Medicine and Health Sciences Commons^™

The 11s Proteasomal Activator Regγ Impacts Polyglutamine-Expanded Androgen Receptor Aggregation And Motor Neuron Viability Through Distinct Mechanisms., Jill M. Yersak, Heather L. Montie, Erica S. Chevalier-Larsen, Yuhong Liu, Lan Huang, Martin Rechsteiner, Diane E. Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is caused by expression of a polyglutamine (polyQ)-expanded androgen receptor (AR). The inefficient nuclear proteasomal degradation of the mutant AR results in the formation of nuclear inclusions containing amino-terminal fragments of the mutant AR. PA28γ (also referred to as REGγ) is a nuclear 11S-proteasomal activator with limited proteasome activation capabilities compared to its cytoplasmic 11S (PA28α, PA28β) counterparts. To clarify the role of REGγ in polyQ-expanded AR metabolism, we carried out genetic and biochemical studies in cell models of SBMA. Overexpression of REGγ in a PC12 cell model of SBMA increased polyQ-expanded AR aggregation …

Tumor Necrosis Factor Inhibitors In Psoriatic Arthritis., Santhi Mantravadi, Alexis Ogdie, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory disease that can result in significant disability. With the emergence of tumor necrosis factor inhibitors (TNFi), therapeutic outcomes in PsA have improved substantially. The clinical efficacy and the inhibition of radiographic progression demonstrated by TNFi have transformed the management of PsA. However, there is still an unmet need for a subset of patients who do not respond adequately to TNFi. Areas covered: This review provides an overview of the pharmacokinetics of TNFi, the efficacy of TNFi in PsA, and the role of immunogenicity of TNFi in the treatment of PsA. In addition, …

Yamat-Seq: An Efficient Method For High-Throughput Sequencing Of Mature Transfer Rnas., Megumi Shigematsu, Shozo Honda, Phillipe Loher, Aristeidis G. Telonis, Isidore Rigoutsos, Yohei Kirino

Computational Medicine Center Faculty Papers

Besides translation, transfer RNAs (tRNAs) play many non-canonical roles in various biological pathways and exhibit highly variable expression profiles. To unravel the emerging complexities of tRNA biology and molecular mechanisms underlying them, an efficient tRNA sequencing method is required. However, the rigid structure of tRNA has been presenting a challenge to the development of such methods. We report the development of Y-shaped Adapter-ligated MAture TRNA sequencing (YAMAT-seq), an efficient and convenient method for high-throughput sequencing of mature tRNAs. YAMAT-seq circumvents the issue of inefficient adapter ligation, a characteristic of conventional RNA sequencing methods for mature tRNAs, by employing the efficient …

Identification Of Octopaminergic Neurons That Modulate Sleep Suppression By Male Sex Drive., Daniel R. Machado, Dinis Afonso, Alexandra R. Kenny, Arzu Öztürk-Çolak, Emilia H. Moscato, Benjamin Mainwaring, Matthew Kayser, Kyunghee Koh

Department of Neuroscience Faculty Papers

Molecular and circuit mechanisms for balancing competing drives are not well understood. While circadian and homeostatic mechanisms generally ensure sufficient sleep at night, other pressing needs can overcome sleep drive. Here, we demonstrate that the balance between sleep and sex drives determines whether male flies sleep or court, and identify a subset of octopaminergic neurons (MS1) that regulate sleep specifically in males. When MS1 neurons are activated, isolated males sleep less, and when MS1 neurons are silenced, the normal male sleep suppression in female presence is attenuated and mating behavior is impaired. MS1 neurons do not express the sexually dimorphic …

Effect Of Oral Iron Repletion On Exercise Capacity In Patients With Heart Failure With Reduced Ejection Fraction And Iron Deficiency: The Ironout Hf Randomized Clinical Trial., Gregory D Lewis, Rajeev Malhotra, Adrian F Hernandez, Steven E Mcnulty, Andrew Smith, G Michael Felker, W H Wilson Tang, Shane J Larue, Margaret M Redfield, Marc J Semigran, Michael M Givertz, Peter Van Buren, David J Whellan, Kevin J Anstrom, Monica R Shah, Patrice Desvigne-Nickens, Javed Butler, Eugene Braunwald

Department of Medicine Faculty Papers

Importance: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown.

Objective: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency.

Design, Setting, and Participants: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF (

Interventions: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. …

Laboratory Tests In Patients Treated With Isotretinoin: Occurrence Of Liver And Muscle Abnormalities And Failure Of Ast And Alt To Predict Liver Abnormality., Guy F. Webster, Timothy G. Webster, Lorraine R. Grimes

Department of Dermatology and Cutaneous Biology Faculty Papers

Current laboratory monitoring may not be optimal. A retrospective chart review was performed on thelaboratory results of 246 patients who were treated with isotretinoin for acne over a 9-year period. Tests obtained were CBC, lipid panel, AST, ALT, CK, GGT,and C-reactive protein. Thirty-five patients had an elevated AST and 35 of these had an elevated CK; 32 had an elevated ALT and 11 of these had an elevated CK. Thirteen patients had an elevated GGT; in 5 this was the only abnormality, whereas 8 had a GGT elevation accompanied by an elevated AST or ALT. Two had an elevated GGT …

Download Entire Issue: Collaborative Healthcare: Interprofessional Practice, Education And Evaluation (Jcipe), Volume 8, Number 1, 2017

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

Download Entire Issue: Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE), Volume 8, Number 1, 2017

Near Miss Root Cause Analysis Reflection, Alicia Muratore

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

As a medical student, my education has largely been divided into two different schools of teaching: didactic classroom instruction and hands-on apprenticeship. The balance between these two components has shifted towards the latter as I have progressed in my education. For example, we first learn about the anatomy and physiology of the heart, then progress to learn about the textbook presentation and patho-physiology as well as treatments of processes such as congestive heart failure. Then as upper years we encounter patients who are faced with these conditions and are tasked with using our knowledge base to provide appropriate care and …

Impact Of An Interprofessional Leadership Program On Collaboration In Practice, Julie Vincent, Dnp, Rn, Cenp, Diane Andrews, Phd, Rn, Lt. General (Ret.) Mark Hertling, Sandra Galura, Phd, Rn, Loretta Forlaw, Phd, Rn

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

Purpose

The purpose of this project was to improve attitudes towards collaboration between nurse and physician leaders and to describe the changes in attitudes and behaviors following completion of an interprofessional education (IPE) leadership development program.

Significance

The Institute of Medicine (IOM) 1999 study, To Err is Human: Building a Safer Health System, demonstrated that poor collaboration among clinicians can contribute to negative patient outcomes and further outlined that traditional methods of learning in healthcare result in nurses and physicians becoming isolated from one another and thus unprepared to work collaboratively (Delunas & Rouse, 2014). The nurse-physician (RN-MD) …

Enhancing Services To Homeless Populations Through An Interprofessional Virtual World Simulation, Susan Toth-Cohen, Anne C. Smith, M.Ed.

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

Simulations are increasingly implemented as core teaching strategies in healthcare education. Along with the growth and proliferation of many forms of simulation, new venues for implementation also have emerged, including virtual world (VW) role play simulations (Jarmon, Traphagan, Mayrath, & Trevedi, 2009; Rogers, 2010; Walker & Rockinson-Szapkiw, 2009). These VW simulations enable interprofessional teams of students to learn and test their knowledge and skills in real time, within settings that can model a wide range of institutional and community practice environments.

VW simulations provide many of the same benefits that have been described in campus-based simulations, such as practice within …

Caregiver Evaluation Of A Palliative Care Consultation Team Using The Jefferson Teamwork Observation Guide (Jtog) By Caregivers Of Severely Ill Patients, John Liantonio, Md, Beth Wagner, Crnp, Kristine Swartz Md, Molly Hanson, Crnp, Kathleen Mechler, Md, Brooke Worster, Md, Carol Brown, Susan Parks Md

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

Background:

Palliative care teams strive to improve the quality of life of patients and their families who are faced with life threatening illnesses by addressing the physical, psychosocial and spiritual aspects of their care (World HealthOrganization, 2017). The palliative care team is an interprofessional team made up of physicians, nurses, social workers and chaplains and often partners with many other disciplines. Palliative care has been shown to increase quality of life in patients with cancer and help improve communication amongst patients, their families and their care teams (Temel, 2010; Seow, 2008). Additionally, many studies have sought to prove the effectiveness …

From The Editors

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

This spring marks an exciting time for JCIPE as we prepare to celebrate our 10^th anniversary as a center for interprofessional education. Ten years ago, students across our six colleges rarely interacted; IPE was a fairly new and often misunderstood term on campus. Now, a decade later, Jefferson has embraced a culture where IPE and collaborative practice are expected, welcomed and increasingly integrated across the learning continuum, from first year students to seasoned providers. This spring, we graduated our ninth cohort of Jefferson Health Mentors Program students, developed three new advanced IPE electives, compiled a comprehensive inventory of IPE …

Evidence-Based Treatment Options In Recurrent And/Or Metastatic Squamous Cell Carcinoma Of The Head And Neck., Athanassios Argiris, Kevin J. Harrington, Makoto Tahara, Jeltje Schulten, Pauline Chomette, Ana Ferreira Castro, Lisa Licitra

Department of Medical Oncology Faculty Papers

The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy (CT), followed by maintenance cetuximab (the "EXTREME" regimen). This regimen is supported by a phase 3 randomized trial and subsequent observational studies, and it confers well-documented survival benefits, with median survival ranging between approximately 10 and 14 months, overall response rates between 36 and 44%, and disease control rates of over 80%. Furthermore, as indicated by patient-reported outcome measures, the addition of cetuximab …

The Nephrotoxicity Of Vancomycin., Edward J. Filippone, Walter K. Kraft, John L. Farber

Department of Medicine Faculty Papers

No abstract provided.

Treatment-Related Decisional Conflict, Quality Of Life, And Comorbid Illness In Older Adults With Cancer, Jeannette Kates, Phd, Msn, Gnp-Bc

College of Nursing Posters

As the aging population in the nation increases, cancer diagnoses in this age group will also increase. The many chronic medical conditions associated with older adults are confounded by a diagnosis of cancer. Older adults with cancer are at risk for physical, psychological, and functional decline as a result of not only the cancer, but also the cancer treatment. In their current research agenda, the Oncology Nursing Society identified the need for research related to multiple comorbidities in older adults with cancer. This study utilized a cross-sectional, descriptive, correlational study design to explore the relationships between and among treatment-related decisional …

Guanylate Cyclase C As A Target For Prevention, Detection, And Therapy In Colorectal Cancer., Allison A. Aka, Jeff A. Rappaport, Amanda M. Pattison, Takami Sato, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

INTRODUCTION: Colorectal cancer remains the second leading cause of cancer death in the United States, and new strategies to prevent, detect, and treat the disease are needed. The receptor, guanylate cyclase C (GUCY2C), a tumor suppressor expressed by the intestinal epithelium, has emerged as a promising target. Areas covered: This review outlines the role of GUCY2C in tumorigenesis, and steps to translate GUCY2C-targeting schemes to the clinic. Endogenous GUCY2C-activating ligands disappear early in tumorigenesis, silencing its signaling axis and enabling transformation. Pre-clinical models support GUCY2C ligand supplementation as a novel disease prevention paradigm. With the recent FDA approval of the …

Buprenorphine For The Treatment Of The Neonatal Abstinence Syndrome., Walter K. Kraft, Susan C. Adeniyi-Jones, Inna Chervoneva, Jay S. Greenspan, Diane J. Abatemarco, Karol Kaltenbach, Michelle E. Ehrlich

Department of Obstetrics and Gynecology Faculty Papers

Background: Current pharmacologic treatment of the neonatal abstinence syndrome with morphine is associated with a lengthy duration of therapy and hospitalization. Buprenorphine may be more effective than morphine for this indication. Methods: In this single-site, double-blind, double-dummy clinical trial, we randomly assigned 63 term infants (≥37 weeks of gestation) who had been exposed to opioids in utero and who had signs of the neonatal abstinence syndrome to receive either sublingual buprenorphine or oral morphine. Infants with symptoms that were not controlled with the maximum dose of opioid were treated with adjunctive phenobarbital. The primary end point was the duration of …

A Word From The Writing Center (May 2017), Jennifer Wilson, Ms, Els

A Word From the Writing Team (Newsletter)

This issue includes:

• Grammar writing tip on ZOMBIE nouns!
• Keep Reading with BrowZine

Role Of Differentially Expressed Microrna-139-5p In The Regulation Of Phenotypic Internal Anal Sphincter Smooth Muscle Tone., Jagmohan Singh, Ipsita Mohanty, Sankar Addya, Benjamin Philllips, Hwan Mee Yong, Steven S. An, Raymond B. Penn, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

The present study focused on the role of microRNA-139-5p (miRNA-139-5p) in the regulation of basal tone in internal anal sphincter (IAS). Applying genome-wide miRNA microarrays on the phenotypically distinct smooth muscle cells (SMCs) within the rat anorectrum, we identified miRNA-139-5p as differentially expressed RNA repressor with highest expression in the purely phasic smooth muscle of anococcygeus (ASM) vs. the truly tonic smooth muscle of IAS. This pattern of miRNA-139-5p expression, previously shown to target ROCK2, was validated by target prediction using ingenuity pathway (IPA) and by qPCR analyses. Immunoblotting, immunocytochemistry (ICC), and functional assays using IAS tissues and cells subjected …

A Description Of The Methods Of The Aspirin Supplementation For Pregnancy Indicated Risk Reduction In Nulliparas (Aspirin) Study., Matthew K. Hoffman, Shivaprasad S. Goudar, Bhalachandra S. Kodkany, Norman Goco, Marion Koso-Thomas, Menachem Miodovnik, Elizabeth M Mcclure, Dennis D. Wallace, Jennifer J. Hemingway-Foday, Antoinette Tshefu, Adrien Lokangaka, Carl L. Bose, Elwyn Chomba, Musaku Mwenechanya, Waldemar A. Carlo, Ana Garces, Nancy F. Krebs, K. Michael Hambidge, Sarah Saleem, Robert L. Goldenberg, Archana Patel, Patricia L. Hibberd, Fabian Esamai, Edward A. Liechty, Robert Silver, Richard J. Derman

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Preterm birth (PTB) remains the leading cause of neonatal mortality and long term disability throughout the world. Though complex in its origins, a growing body of evidence suggests that first trimester administration of low dose aspirin (LDA) may substantially reduce the rate of PTB.

METHODS: Hypothesis: LDA initiated in the first trimester reduces the risk of preterm birth. Study Design Type: Prospective randomized, placebo-controlled, double-blinded multi-national clinical trial conducted in seven low and middle income countries. Trial will be individually randomized with one-to-one ratio (intervention/control) Population: Nulliparous women between the ages of 14 and 40, with a singleton pregnancy …

Identification Of A Functional Genetic Variant Driving Racially Dimorphic Platelet Gene Expression Of The Thrombin Receptor Regulator, Pctp., Xianguo Kong, Lukas M. Simon, Michael Holinstat, Chad A. Shaw, Paul F. Bray, Leonard C. Edelstein

Cardeza Foundation for Hematologic Research

Platelet activation in response to stimulation of the Protease Activated Receptor 4 (PAR4) receptor differs by race. One factor that contributes to this difference is the expression level of Phosphatidylcholine Transfer Protein (PCTP), a regulator of platelet PAR4 function. We have conducted an expression Quantitative Trait Locus (eQTL) analysis that identifies single nucleotide polymorphisms (SNPs) linked to the expression level of platelet genes. This analysis revealed 26 SNPs associated with the expression level of PCTP at genome-wide significance (p < 5×10(-8)). Using annotation from ENCODE and other public data we prioritised one of these SNPs, rs2912553, for functional testing. The allelic frequency of rs2912553 is racially-dimorphic, in concordance with the racially differential expression of PCTP. Reporter gene assays confirmed that the single nucleotide change caused by rs2912553 altered the transcriptional potency of the surrounding genomic locus. Electromobility shift assays, luciferase assays, and overexpression studies indicated a role for the megakaryocytic transcription factor GATA1. In summary, we have integrated multi-omic data to identify and functionalise an eQTL. This, along with the previously described relationship between PCTP and PAR4 function, allows us to characterise a genotype-phenotype relationship through the mechanism of gene expression.

Chlamydia Hijacks Arf Gtpases To Coordinate Microtubule Posttranslational Modifications And Golgi Complex Positioning., Jordan Wesolowski, Mary M. Weber, Agata Nawrotek, Cheryl A. Dooley, Mike Calderon, Claudette M. St Croix, Ted Hackstadt, Jacqueline Cherfils, Fabienne Paumet

Department of Microbiology and Immunology Faculty Papers

The intracellular bacterium Chlamydia trachomatis develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both …

Creating A New Education Paradigm To Prepare Nurses For The 21st Century, Mary Bouchaud, Denise Brown, Beth Ann Swan

College of Nursing Faculty Papers & Presentations

Nurse educators are accountable to keep baccalaureate education responsive to the ever changing healthcare delivery environment. The changing context of healthcare delivery requires focusing on population health and social determinants, providing interprofessional, team-based care, advancing innovation, and preparing practice ready baccalaureate nursing graduates. To be practice ready, nursing graduates must be agile and think and reason on their feet due to increasing care complexity beyond the hospital walls, changing care needs of individuals and families, advancing technology, shifting settings of care delivery, and managing multiple transitions. The purpose of this paper is to consider these healthcare changes and share a …

Conference Posters Archived In The Jefferson Digital Commons, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

The Jefferson Digital Commons has archived over 680 conference posters. Here are some of the most recent additions to the collection:

• Evaluating Value-Based Frameworks Used for Relapsed or Refractory Multiple Myeloma Regimens: ICER Report, ASCO Value Framework, and NCCN Evidence Blocks
• Looking Beyond the Traditional: Integrating a New Curriculum Design into an Immersion Practicum Evaluation Tool
• Infection Prevention and Control in Baccalaureate Nursing Education: Identifying Content, Teaching Strategies and Gaps
• Book Club at Intern Orientation to Help Frame Professional Identity

And many more posters!

Sigma1 Targeting To Suppress Aberrant Androgen Receptor Signaling In Prostate Cancer., Jeffrey D. Thomas, Charles G. Longen, Halley M. Oyer, Nan Chen, Christina M. Maher, Joseph M. Salvino, Blase Kania, Kelsey N. Anderson, William F. Ostrander, Karen E. Knudsen, Felix J. Kim

Department of Cancer Biology Faculty Papers

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that …

Quality Assurance Guidelines For Superficial Hyperthermia Clinical Trials : Ii. Technical Requirements For Heating Devices., Hana Dobšíček Trefná, Johannes Crezee, Manfred Schmidt, Dietmar Marder, Ulf Lamprecht, Michael Ehmann, Jacek Nadobny, Josefin Hartmann, Nicolleta Lomax, Sultan Abdel-Rahman, Sergio Curto, Akke Bakker, Mark D. Hurwitz, Chris J. Diederich, Paul R. Stauffer, Gerard C. Van Rhoon

Department of Radiation Oncology Faculty Papers

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this …

Nobody Really Knows How To Perform Endoscopic Necrosectomy., Douglas G. Adler, Ali A. Siddiqui

Division of Gastroenterology and Hepatology Faculty Papers

No abstract provided.

Substance Use, Treatment, And Demographic Characteristics Of Pregnant Women Entering Treatment For Opioid Use Disorder Differ By United States Census Region., Dennis J Hand, Vanessa L Short, Diane J Abatemarco

Department of Obstetrics and Gynecology Faculty Papers

Opioid use disorder (OUD) among pregnant women increased substantially between 1992 and 2012 across the United States, with the greatest increases occurring in the southern states. We analyzed the 2013 Treatment Episodes Database-Admissions to determine how substances used, characteristics of treatment, and demographics of pregnant women entering treatment for opioid use disorder vary between geographical regions. Analyses were restricted to cases where women reported being pregnant at the time of admission and reported opioids as the primary substance problem leading to the treatment admission. Characteristics were compared between U.S. census regions using Chi-square tests and logistic regression with the South …

Sonoelastography Of The Common Flexor Tendon Of The Elbow With Histologic Agreement: A Cadaveric Study., Andrea S Klauser, Mathias J Pamminger, Ethan J. Halpern, Mohamed M H Abd Ellah, Bernhard Moriggl, Mihra S Taljanovic, Christian Deml, Judith Sztankay, Guenter Klima, Leonhard Gruber, Werner R Jaschke

Department of Radiology Faculty Papers

Purpose To determine the correlation of the results of conventional B-mode ultrasonography (US) and compression sonoelastography with histologic results in common flexor tendons of the elbow in human cadavers. Materials and Methods Twenty-five common flexor tendons were evaluated in 16 fresh, unembalmed cadavers of 11 women with a median age of 85 years (range, 71-101 years) and five men with a median age of 78 years (range, 70-88 years). Informed consent was provided according to the last will of the donors. B-mode US results were classified as grade 1, normal tendon with homogeneous fibrillar pattern; grade 2, tendon thickening or …

Chemical And Structural Characterization Of A Model Post-Termination Complex (Potc) For The Ribosome Recycling Reaction: Evidence For The Release Of The Mrna By Rrf And Ef-G., Nobuhiro Iwakura, Takeshi Yokoyama, Fabio Quaglia, Kaoru Mitsuoka, Kazuhiro Mio, Hideki Shigematsu, Mikako Shirouzu, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

A model Post-Termination Complex (PoTC) used for the discovery of Ribosome Recycling Factor (RRF) was purified and characterized by cryo-electron microscopic analysis and biochemical methods. We established that the model PoTC has mostly one tRNA, at the P/E or P/P position, together with one mRNA. The structural studies were supported by the biochemical measurement of bound tRNA and mRNA. Using this substrate, we establish that the release of tRNA, release of mRNA and splitting of ribosomal subunits occur during the recycling reaction. Order of these events is tRNA release first followed by mRNA release and splitting almost simultaneously. Moreover, we …