separate organisms, two evolutionarily convergent EF-P post-translational modification systems (EPMS), split predominantly between gammaproteobacteria, and betaproteobacteria. In both cases EF-P receives a post-translational modification, critical for its function, on a highly conserved residue that protrudes into the peptidyl-transfer center of the ribosome. EPMSs are comprised of a gene(s) that synthesizes the precursor molecule …
Tnf-Α-Induced Micrornas Control Dystrophin Expression In Becker Muscular Dystrophy.,
2015
George Washington University
Tnf-Α-Induced Micrornas Control Dystrophin Expression In Becker Muscular Dystrophy., Alyson A. Fiorillo, Christopher R. Heier, James S. Novak, Christopher B. Tully, Kristy J. Brown, Kitipong Uaesoontrachoon, Maria C. Vila, Peter P. Ngheim, Luca Bello, Joe N. Kornegay, Corrado Angelini, Terence A. Partridge, Kanneboyina Nagaraju, Eric P. Hoffman
Genomics and Precision Medicine Faculty Publications
The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45–47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low …
Acidic And Basic Destruction Of Tissues,
2015
Indiana State University
Acidic And Basic Destruction Of Tissues, Cydney Eaton
University Honors Program
A coroner’s case I had learned about involved a man attempting to dispose of a body with acid. Shortly after exposure, the man was apprehended and the body was located. Upon investigation, police force determined the acid used to be hydrochloric acid, however, exact concentration remains unknown (Kohr, 2010). This led to the question of which easily accessible acid works best to degrade tissue. To answer this, an experiment was conducted involving pig feet and various concentrations of common acids and a single strong base. The feet were submerged in the solutions overnight and mass percent lost or gained was …
Electrochemical Characterization Of Protein Adsorption Onto Yngrt-Au And Vlgxe-Au Surfaces,
2015
Oakland University
Electrochemical Characterization Of Protein Adsorption Onto Yngrt-Au And Vlgxe-Au Surfaces, Hanna Trzeciakiewicz, Jose Esteves-Villanueva, Rania Soudy, Kamaljit Kaur, Sanela Martic-Milne
Pharmacy Faculty Articles and Research
The adsorption of the proteins CD13, mucin and bovine serum albumin on VLGXE-Au and YNGRT-Au interfaces was monitored by electrochemical impedance spectroscopy in the presence of [Fe(CN)6]3−/4−. The hydrophobicity of the Au surface was tailored using specific peptides, blocking agents and diluents. The combination of blocking agents (ethanolamine or n-butylamine) and diluents (hexanethiol or 2-mercaptoethanol) was used to prepare various peptide-modified Au surfaces. Protein adsorption onto the peptide-Au surfaces modified with the combination of n-butylamine and hexanethiol produced a dramatic decrease in the charge transfer resistance, Rct, for all three proteins. In contrast, polar peptide-surfaces induced a minimal change in …
Molecular Overlap In The Regulation Of Sk Channels By Small Molecules And Phosphoinositides,
2015
Chapman University
Molecular Overlap In The Regulation Of Sk Channels By Small Molecules And Phosphoinositides, Miao Zhang, Xuan-Yu Meng, Ji-Fang Zhang, Meng Cui, Diomedes E. Logothetis
Pharmacy Faculty Articles and Research
Phosphatidylinositol 4,5-bisphosphate (PIP2) directly interacts with the small-conductance Ca2+-activated K+ 2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP2 binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP2 to potentiate channel activity. This novel modulation of PIP2 sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP2-dependent proteins.
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 …
Molecular Determinants Underlying Binding Specificities Of The Abl Kinase Inhibitors: Combining Alanine Scanning Of Binding Hot Spots With Network Analysis Of Residue Interactions And Coevolution,
2015
Chapman University
Molecular Determinants Underlying Binding Specificities Of The Abl Kinase Inhibitors: Combining Alanine Scanning Of Binding Hot Spots With Network Analysis Of Residue Interactions And Coevolution, Amanda Tse, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown …
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 …
Cyclic Rhamnosylated Elongation Factor P Establishes Antibiotic Resistance In Pseudomonas Aeruginosa,
2015
The Ohio State University
Cyclic Rhamnosylated Elongation Factor P Establishes Antibiotic Resistance In Pseudomonas Aeruginosa, Andrei Rajkovic, Sarah Erickson, Anne Witzky, Owen E. Branson, Jin Seo, Philip R. Gafken, Michael A. Frietas, Julian P. Whitelegge, Kym F. Faull, William Wiley Navarre, Andrew J. Darwin, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Elongation factor P (EF-P) is a ubiquitous bacterial protein that is required for the synthesis of poly-proline motifs during translation. In Escherichia coli and Salmonella enterica, the posttranslational β-lysylation of Lys34 by the PoxA protein is critical for EF-P activity. PoxA is absent from many bacterial species such as Pseudomonas aeruginosa, prompting a search for alternative EF-P posttranslation modification pathways. Structural analyses of P. aeruginosa EF-P revealed the attachment of a single cyclic rhamnose moiety to an Arg residue at a position equivalent to that at which β-Lys is attached to E. coli EF-P. Analysis of the genomes …
Orexin Receptor Activation Generates Gamma Band Input To Cholinergic And Serotonergic Arousal System Neurons And Drives An Intrinsic Ca(2+)-Dependent Resonance In Ldt And Ppt Cholinergic Neurons,
2015
New York Medical College
Orexin Receptor Activation Generates Gamma Band Input To Cholinergic And Serotonergic Arousal System Neurons And Drives An Intrinsic Ca(2+)-Dependent Resonance In Ldt And Ppt Cholinergic Neurons, Masaru Ishibashi, Iryna Gumenchuk, Bryan Kang, Catherine Steger, Elizabeth Lynn, Nancy Molina, Leonard M. Eisenberg, Christopher S. Leonard
NYMC Faculty Publications
A hallmark of the waking state is a shift in EEG power to higher frequencies with epochs of synchronized intracortical gamma activity (30-60 Hz) - a process associated with high-level cognitive functions. The ascending arousal system, including cholinergic laterodorsal (LDT) and pedunculopontine (PPT) tegmental neurons and serotonergic dorsal raphe (DR) neurons, promotes this state. Recently, this system has been proposed as a gamma wave generator, in part, because some neurons produce high-threshold, Ca(2+)-dependent oscillations at gamma frequencies. However, it is not known whether arousal-related inputs to these neurons generate such oscillations, or whether such oscillations are ever transmitted to neuronal …
Synthesis And Characterization Of A New Peptide Prodrug Of Glucosamine With Enhanced Gut Permeability,
2015
University of Alberta
Synthesis And Characterization Of A New Peptide Prodrug Of Glucosamine With Enhanced Gut Permeability, Hamed Gilzad Kohan, Kamaljit Kaur, Fakhreddin Jamali
Pharmacy Faculty Articles and Research
The aim of this study was to synthesize a peptide prodrug of glucosamine (GlcN) with increased gut permeability through the gut peptide transporter 1 (PepT1). Glycine-Valine ester derivative of GlcN (GVG) was synthesised using solid phase synthesis followed by characterization and evaluation of its physicochemical and intestinal stability. In addition, GVG was evaluated for its ability to be biotransformed to GlcN in the liver homogenate. In vitro absorption of the new prodrug through everted rat gut was also assessed. GVG demonstrated significant and meaningful increased gut permeability as compared with GlcN. It showed favorable stability in the gut and a …
Characterization Of Ghrelin O-Acyltransferase Active Site,
2015
Syracuse University
Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton
Renée Crown University Honors Thesis Projects - All
Ghrelin, first discovered in 1999, is a 28-amino acid peptide hormone involved in the regulation of appetite, insulin secretion and sensitivity, and many neurological effects such as learning, memory, and depression.1-6 Ghrelin has been identified to have a unique posttranslational octanoylation carried out by the enzyme ghrelin O-acyltransferase (GOAT). This distinctive modification is a point of interest in studying GOAT whereby blocking the acylation of the ghrelin could potentially halt the activity of the peptide hormone and provide a means of treating obesity, diabetes, and other diseases affected by ghrelin levels. The duration of my project involved working …
Accidental Phosphine Gas Poisoning With Fatal Myocardial Dysfunction In Two Families,
2015
Aga Khan University
Accidental Phosphine Gas Poisoning With Fatal Myocardial Dysfunction In Two Families, Saleem Akhtar, Arshalooz Rehman, Surraya Bano, Anwarul Haque
Department of Emergency Medicine
ABSTRACT Aluminum phosphide is commonly used as a rodenticide and insecticide and is one of the most fatal poisons. The active ingredient is Phosphine gas which inhibits cytochrome oxidase and cellular oxygen utilization. The clinical symptoms are due to multiorgan involvement including cardiac toxicity which is the most common cause of mortality. Severity of clinical manifestations depends upon the amount of the gas to which a person is exposed. There is no specific antidote available. High index of suspicion and early aggressive treatment is the key to success. We report 2 cases of aluminum phosphide toxicity in 2 families due …
Targeting Cell Cycle Proteins In Breast Cancer Cells With Sirna By Using Lipid-Substituted Polyethylenimines,
2015
University of Alberta
Targeting Cell Cycle Proteins In Breast Cancer Cells With Sirna By Using Lipid-Substituted Polyethylenimines, Manoj Parmar, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Robert Maranchuk, Judith C. Hugh, Hasan Uludag
Pharmacy Faculty Articles and Research
The cell cycle proteins are key regulators of cell cycle progression whose de-regulation is one of the causes of breast cancer. RNA interference (RNAi) is an endogenous mechanism to regulate gene expression and it could serve as the basis of regulating aberrant proteins including cell cycle proteins. Since the delivery of small interfering RNA (siRNA) is a main barrier for implementation of RNAi therapy, we explored the potential of a non-viral delivery system, 2.0 kDa polyethylenimines substituted with linoleic acid and caprylic acid, for this purpose. Using a library of siRNAs against cell cycle proteins, we identified cell division cycle …
A-803467, A Tetrodotoxin-Resistant Sodium Channel Blocker, Modulates Abcg2-Mediated Mdr In Vitro And In Vivo,
2015
Touro College of Pharmacy
A-803467, A Tetrodotoxin-Resistant Sodium Channel Blocker, Modulates Abcg2-Mediated Mdr In Vitro And In Vivo, Nagaraju Anreddy, Atish Patel, Yun-Kai Zhang, Yi-Jun Wang, Suneet Shukla, Rishil J. Kathawala, Priyank Kumar
Touro College of Pharmacy (New York) Publications and Research
ATP-binding cassette subfamily G member 2 (ABCG2) is a member of the ABC transporter superfamily proteins, which has been implicated in the development of multidrug resistance (MDR) in cancer, apart from its physiological role to remove toxic substances out of the cells. The diverse range of substrates of ABCG2 includes many antineoplastic agents such as topotecan, doxorubicin and mitoxantrone. ABCG2 expression has been reported to be significantly increased in some solid tumors and hematologic malignancies, correlated to poor clinical outcomes. In addition, ABCG2 expression is a distinguishing feature of cancer stem cells, whereby this membrane transporter facilitates resistance to the …
Possible Effects Of Nanosecond Pulsed Electric Fields On Proteins,
2015
Old Dominion University
Possible Effects Of Nanosecond Pulsed Electric Fields On Proteins, Stephen J. Beebe
Bioelectrics Publications
No abstract provided.
Elucidation Of A Novel Pathway In Staphylococcus Aureus: The Essential Site-Specific Processing Of Ribosomal Protein L27,
2015
Virginia Commonwealth University
Elucidation Of A Novel Pathway In Staphylococcus Aureus: The Essential Site-Specific Processing Of Ribosomal Protein L27, Erin A. Wall
Theses and Dissertations
Ribosomal protein L27 is a component of the eubacterial large ribosomal subunit that has been shown to play a critical role in substrate stabilization during protein synthesis. This function is mediated by the L27 N-terminus, which protrudes into the peptidyl transferase center where it interacts with both A-site and P-site tRNAs as well as with 23S rRNA. We observed that L27 in S. aureus and other Firmicutes is encoded with a short N-terminal extension that is not present in most Gram-negative organisms, and is absent from mature ribosomes. The extension contains a conserved cleavage motif; nine N-terminal amino acids are …
Design, Synthesis, Antiviral Activity, And Pre-Formulation Development Of Poly-Larginine- Fatty Acyl Derivatives Of Nucleoside Reverse Transcriptase Inhibitors,
2015
University of Rhode Island
Design, Synthesis, Antiviral Activity, And Pre-Formulation Development Of Poly-Larginine- Fatty Acyl Derivatives Of Nucleoside Reverse Transcriptase Inhibitors, Bhanu P. Pemmaraju, Swapnil Malekar, Hitesh K. Agarwal, Rakesh Tiwari, Donghoon Oh, Gustavo F. Doncel, David R. Worthen, Keykavous Parang
Pharmacy Faculty Articles and Research
The objective of this work was to design conjugates of anti-HIV nucleosides conjugated with fatty acids and cell-penetrating poly-L-arginine (polyArg) peptides. Three conjugates of polyArg cell-penetrating peptides with fatty acyl derivatives of alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC) were synthesized. In general, the compounds exhibited anti-HIV activity against X4 and R5 cell-free virus with EC50 values of 1.5–16.6 μM. FLT-CO-(CH2)12-CO-(Arg)7 exhibited EC50 values of 2.9 μM and 3.1 μM against X4 and R5 cell-free virus, respectively. The FLT conjugate was selected for further preformulation studies by determination of solution state degradation and lipid solubility. The compound was found to …
Regulation Of Ghrelin: A Possible Treatment Option For Obesity And Diabetes,
2015
Touro College
Regulation Of Ghrelin: A Possible Treatment Option For Obesity And Diabetes, Sarah Picciotto
The Science Journal of the Lander College of Arts and Sciences
Obesity is a mounting problem in America today. One major concern about obesity is that it is a risk factor for type 2 diabetes, a disease that impairs insulin sensitivity and secretion. This interferes with blood glucose levels and can cause hyperglycemia, which is when there is too much circulating glucose in the blood. Ghrelin, an amino acid peptide responsible for appetite stimulation and energy balance, plays a direct role in insulin secretion and glucose metabolism. In many experiments, elevated ghrelin levels are associated with decreased insulin secretion from pancreatic islet cells. Although ghrelin concentration is decreased in obese individuals …
Mechanisms, Potential Therapies, And The Role Of Tgf-Β In The Formation Of Scars,
2015
Touro College
Mechanisms, Potential Therapies, And The Role Of Tgf-Β In The Formation Of Scars, Isaac Traube
The Science Journal of the Lander College of Arts and Sciences
Scarring is the inevitable outcome of wound healing. This review looks at some of the underlying mechanisms of this complex process with the aim of identifying targets for therapeutic manipulation that could result in reduced scarring or even scarless wound repair. Fetal wounds are shown to heal without scars primarily due to low levels of TGF-β1 and TGF-β2 and high levels of TGF-β3 as compared to adult wounds which heal with scars. Abnormal excessive scarring in keloid and hypertrophic scars are also attributed to TGF-β. Clinical manipulation of TGF-β ratios showed promise as a therapeutic means of controlling scar formation. …
