Chemicals and Drugs Commons^™

No Effect In Plasma Corticosterone Levels After Observation Of Diseased Conspecifics, B. M. Hardy, M. Chang, S. Mccallum, S. Santangelo, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Organisms commonly respond to stressors in their environment by increasing the secretion of corticosterone (CORT). While increased CORT is acknowledged as a response to predation risk by organisms inhabiting a landscape of fear, new research raises the potential for changes in CORT as a response to the risk of infection by organisms in their environment. An increase in CORT of a healthy, uninfected individual in response to their perception of the risk of infection in their environment could change their susceptibility to infection, highlighting a significant role for CORT to alter host–pathogen dynamics. To investigate the effects of infection risk …

Abstract 2587 Recombinant Expression And Purification Of A. Vinelandii Cown In E. Coli, Julie Takei, Cedric P. Owens, Katie Sanders, Neeraja Gajendran

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The goal of this project is to study the protein CowN in the diazotroph Azotobacter vinelandii (Av) in comparison to CowN in Gluconacetobacter diazotrophicus (Gd). Nitrogenase is an enzyme that catalyzes the reduction of nitrogen gas into ammonia in diazotrophic bacteria. In many diazotrophs, the protein CowN prevents nitrogenase inhibition from the environmental gas carbon monoxide (CO). Previous work studied CowN in the diazotroph G. diazotrophicus. In G. diazotrophicus, CowN binds to nitrogenase and weakens CO binding to its active site. The mechanism of CowN has only been investigated in G. diazotrophicus. Thus, we are interested in determining if CowN's …

Abstract 2853 Prmt7 Negatively Regulates The Expression P53 In Response To Dna Damage, Molly Niswender, Lorenzo Pessi, Cecilia Lopez, Marco Bisoffi

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Protein Arginine Methyltransferase 7 (PRMT7) is the only member of the protein arginine methyltransferase protein family that monomethylates its protein substrates. PRMT7 is found in both the nucleus and cytoplasm of breast cells and is believed to play a robust role in the tumorigenesis and metastasis of breast cancer. The goal of this project is to uncover possible pathways for PRMT7 to promote cancer progression. A preliminary antibody array was performed to determine the regulation of known cancer-related proteins by PRMT7. An early-stage human breast cancer cell line, MCF-7, was transfected with plasmid pCDH1-hPRMT7-GFP to over-express PRMT7. Qualitative and quantitative …

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 …

Aars Online: A Collaborative Database On The Structure, Function, And Evolution Of The Aminoacyl-Trna Synthetases, Jordan Douglas, Haissi Cui, John J. Perona, Oscar Vargas-Rodriguez, Henna Tyynismaa, Claudia Alvarez Carreño, Jiqiang Ling, Lluís Ribas De Pouplana, Xiang-Lei Yang, Michael Ibba, Hubert Becker, Frédéric Fischer, Marie Sissler, Charles W. Carter Jr., Peter Wills

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The aminoacyl-tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight in various translational and non-translational activities beyond aminoacylation, and are linked to many genetic disorders. The aaRS have a subtle ontology characterized by structural and functional idiosyncrasies that vary from organism to organism, and protein to protein. Across the tree of life, the 22 coded amino acids are handled by 16 evolutionary families of Class I aaRS and 21 families of Class II aaRS. We introduce AARS Online, an interactive Wikipedia-like …

Stress Granule Formation Helps To Mitigate Neurodegeneration, M. Rebecca Glineburg, Evrim Yildirim, Nicolas Gomez, Genesis Rodriguez, Jaclyn Pak, Xingli Li, Christopher Altheim, Jacob Waksmacki, Gerald M. Mcinerney, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and …

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …

Mutational Analysis Of The Nitrogenase Carbon Monoxide Protective Protein Cown Reveals That A Conserved C‑Terminal Glutamic Acid Residue Is Necessary For Its Activity, Dustin L. Willard, Joshuah J. Arellano, Mitch Underdahl, Terrence M. Lee, Avinash S. Ramaswamy, Gabriella Fumes, Agatha Kliman, Emily Y. Wong, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work …

Purification And Biochemical Characterization Of The Dna Binding Domain Of The Nitrogenase Transcriptional Activator Nifa From Gluconacetobacter Diazotrophicus, Heidi G. Standke, Lois Kim, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

NifA is a σ⁵⁴ activator that turns on bacterial nitrogen fixation under reducing conditions and when fixed cellular nitrogen levels are low. The redox sensing mechanism in NifA is poorly understood. In α- and β-proteobacteria, redox sensing involves two pairs of Cys residues within and immediately following the protein’s central AAA⁺ domain. In this work, we examine if an additional Cys pair that is part of a C(X)5 C motif and located immediately upstream of the DNA binding domain of NifA from the α-proteobacterium Gluconacetobacter diazotrophicus (Gd) is involved in redox sensing. We hypothesize that the …

Α7 Nicotinic Acetylcholine Receptor Interaction With G Proteins In Breast Cancer Cell Proliferation, Motility, And Calcium Signaling, Murat Oz, Justin R. King, Keun-Hang Susan Yang, Sarah Khushaish, Yulia Tchugunova, Maitham A. Khajah, Yunus A. Luqmani, Nadine Kabbani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Chronic smoking is a primary risk factor for breast cancer due to the presence of various toxins and carcinogens within tobacco products. Nicotine is the primary addictive component of tobacco products and has been shown to promote breast cancer cell proliferation and metastases. Nicotine activates nicotinic acetylcholine receptors (nAChRs) that are expressed in cancer cell lines. Here, we examine the role of the α7 nAChR in coupling to heterotrimeric G proteins within breast cancer MCF-7 cells. Pharmacological activation of the α7 nAChR using choline or nicotine was found to increase proliferation, motility, and calcium signaling in MCF-7 cells. This effect …

The Pros Of Changing Trna Identity, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The notion that errors in protein synthesis are universally harmful to the cell has been questioned by findings that suggest such mistakes may sometimes be beneficial. However, how often these beneficial mistakes arise from programmed changes in gene expression as opposed to reduced accuracy of the translation machinery is still unclear. A new study published in JBC shows that some bacteria have beneficially evolved the ability to mistranslate specific parts of the genetic code, a trait that allows improved antibiotic resistance.

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …

Oxidative Stress Strongly Restricts The Effect Of Codon Choice On The Efficiency Of Protein Synthesis In Escherichia Coli, Lorenzo Eugenio Leiva, Sara Elgamal, Sebastian A. Leidel, Omar Orellana, Michael Ibba, Assaf Katz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Introduction

The response of enterobacteria to oxidative stress is usually considered to be regulated by transcription factors such as OxyR and SoxR. Nevertheless, several reports have shown that under oxidative stress the levels, modification and aminoacylation of tRNAs may be altered suggesting a role of codon bias in regulation of gene expression under this condition.

Methods

In order to characterize the effects of oxidative stress on translation elongation we constructed a library of 61 plasmids, each coding for the green fluorescent protein (GFP) translationally fused to a different set of four identical codons.

Results

Using these reporters, we observed that …

Identification And Characterization Of Epicuticular Proteins Of Nematodes Sharing Motifs With Cuticular Proteins Of Arthropods, Bruno Betschart, Marco Bisoffi, Ferial Alaeddine

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Specific collagens and insoluble proteins called cuticlins are major constituents of the nematode cuticles. The epicuticle, which forms the outermost electron-dense layer of the cuticle, is composed of another category of insoluble proteins called epicuticlins. It is distinct from the insoluble cuticlins localized in the cortical layer and the fibrous ribbon underneath lateral alae. Our objective was to identify and characterize genes and their encoded proteins forming the epicuticle. The combination between previously obtained laboratory results and recently made available data through the whole-genome shotgun contigs (WGS) and the transcriptome Shotgun Assembly (TSA) sequencing projects of Ascaris suum allowed us …

Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …

Characterizing The Amino Acid Activation Center Of The Naturally Editing-Deficient Aminoacyl-Trna Synthetase Phers In Mycoplasma Mobile, Nien-Ching Han, Arundhati Kavoor, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

To ensure correct amino acids are incorporated during protein synthesis, aminoacyl-tRNA synthetases (aaRSs) employ proofreading mechanisms collectively referred to as editing. Although editing is important for viability, editing-deficient aaRSs have been identified in host-dependent organisms. In Mycoplasma mobile, editing-deficient PheRS and LeuRS have been identified. We characterized the amino acid activation site of MmPheRS and identified a previously unknown hyperaccurate mutation, L287F. Additionally, we report that m-Tyr, an oxidation byproduct of Phe which is toxic to editing-deficient cells, is poorly discriminated by MmPheRS activation and is not subjected to editing. Furthermore, expressing MmPheRS and the hyperaccurate variants renders …

Human Oncoprotein 5mp Suppresses General And Repeat-Associated Non-Aug Translation Via Eif3 By A Common Mechanism, Chingakham Ranjit Singh, M. Rebecca Glineburg, Chelsea Moore, Naoki Tani, Rahul Jaiswal, Ye Zou, Eric Aube, Sarah Gillaspie, Mackenzie Thornton, Ariana Cecil, Madelyn Hilgers, Azuma Takasu, Izumi Asano, Masayo Asano, Carlos R. Escalante, Akira Nakamura, Peter K. Todd, Katsura Asano

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

eIF5-mimic protein (5MP) is a translational regulatory protein that binds the small ribosomal subunit and modulates its activity. 5MP is proposed to reprogram non-AUG translation rates for oncogenes in cancer, but its role in controlling non-AUG initiated synthesis of deleterious repeat-peptide products, such as FMRpolyG observed in fragile-X-associated tremor ataxia syndrome (FXTAS), is unknown. Here, we show that 5MP can suppress both general and repeat-associated non-AUG (RAN) translation by a common mechanism in a manner dependent on its interaction with eIF3. Essentially, 5MP displaces eIF5 through the eIF3c subunit within the preinitiation complex (PIC), thereby increasing the accuracy of initiation. …

Deacylated Trna Accumulation Is A Trigger For Bacterial Antibiotic Persistence Independent Of The Stringent Response, Whitney N. Wood, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence occurs when bacteria are treated with an antibiotic and the majority of the population rapidly dies off, but a small subpopulation enters into a dormant, persistent state and evades death. Diverse pathways leading to nucleoside triphosphate (NTP) depletion and restricted translation have been implicated in persistence, suggesting alternative redundant routes may exist to initiate persister formation. To investigate the molecular mechanism of one such pathway, functional variants of an essential component of translation (phenylalanyltRNA synthetase [PheRS]) were used to study the effects of quality control on antibiotic persistence. Upon amino acid limitation, elevated PheRS quality control led …

Apigenin And Structurally Related Flavonoids Allosterically Potentiate The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Waheed Shabbir, Keun-Hang Susan Yang, Bassem Sadek, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Phytochemicals, such as monoterpenes, polyphenols, curcuminoids, and flavonoids, are known to have anti-inflammatory, antioxidant, neuroprotective, and procognitive effects. In this study, the effects of several polyhydroxy flavonoids, as derivatives of differently substituted 5,7-dihydroxy-4H-chromen-4-one including apigenin, genistein, luteolin, kaempferol, quercetin, gossypetin, and phloretin with different lipophilicities (cLogP), as well as topological polar surface area (TPSA), were tested for induction of Ca²⁺ transients by α7 human nicotinic acetylcholine (α7 nACh) receptors expressed in SH-EP1 cells. Apigenin (10 μM) caused a significant potentiation of ACh (30 μM)-induced Ca²⁺ transients, but did not affect Ca²⁺ transients induced by high K^{+ …}

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In this study, effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT₃) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by two-electrode voltage clamp method in Xenopus oocytes. The inhibition was time- and concentration-dependent with an IC₅₀ = 62 μM. The effect of capsaicin was not altered in the presence of capsazepine, and by intracellular BAPTA injections or trans-membrane potential changes. In radio-ligand binding studies, capsaicin did not change the specific binding of the 5-HT₃ antagonist [³H]GR65630, indicating that it is a noncompetitive inhibitor of …

Modulation Of Escherichia Coli Translation By The Specific Inactivation Of TrnaGly Under Oxidative Stress, Lorenzo Eugenio Leiva, Andrea Pincheira, Sara Elgamal, Sandra D. Kienast, Verónica Bravo, Johannes Leufken, Daniela Gutiérrez, Sebastian A. Leidel, Michael Ibba, Assaf Katz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial oxidative stress responses are generally controlled by transcription factors that modulate the synthesis of RNAs with the aid of some sRNAs that control the stability, and in some cases the translation, of specific mRNAs. Here, we report that oxidative stress additionally leads to inactivation of tRNA^Gly in Escherichia coli, inducing a series of physiological changes. The observed inactivation of tRNA^Gly correlated with altered efficiency of translation of Gly codons, suggesting a possible mechanism of translational control of gene expression under oxidative stress. Changes in translation also depended on the availability of glycine, revealing a mechanism whereby bacteria …

Translational Regulation Of Environmental Adaptation In Bacteria, Rodney Tollerson Ii, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacteria must rapidly respond to both intracellular and environmental changes to survive. One critical mechanism to rapidly detect and adapt to changes in environmental conditions is control of gene expression at the level of protein synthesis. At each of the three major steps of translation—initiation, elongation, and termination—cells use stimuli to tune translation rate and cellular protein concentrations. For example, changes in nutrient concentrations in the cell can lead to translational responses involving mechanisms such as dynamic folding of riboswitches during translation initiation or the synthesis of alarmones, which drastically alter cell physiology. Moreover, the cell can fine-tune the levels …

Aminoacyl-Trna Synthetases, Miguel Angel Rubio Gomez, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The aminoacyl-tRNA synthetases are an essential and universally distributed family of enzymes that plays a critical role in protein synthesis, pairing tRNAs with their cognate amino acids for decoding mRNAs according to the genetic code. Synthetases help to ensure accurate translation of the genetic code by using both highly accurate cognate substrate recognition and stringent proofreading of noncognate products. While alterations in the quality control mechanisms of synthetases are generally detrimental to cellular viability, recent studies suggest that in some instances such changes facilitate adaption to stress conditions. Beyond their central role in translation, synthetases are also emerging as key …

Targeting Trna-Synthetase Interactions Towards Novel Therapeutic Discovery Against Eukaryotic Pathogens, Paul Kelly, Fatemeh Hadi-Nezhad, Dennis Y. Liu, Travis J. Lawrence, Roger G. Linington, Michael Ibba, David H. Ardell

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and independently in eight distinct clades of trypanosomes, identifying parasite-specific informative features, …

A Native Function For Ran Translation And Cgg Repeats In Regulating Fragile X Protein Synthesis, Caitlin M. Rodriguez, Shannon E. Wright, Michael G. Kearse, Jill M. Haenfler, Brittany N. Flores, Yu Liu, Marius F. Ifrim, M. Rebecca Glineburg, Amy Krans, Paymaan Jafar-Nejad, Michael A. Sutton, Gary J. Bassell, Jack M. Parent, Frank Rigo, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Repeat-associated non-AUG-initiated translation of expanded CGG repeats (CGG RAN) from the FMR1 5′-leader produces toxic proteins that contribute to neurodegeneration in fragile X-associated tremor/ataxia syndrome. Here we describe how unexpanded CGG repeats and their translation play conserved roles in regulating fragile X protein (FMRP) synthesis. In neurons, CGG RAN acts as an inhibitory upstream open reading frame to suppress basal FMRP production. Activation of mGluR5 receptors enhances FMRP synthesis. This enhancement requires both the CGG repeat and CGG RAN initiation sites. Using non-cleaving antisense oligonucleotides (ASOs), we selectively blocked CGG RAN. This ASO blockade enhanced endogenous FMRP expression in human …

Prostate Field Cancerization And Exosomes: Association Between Cd9, Early Growth Response 1 And Fatty Acid Synthase, Farideh Amirrad, Philip A. Pytak, Neda Sadeghiani-Pelar, Julie P. T. Nguyen, Emily L. Cauble, Anna C. Jones

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Intracapsular and well‑defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre‑malignancy. Such alterations in histologically normal tumor‑adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR‑1) and the lipogenic enzyme fatty acid synthase …

Immune-Endocrine Links To Gregariousness In Wild House Mice, Patricia C. Lopes, Esther H. D. Carlitz, Morgan Kindel, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Social interactions are critically important for survival and impact overall-health, but also impose costs on animals, such as exposure to contagious agents. The immune system can play a critical role in modulating social behavior when animals are sick, as has been demonstrated within the context of “sickness behaviors.” Can immune molecules affect or be affected by social interactions even when animals are not sick, therefore serving a role in mediating pathogen exposure? We tested whether markers of immune function in both the blood and the brain are associated with gregariousness, quantified as number of animals interacted with per day. To …

Alanyl-Trna Synthetase Quality Control Prevents Global Dysregulation Of The Escherichia Coli Proteome, Paul Kelly, Nicholas Backes, Kyle Mohler, Christopher Buser, Arundhati Kavoor, Jesse Rinehart, Gregory Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mechanisms have evolved to prevent errors in replication, transcription, and translation of genetic material, with translational errors occurring most frequently. Errors in protein synthesis can occur at two steps, during tRNA aminoacylation and ribosome decoding. Recent advances in protein mass spectrometry have indicated that previous reports of translational errors have potentially underestimated the frequency of these events, but also that the majority of translational errors occur during ribosomal decoding, suggesting that aminoacylation errors are evolutionarily less tolerated. Despite that interpretation, there is evidence that some aminoacylation errors may be regulated, and thus provide a benefit to the cell, while others …

The Fitness Landscape Of The African Salmonella Typhimurium St313 Strain D23580 Reveals Unique Properties Of The Pbt1 Plasmid, Rocío Canals, Roy R. Chaudhuri, Rebecca E. Steiner, Siân V. Owen, Natalia Quinones-Olvera, Melita A. Gordon, Michael Baym, Michael Ibba, Jay C. D. Hinton

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We have used a transposon insertion sequencing (TIS) approach to establish the fitness landscape of the African Salmonella enterica serovar Typhimurium ST313 strain D23580, to complement our previous comparative genomic and functional transcriptomic studies. We used a genome-wide transposon library with insertions every 10 nucleotides to identify genes required for survival and growth in vitro and during infection of murine macrophages. The analysis revealed genomic regions important for fitness under two in vitro growth conditions. Overall, 724 coding genes were required for optimal growth in LB medium, and 851 coding genes were required for growth in SPI-2-inducing minimal medium. These …