Piwi Is Required To Limit Exhaustion Of Aging Somatic Stem Cells,
2017
Touro University California
Piwi Is Required To Limit Exhaustion Of Aging Somatic Stem Cells, Pedro Sousa-Victor, Arshad Ayyaz, Rippei Hayashi, Yanyan Qi, David T. Madden, Victoria V. Lunyak, Heinrich Jasper
Faculty Publications & Research of the TUC College of Pharmacy
Please see the graphical abstract in the supplemental files.
Discovering A Novel Antifungal Target In Downstream Sterol Biosynthesis Using A Squalene Synthase Functional Motif,
2017
University of Kentucky
Discovering A Novel Antifungal Target In Downstream Sterol Biosynthesis Using A Squalene Synthase Functional Motif, Kristin Brooke Linscott
Theses and Dissertations--Molecular and Cellular Biochemistry
The sterol biosynthetic pathway is essential for growth of all eukaryotic cells and the main target of antifungal agents. The emergence of resistance to these antifungals in an already ill patient population indicates a need to develop drugs that have a broad spectrum of activity among pathogenic fungi and have minimal patient toxicity. Squalene synthase is the first committed step in the sterol pathway and has been studied intensively for development of antifungal agents. While the overall architecture of this enzyme is identical throughout eukaryotes, it was shown that plant and animal genes cannot complement a squalene synthase knockout mutation …
Taurine's Effect On Cocaine Reward And Neurogenesis In The Adolescent Male Rat Brain.,
2017
CUNY City College
Taurine's Effect On Cocaine Reward And Neurogenesis In The Adolescent Male Rat Brain., Avery E. Villa-Gonzalez
Dissertations and Theses
Adolescence is a developmentally critical transition from childhood to adulthood including both maturation of the body and the brain. Neuroplastic changes result in dynamic organization of the brain during adolescence, leaving them vulnerable to development of mental illness and drug-seeking behavior. According to the United Nations Office on Drugs and Crime, the psychostimulant cocaine is the second most popular illicit drug in the world. Cocaine, amongst having many detrimental effects, has shown to also decrease hippocampal neurogenesis, resulting in decreased neuroplasticity and cognitive dysfunction. Previous students in our laboratory have shown that treatment of adult male rats with the essential …
Molecular Modeling Of Novel Tryptamine Analogs With Antibiotic Potential Through Their Inhibition Of Tryptophan Synthase,
2017
Claremont McKenna College
Molecular Modeling Of Novel Tryptamine Analogs With Antibiotic Potential Through Their Inhibition Of Tryptophan Synthase, Jared Schattenkerk
CMC Senior Theses
The growing prevalence of antibiotic-resistant bacteria is a global health crisis that threatens the effectiveness of antibiotics in medical treatment. Increases in the number of antibiotic-resistant bacteria and a drop in the pharmaceutical development of novel antibiotics have combined to form a situation that is rapidly increasing the likelihood of a post-antibiotic era. The development of antibiotics with novel enzymatic targets is critical to stall this growing crisis. In silico methods of molecular modeling and drug design were utilized in the development of novel tryptamine analogs as potential antibiotics through their inhibition of the bacterial enzyme tryptophan synthase. Following the …
Structure-Function Investigation Of Proteins Involved In Cellulose Biosynthesis By Escherichia Coli,
2017
Wilfrid Laurier University
Structure-Function Investigation Of Proteins Involved In Cellulose Biosynthesis By Escherichia Coli, Thomas Brenner
Theses and Dissertations (Comprehensive)
Bacteria thrive within multicellular communities called biofilms consisting of a self-produced matrix. Biofilm matrices improve bacterial adherence to surfaces while creating a barrier from host immune responses, disinfectants, antibiotics and other environmental factors. Persistent colonization by the widely distributed pathogens, Escherichia coli and Salmonella spp., has been linked to production of biofilms composed of the exopolysaccharide cellulose. Cellulose-containing biofilms are also important to Acetobacter, Sarcina, Rhizobium and Agrobacterium species to form symbiotic and pathogenic interactions. In Enterobacteriaceae, two operons (bcsABZC and bcsEFG) are proposed to encode for proteins that form a cellulose biosynthetic complex that spans the …
Chemical Probes For Protein Α-N-Terminal Methylation,
2017
Virginia Commonwealth University
Chemical Probes For Protein Α-N-Terminal Methylation, Brianna D. Mackie
Theses and Dissertations
While protein α-N-terminal methylation has been known for nearly four decades since it was first uncovered on bacteria ribosomal proteins L33, the function of this modification is still not entirely understood. Recent discoveries have demonstrated α-N-terminal methylation is essential to stabilize the interactions between regulator of chromosome condensation 1 (RCC1) and chromatin during mitosis, to localize and enhance the interaction of centromere proteins (CENPs) with chromatin, and to facilitate the recruitment of DNA damage-binding protein 2 (DDB2) to DNA damage foci. Identification of N-terminal methyltransferase 1 (NTMT1) unveiled the eukaryotic methylation writer for protein α-N-termini. In addition, NTMT2 that shares …
Il-15 Activates The Jak3/Stat3 Signaling Pathway To Mediate Glucose Uptake In Skeletal Muscle Cells,
2016
Chapman University
Il-15 Activates The Jak3/Stat3 Signaling Pathway To Mediate Glucose Uptake In Skeletal Muscle Cells, James E. Krolopp, Shantaé M. Thornton, Marcia J. Abbott
Health Sciences and Kinesiology Faculty Articles
Myokines are specialized cytokines that are secreted from skeletal muscle (SKM) in response to metabolic stimuli, such as exercise. Interleukin-15 (IL-15) is a myokine with potential to reduce obesity and increase lean mass through induction of metabolic processes. It has been previously shown that IL-15 acts to increase glucose uptake in SKM cells. However, the downstream signals orchestrating the link between IL-15 signaling and glucose uptake have not been fully explored. Here we employed the mouse SKM C2C12 cell line to examine potential downstream targets of IL-15-induced alterations in glucose uptake. Following differentiation, C2C12 cells were treated overnight with 100 …
Synthesis Of Rhamnosylated Arginine Glycopeptides And Determination Of The Glycosidic Linkage In Bacterial Elongation Factor P,
2016
University of Sydney
Synthesis Of Rhamnosylated Arginine Glycopeptides And Determination Of The Glycosidic Linkage In Bacterial Elongation Factor P, Siyao Wang, Leo Corcilius, Phillip B. Sharp, Andrei Rajkovic, Michael Ibba, Benjamin L. Parker, Richard J. Payne
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
A new class of N-linked protein glycosylation – arginine rhamnosylation – has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid “cassettes” that can be directly installed into rhamnosylated peptides. Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies.
Hnrnpa2 Is A Novel Histone Acetyltransferase That Mediates Mitochondrial Stress-Induced Nuclear Gene Expression,
2016
University of Pennsylvania
Hnrnpa2 Is A Novel Histone Acetyltransferase That Mediates Mitochondrial Stress-Induced Nuclear Gene Expression, Manti Guha, Satish Srinivasan, Kip Guja, Edison Mejia, Miguel Garcia-Diaz, F. Brad Johnson, Gordon Ruthel, Brett A. Kaufman, Eric F. Rappaport, M. Rebecca Glineburg, Ji-Kang Fang, Andres J. Klein-Szanto, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2). These processes are reversed when mitochondrial DNA content is restored to near normal cell levels. We show that the mitochondrial stress-induced …
Partial Amino Acid Sequence Of Lipid Transfer Protein From Fennel (Foeniculum Vulgare) Seeds,
2016
Chapman University
Partial Amino Acid Sequence Of Lipid Transfer Protein From Fennel (Foeniculum Vulgare) Seeds, Hasan Al-Shiyab, Caroline Aziz
Student Scholar Symposium Abstracts and Posters
Fennel (Foeniculum vulgare) is a biennial Egyptian medicinal plant with an aromatic odor that belongs to the family Apiaceae (Umbelliferae). Fennel seeds are commonly used in traditional medicine, as they are known to have anti-inflammatory, anti-fungal and anti-cancerous activities. The major constituents of the fennel plant are sugars, minerals, essential fatty acids, proteins and fibers. Although, there are numerous studies on the medicinal properties of essential oils of the fennel seeds, but there is limited data reported on the proteins and peptides. The aims of this project are to fully characterize the primary structure of proteins and to determine their …
The Complex Evolutionary History Of Aminoacyl-Trna Synthetases,
2016
University of Thessaly
The Complex Evolutionary History Of Aminoacyl-Trna Synthetases, Anargyros Chaliotis, Panayotis Vlastaridis, Dimitris Mossialos, Michael Ibba, Hubert D. Becker, Constantinos Stathopoulos, Grigorios D. Amoutzias
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Aminoacyl-tRNA synthetases (AARSs) are a superfamily of enzymes responsible for the faithful translation of the genetic code and have lately become a prominent target for synthetic biologists. Our large-scale analysis of >2500 prokaryotic genomes reveals the complex evolutionary history of these enzymes and their paralogs, in which horizontal gene transfer played an important role. These results show that a widespread belief in the evolutionary stability of this superfamily is misconceived. Although AlaRS, GlyRS, LeuRS, IleRS, ValRS are the most stable members of the family, GluRS, LysRS and CysRS often have paralogs, whereas AsnRS, GlnRS, PylRS and SepRS are often absent …
Exploring Molecular Mechanisms Of Paradoxical Activation In The Braf Kinase Dimers: Atomistic Simulations Of Conformational Dynamics And Modeling Of Allosteric Communication Networks And Signaling Pathways,
2016
Chapman University
Exploring Molecular Mechanisms Of Paradoxical Activation In The Braf Kinase Dimers: Atomistic Simulations Of Conformational Dynamics And Modeling Of Allosteric Communication Networks And Signaling Pathways, Amanda Tse, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
The recent studies have revealed that most BRAF inhibitors can paradoxically induce kinase activation by promoting dimerization and enzyme transactivation. Despite rapidly growing number of structural and functional studies about the BRAF dimer complexes, the molecular basis of paradoxical activation phenomenon is poorly understood and remains largely hypothetical. In this work, we have explored the relationships between inhibitor binding, protein dynamics and allosteric signaling in the BRAF dimers using a network-centric approach. Using this theoretical framework, we have combined molecular dynamics simulations with coevolutionary analysis and modeling of the residue interaction networks to determine molecular determinants of paradoxical activation. We …
Isoacceptor Specific Characterization Of Trna Aminoacylation And Misacylation In Vivo,
2016
The Ohio State University
Isoacceptor Specific Characterization Of Trna Aminoacylation And Misacylation In Vivo, Kyle Mohler, Rebecca Mann, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Amino acid misincorporation during protein synthesis occurs due to misacylation of tRNAs or defects in decoding at the ribosome. While misincorporation of amino acids has been observed in a variety of contexts, less work has been done to directly assess the extent to which specific tRNAs are misacylated in vivo, and the identity of the misacylated amino acid moiety. Here we describe tRNA isoacceptor specific aminoacylation profiling (ISAP), a method to identify and quantify the amino acids attached to a tRNA species in vivo. ISAP allows compilation of aminoacylation profiles for specific isoacceptors tRNAs. To demonstrate the efficacy and …
Maintenance Of Transcription-Translation Coupling By Elongation Factor P,
2016
The Ohio State University
Maintenance Of Transcription-Translation Coupling By Elongation Factor P, Sara Elgamal, Irina Artsimovitch, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Under conditions of tight coupling between translation and transcription, the ribosome enables synthesis of full-length mRNAs by preventing both formation of intrinsic terminator hairpins and loading of the transcription termination factor Rho. While previous studies have focused on transcription factors, we investigated the role of Escherichia coli elongation factor P (EF-P), an elongation factor required for efficient translation of mRNAs containing consecutive proline codons, in maintaining coupled translation and transcription. In the absence of EF-P, the presence of Rho utilization (rut) sites led to an ~30-fold decrease in translation of polyproline-encoding mRNAs. Coexpression of the Rho inhibitor Psu …
Novel Ph-Sensitive Cyclic Peptides,
2016
University of Rhode Island
Novel Ph-Sensitive Cyclic Peptides, Dhammika Weerakkody, Anna Moshnikova, Naglaa Salem El-Sayed, Ramona-Cosima Adochite, Gregory Slaybaugh, Jovana Golijanin, Rakesh Tiwari, Oleg A. Andreev, Keykavous Parang, Yana K. Reshetnyak
Pharmacy Faculty Articles and Research
A series of cyclic peptides containing a number of tryptophan (W) and glutamic acid (E) residues were synthesized and evaluated as pH-sensitive agents for targeting of acidic tissue and pH-dependent cytoplasmic delivery of molecules. Biophysical studies revealed the molecular mechanism of peptides action and localization within the lipid bilayer of the membrane at high and low pHs. The symmetric, c[(WE)4WC], and asymmetric, c[E4W5C], cyclic peptides translocated amanitin, a polar cargo molecule of similar size, across the lipid bilayer and induced cell death in a pH- and concentration-dependent manner. Fluorescently-labelled peptides were evaluated for targeting of acidic 4T1 mammary tumors in …
Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics,
2016
Purdue University
Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, Matthew L. Capek, Ross Verheul, David H. Thompson
The Summer Undergraduate Research Fellowship (SURF) Symposium
The development of novel and efficient mixing methods is important for optimizing the efficiency of many biological and chemical processes. Tuning the physical and performance properties of nucleic acid-based nanoparticles is one such example known to be strongly affected by mixing efficiency. The characteristics of DNA nanoparticles (such as size, polydispersity, ζ-potential, and gel shift) are important to ensure their therapeutic potency, and new methods to optimize these characteristics are of significant importance to achieve the highest efficacy. In the present study, a simple segmented flow microfluidics system has been developed to augment mixing of pDNA/bPEI nanoparticles. This DNA and …
Expanding The Phenotype Associated With Naa10-Related N-Terminal Acetylation Deficiency.,
2016
George Washington University
Expanding The Phenotype Associated With Naa10-Related N-Terminal Acetylation Deficiency., Chloé Saunier, Svein Isungset Støve, Bernt Popp, Bénédicte Gérard, Marina Blenski, Nicholas Ahmew, +Several Additional Authors
Pediatrics Faculty Publications
N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ …
Structure And Functions Of Angiotensinogen,
2016
University of Kentucky
Structure And Functions Of Angiotensinogen, Hong Lu, Lisa A. Cassis, Craig W. Vander Kooi, Alan Daugherty
Saha Cardiovascular Research Center Faculty Publications
Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides. Although AGT is generally considered as a passive substrate of the renin–angiotensin system, there is accumulating evidence that the regulation and functions of AGT are intricate. Understanding the diversity of AGT properties has been enhanced by protein structural analysis and animal studies. In addition to whole-body genetic deletion, AGT can be regulated in vivo by cell-specific procedures, adeno-associated viral approaches and antisense oligonucleotides. Indeed, the availability of these multiple manipulations of AGT in vivo has provided new insights into the multifaceted roles of AGT. In this review, the combination of …
Translation Control Of Swarming Proficiency In Bacillus Subtilis By 5-Amino-Pentanolylated Elongation Factor P,
2016
The Ohio State University
Translation Control Of Swarming Proficiency In Bacillus Subtilis By 5-Amino-Pentanolylated Elongation Factor P, Andrei Rajkovic, Katherine R. Hummels, Anne Witzky, Sarah Erickson, Philip R. Gafken, Julian P. Whitelegge, Kym F. Faull, Daniel B. Kearns, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Elongation factor P (EF-P) accelerates diprolyl synthesis and requires a posttranslational modification to maintain proteostasis. Two phylogenetically distinct EF-P modification pathways have been described and are encoded in the majority of Gram-negative bacteria, but neither is present in Gram-positive bacteria. Prior work suggested that the EF-P-encoding gene (efp) primarily supports Bacillus subtilis swarming differentiation, whereas EF-P in Gram-negative bacteria has a more global housekeeping role, prompting our investigation to determine whether EF-P is modified and how it impacts gene expression in motile cells. We identified a 5-aminopentanol moiety attached to Lys32 of B. subtilis EF-P that is …
Multiple Quality Control Pathways Limit Non-Protein Amino Acid Use By Yeast Cytoplasmic Phenylalanyl-Trna Synthetase,
2016
The Ohio State University
Multiple Quality Control Pathways Limit Non-Protein Amino Acid Use By Yeast Cytoplasmic Phenylalanyl-Trna Synthetase, Adil Moghal, Lin Hwang, Kym F. Faull, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Non-protein amino acids, particularly isomers of the proteinogenic amino acids, present a threat to proteome integrity if they are mistakenly inserted into proteins. Quality control during aminoacyl-tRNA synthesis reduces non-protein amino acid incorporation by both substrate discrimination and proofreading. For example phenylalanyl-tRNA synthetase (PheRS) proofreads the non-protein hydroxylated phenylalanine derivative m-Tyr after its attachment to tRNAPhe. We now show in Saccharomyces cerevisiae that PheRS misacylation of tRNAPhe with the more abundant Phe oxidation product o-Tyr is limited by kinetic discrimination against o-Tyr-AMP in the transfer step followed by o-Tyr-AMP release from the synthetic …
