Digital Commons Network^™

New Insights And Enhanced Human Norovirus Cultivation In Human Intestinal Enteroids, Khalil Ettayebi, Victoria R Tenge, Nicolas W Cortes-Penfield, Sue E Crawford, Frederick H Neill, Xi-Lei Zeng, Xiaomin Yu, B Vijayalakshmi Ayyar, Douglas Burrin, Sasirekha Ramani, Robert L Atmar, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of epidemic and sporadic acute gastroenteritis worldwide. We previously demonstrated human intestinal stem cell-derived enteroids (HIEs) support cultivation of several HuNoV strains. However, HIEs did not support virus replication from every HuNoV-positive stool sample, which led us to test and optimize new medium conditions, identify characteristics of stool samples that allow replication, and evaluate consistency of replication over time. Optimization of our HIE-HuNoV culture system has shown the following: (i) a new HIE culture medium made with conditioned medium from a single cell line and commercial media promotes robust replication of HuNoV strains …

Macrophage-Engineered Vesicles For Therapeutic Delivery And Bidirectional Reprogramming Of Immune Cell Polarization, Khaga R. Neupane, J. Robert Mccorkle, Timothy J. Kopper, Jourdan E. Lakes, Surya P. Aryal, Masud Abdullah, Aaron A. Snell, John C. Gensel, Jill M. Kolesar, Christopher I. Richards

Spinal Cord and Brain Injury Research Center Faculty Publications

Macrophages, one of the most important phagocytic cells of the immune system, are highly plastic and are known to exhibit diverse roles under different pathological conditions. The ability to repolarize macrophages from pro-inflammatory (M1) to anti-inflammatory (M2) or vice versa offers a promising therapeutic approach for treating various diseases such as traumatic injury and cancer. Herein, it is demonstrated that macrophage-engineered vesicles (MEVs) generated by disruption of macrophage cellular membranes can be used as nanocarriers capable of reprogramming macrophages and microglia toward either pro- or anti-inflammatory phenotypes. MEVs can be produced at high yields and easily loaded with diagnostic molecules …

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction In Tauopathy, Shon A. Koren, Matthew J. Hamm, Ryan Cloyd, Sarah N. Fontaine, Emad Chishti, Chiara Lanzillotta, Jennifer Rodriguez-Rivera, Alexandria Ingram, Michelle Bell, Sara M. Galvis-Escobar, Nicholas Zulia, Fabio Di Domenico, Duc Duong, Nicholas T. Seyfried, David K. Powell, Moriel Vandsburger, Tal Frolinger, Anika M. S. Hartz, John Koren Iii, Jeffrey M. Axten, Nicholas J. Laping, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging …

Manganese Exposure In Juvenile C57bl/6 Mice Increases Glial Inflammatory Responses In The Substantia Nigra Following Infection With H1n1 Influenza Virus., Collin M Bantle, C Tenley French, Jason E Cummings, Shankar Sadasivan, Kevin Tran, Richard A Slayden, Richard Jay Smeyne, Ronald B Tjalkens

Farber Institute for Neuroscience Faculty Papers

Infection with Influenza A virus can lead to the development of encephalitis and subsequent neurological deficits ranging from headaches to neurodegeneration. Post-encephalitic parkinsonism has been reported in surviving patients of H1N1 infections, but not all cases of encephalitic H1N1 infection present with these neurological symptoms, suggesting that interactions with an environmental neurotoxin could promote more severe neurological damage. The heavy metal, manganese (Mn), is a potential interacting factor with H1N1 because excessive exposure early in life can induce long-lasting effects on neurological function through inflammatory activation of glial cells. In the current study, we used a two-hit model of neurotoxin-pathogen …

Induction Of Brain Tumors By The Archetype Strain Of Human Neurotropic Jcpyv In A Transgenic Mouse Model, Luis Del Valle, Kamel Khalili

School of Medicine Faculty Publications

JC Virus (JCPyV), a member of the Polyomaviridiæ family, is a human neurotropic virus with world-wide distribution. JCPyV is the established opportunistic infectious agent of progressive multifocal leukoencephalopathy, a fatal demyelinating disease, which results from the cytolytic infection of oligodendrocytes. Mutations in the regulatory region of JCPyV determine the different viral strains. Mad-1 the strain associated with PML contains two 98 base pair repeats, whereas the archetype strain (CY), which is the transmissible form of JCPyV, contains only one 98 tandem with two insertions of 62 and 23 base pairs respectively. The oncogenicity of JCPyV has been suspected since direct …

Age And Sex Differences In Load-Induced Tibial Cortical Bone Surface Strain Maps, Alessandra Carriero, Behzad Javaheri, Neda Bassir Kazeruni, Andrew A. Pitsillides, Sandra J. Shefelbine

Publications and Research

Bone adapts its architecture to the applied load; however, it is still unclear how bone mechano-adaptation is coordinated and why potential for adaptation adjusts during the life course. Previous animal models have suggested strain as the mechanical stimulus for bone adaptation, but yet it is unknown how mouse cortical bone load-related strains vary with age and sex. In this study, full-field strain maps (at 1 N increments up to 12 N) on the bone surface were measured in young, adult, and old (aged 10, 22 weeks, and 20 months, respectively), male and female C57BL/6J mice with load applied using a …

The Effect Of Alcalase Concentration On The Proteins From The Shells Of Litopenaeus Setiferus (White Shrimp), Liam T. Quan

Journal of the South Carolina Academy of Science

Chitin is a naturally abundant polymer that also happens to be biodegradable. Chitin can be used in a variety of different products such as biodegradable plastics, papers, medical products, foods, and medical treatments. To extract chitin, shells must be demineralized and deproteinized. The goal of this experiment was to examine the effect of the protease Alcalase in the deproteinization of litopenaeus setiferus shells. The hypothesis was that if the concentration of Alcalase increased, then the absorbance of proteins in the spectrophotometer reading would increase. The null hypothesis was that if the concentration increased there would be no change in absorption. …

Clinical Performance Of The Point-Of-Care Cobas Liat For Detection Of Sars-Cov-2 In 20 Minutes: A Multicenter Study., Glen Hansen, Jamie Marino, Zi-Xuan Wang, Kathleen G Beavis, John Rodrigo, Kylie Labog, Lars F Westblade, Run Jin, Nedra Love, Karen Ding, Sachin Garg, Alan Huang, Joanna Sickler, Nam K Tran

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Highly accurate testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the point of care (POC) is an unmet diagnostic need in emergency care and time-sensitive outpatient care settings. Reverse transcription-PCR (RT-PCR) technology is the gold standard for SARS-CoV-2 diagnostics. We performed a multisite U.S. study comparing the clinical performance of the first U.S. Food and Drug Administration (FDA)-authorized POC RT-PCR for detection of SARS-CoV-2 in 20 min, the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test, to the most widely used RT-PCR laboratory test, the cobas 68/8800 SARS-CoV-2 test. Clinical nasopharyngeal swab specimens from 444 patients with …

Spliceosome-Targeted Therapies Trigger An Antiviral Immune Response In Triple-Negative Breast Cancer, Elizabeth A Bowling, Jarey H Wang, Fade Gong, William Wu, Nicholas J Neill, Ik Sun Kim, Siddhartha Tyagi, Mayra Orellana, Sarah J Kurley, Rocio Dominguez-Vidaña, Hsiang-Ching Chung, Tiffany Y-T Hsu, Julien Dubrulle, Alexander B Saltzman, Heyuan Li, Jitendra K Meena, Gino M Canlas, Srinivas Chamakuri, Swarnima Singh, Lukas M Simon, Calla M Olson, Lacey E Dobrolecki, Michael T Lewis, Bing Zhang, Ido Golding, Jeffrey M Rosen, Damian W Young, Anna Malovannaya, Fabio Stossi, George Miles, Matthew J Ellis, Lihua Yu, Silvia Buonamici, Charles Y Lin, Kristen L Karlin, Xiang H-F Zhang, Thomas F Westbrook

Faculty, Staff and Students Publications

Many oncogenic insults deregulate RNA splicing, often leading to hypersensitivity of tumors to spliceosome-targeted therapies (STTs). However, the mechanisms by which STTs selectively kill cancers remain largely unknown. Herein, we discover that mis-spliced RNA itself is a molecular trigger for tumor killing through viral mimicry. In MYC-driven triple-negative breast cancer, STTs cause widespread cytoplasmic accumulation of mis-spliced mRNAs, many of which form double-stranded structures. Double-stranded RNA (dsRNA)-binding proteins recognize these endogenous dsRNAs, triggering antiviral signaling and extrinsic apoptosis. In immune-competent models of breast cancer, STTs cause tumor cell-intrinsic antiviral signaling, downstream adaptive immune signaling, and tumor cell death. Furthermore, RNA …

Assessing Intervals Of Epigallocatechin Gallate (Egcg) And Cannabidiol (Cbd) On Saccharomyces Cerevisiae Cell Reproduction As A Possible Application On Cancer Cell Proliferation, Spandana Anchoori

Journal of the South Carolina Academy of Science

No abstract provided.

Genetic Approach To Elucidate The Role Of Cyclophilin D In Traumatic Brain Injury Pathology, Ryan D. Readnower, W. Brad Hubbard, Olivia J. Kalimon, James W. Geddes, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Cyclophilin D (CypD) has been shown to play a critical role in mitochondrial permeability transition pore (mPTP) opening and the subsequent cell death cascade. Studies consistently demonstrate that mitochondrial dysfunction, including mitochondrial calcium overload and mPTP opening, is essential to the pathobiology of cell death after a traumatic brain injury (TBI). CypD inhibitors, such as cyclosporin A (CsA) or NIM811, administered following TBI, are neuroprotective and quell neurological deficits. However, some pharmacological inhibitors of CypD have multiple biological targets and, as such, do not directly implicate a role for CypD in arbitrating cell death after TBI. Here, we reviewed the …

The Association Of Circulating Amylin With Β-Amyloid In Familial Alzheimer's Disease, Han Gia Ly, Nirmal Verma, Savita Sharma, Deepak Kotiya, Sanda Despa, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Donna M. Wilcock, Larry B. Goldstein, Rita Guerreiro, José Brás, Angela J. Hanson, Suzanne Craft, Andrew J. Murray, Geert Jan Biessels, Claire Troakes, Henrik Zetterberg, John Hardy, Tammaryn Lashley, Alzheimer’S Disease Exome Sequencing Group, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Introduction

This study assessed the hypothesis that circulating human amylin (amyloid‐forming) cross‐seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).

Methods

Evidence of amylin‐AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non‐APP/PS1 rats.

Results

Amylin‐Aβ cross‐seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected …

Distinct Mechanisms Control Genome Recognition By P53 At Its Target Genes Linked To Different Cell Fates., Marina Farkas, Hideharu Hashimoto, Yingtao Bi, Ramana V Davuluri, Lois Resnick-Silverman, James J. Manfredi, Erik W. Debler, Steven B. Mcmahon

Department of Biochemistry and Molecular Biology Faculty Papers

The tumor suppressor p53 integrates stress response pathways by selectively engaging one of several potential transcriptomes, thereby triggering cell fate decisions (e.g., cell cycle arrest, apoptosis). Foundational to this process is the binding of tetrameric p53 to 20-bp response elements (REs) in the genome (RRRCWWGYYYN_0-13RRRCWWGYYY). In general, REs at cell cycle arrest targets (e.g. p21) are of higher affinity than those at apoptosis targets (e.g., BAX). However, the RE sequence code underlying selectivity remains undeciphered. Here, we identify molecular mechanisms mediating p53 binding to high- and low-affinity REs by showing that key determinants of the code are embedded …

A Peek Inside The Machines Of Bacterial Nucleotide Excision Repair, Thanyalak Kraithong, Silas Hartley, David Jeruzalmi, Danaya Pakotiprapha

Publications and Research

Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). …

Week Of January 19, 2021, New York Medical College

InTouch

• NYMC Welcomes Ronald Matten, M.P.A., Associate Vice President of Facilities Management and Capital Planning
• Ninth Symposium Presents the Latest Information on COVID-19
• Chancellor Halperin Shares his Thoughts on the Notion of Public Health Malpractice

Houston Hurricane Harvey Health (Houston-3h) Study: Assessment Of Allergic Symptoms And Stress After Hurricane Harvey Flooding, Abiodun O Oluyomi, Kristen Panthagani, Jesus Sotelo, Xiangjun Gu, Georgina Armstrong, Dan Na Luo, Kristi L Hoffman, Diana Rohlman, Lane Tidwell, Winifred J Hamilton, Elaine Symanski, Kimberly Anderson, Joseph F Petrosino, Cheryl Lyn Walker, Melissa Bondy

Faculty, Staff and Students Publications

BACKGROUND: In August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey's landfall.

METHODS: The Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 …

A High Affinity, Partial Antagonist Effect Of 3,4-Diaminopyridine Mediates Action Potential Broadening And Enhancement Of Transmitter Release At Nmjs, Kristine S Ojala, Scott P Ginebaugh, Man Wu, Evan W Miller, Gloria Ortiz, Manuel Covarrubias, Stephen D Meriney

Department of Neuroscience Faculty Papers

3,4-Diaminopyridine (3,4-DAP) increases transmitter release from neuromuscular junctions (NMJs), and low doses of 3,4-DAP (estimated to reach ∼1 μM in serum) are the Food and Drug Administration (FDA)-Approved treatment for neuro muscular weakness caused by Lambert-Eaton myasthenic syn drome. Canonically, 3,4-DAP is thought to block voltage-gated potassium (Kv) channels, resulting in prolongation of the pre synaptic action potential (AP). However, recent reports have shown that low millimolar concentrations of 3,4-DAP have an off-Target agonist effect on the Cav1 subtype ("L-Type") of voltage-gated calcium (Cav) channels and have speculated that this agonist effect might contribute to 3,4-DAP effects on transmitter release …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

High-Density Lipoproteins And Serum Amyloid A (Saa), Nancy R. Webb

Pharmacology and Nutritional Sciences Faculty Publications

PURPOSE OF REVIEW: Serum amyloid A (SAA) is a highly sensitive acute phase reactant that has been linked to a number of chronic inflammatory diseases. During a systemic inflammatory response, liver-derived SAA is primarily found on high-density lipoprotein (HDL). The purpose of this review is to discuss recent literature addressing the pathophysiological functions of SAA and the significance of its association with HDL.

RECENT FINDINGS: Studies in gene-targeted mice establish that SAA contributes to atherosclerosis and some metastatic cancers. Accumulating evidence indicates that the lipidation state of SAA profoundly affects its bioactivities, with lipid-poor, but not HDL-associated, SAA capable of …

Genetic Transformation In Cryptococcus Species, Ping Wang

School of Medicine Faculty Publications

Genetic transformation plays an imperative role in our understanding of the biology in unicellular yeasts and filamentous fungi, such as Saccharomyces cerevisiae, Aspergillus nidulans, Cryphonectria parasitica, and Magnaporthe oryzae. It also helps to understand the virulence and drug resistance mechanisms of the pathogenic fungus Cryptococcus that causes cryptococcosis in health and immunocompromised individuals. Since the first attempt at DNA transformation in this fungus by Edman in 1992, various methods and techniques have been developed to introduce DNA into this organism and improve the efficiency of homology-mediated gene disruption. There have been many excellent summaries or reviews covering the subject. Here …

Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1 …

'Educated' Osteoblasts Reduce Osteoclastogenesis In A Bone-Tumor Mimetic Microenvironment., Alexus D. Kolb, Jinlu Dai, Evan T. Keller, Karen M. Bussard

Department of Cancer Biology Faculty Papers

Breast cancer (BC) metastases to bone disrupt the balance between osteoblasts and osteoclasts, leading to excessive bone resorption. We identified a novel subpopulation of osteoblasts with tumor-inhibitory properties, called educated osteoblasts (EOs). Here we sought to examine the effect of EOs on osteoclastogenesis during tumor progression. We hypothesized that EOs affect osteoclast development in the bone-tumor niche, leading to suppressed pre-osteoclast fusion and bone resorption. Conditioned media (CM) was analyzed for protein expression of osteoclast factors receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα) via ELISA. EOs were co-cultured with pre-osteoclasts on …

Abnormal Nutritive Sucking As An Indicator Of Neonatal Brain Injury, Sabrina Shandley, Gilson J. Capilouto, Eleonora Tamilia, David M. Riley, Yvette R. Johnson, Christos Papadelis

Communication Sciences and Disorders Faculty Publications

A term neonate is born with the ability to suck; this neuronal network is already formed and functional by 28 weeks gestational age and continues to evolve into adulthood. Because of the necessity of acquiring nutrition, the complexity of the neuronal network needed to suck, and neuroplasticity in infancy, the skill of sucking has the unique ability to give insight into areas of the brain that may be damaged either during or before birth. Interpretation of the behaviors during sucking shows promise in guiding therapies and how to potentially repair the damage early in life, when neuroplasticity is high. Sucking …

Tumor Microenvironment: An Evil Nexus Promoting Aggressive Head And Neck Squamous Cell Carcinoma And Avenue For Targeted Therapy, Ajaz A. Bhat, Parvaiz Yousuf, Nissar A. Wani, Arshi Rizwan, Shyam S. Chauhan, Mushtaq A. Siddiqi, Davide Bedognetti, Wael El-Rifai, Michael P. Frenneaux, Surinder K. Batra, Mohammad Haris, Muzafar A. Macha

Journal Articles: Biochemistry & Molecular Biology

Head and neck squamous cell carcinoma (HNSCC) is a very aggressive disease with a poor prognosis for advanced-stage tumors. Recent clinical, genomic, and cellular studies have revealed the highly heterogeneous and immunosuppressive nature of HNSCC. Despite significant advances in multimodal therapeutic interventions, failure to cure and recurrence are common and account for most deaths. It is becoming increasingly apparent that tumor microenvironment (TME) plays a critical role in HNSCC tumorigenesis, promotes the evolution of aggressive tumors and resistance to therapy, and thereby adversely affects the prognosis. A complete understanding of the TME factors, together with the highly complex tumor-stromal interactions, …

Parenteral Fish-Oil Containing Lipid Emulsions Limit Initial Lipopolysaccharide-Induced Host Immune Responses In Preterm Pigs, William Yakah, David Ramiro-Cortijo, Pratibha Singh, Joanne Brown, Barbara Stoll, Madhulika Kulkarni, Berthe C Oosterloo, Doug Burrin, Krishna Rao Maddipati, Raina N Fichorova, Steven D Freedman, Camilia R Martin

Children’s Nutrition Research Center Staff Publications

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS—lyophilized Escherichia coli) or saline. Plasma was collected for …

Insights Into Genome Recoding From The Mechanism Of A Classic +1-Frameshifting Trna., Howard Gamper, Haixing Li, Isao Masuda, D. Miklos Robkis, Thomas Christian, Adam B. Conn, Gregor Blaha, E. James Petersson, Ruben L. Gonzalez, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

While genome recoding using quadruplet codons to incorporate non-proteinogenic amino acids is attractive for biotechnology and bioengineering purposes, the mechanism through which such codons are translated is poorly understood. Here we investigate translation of quadruplet codons by a +1-frameshifting tRNA, SufB2, that contains an extra nucleotide in its anticodon loop. Natural post-transcriptional modification of SufB2 in cells prevents it from frameshifting using a quadruplet-pairing mechanism such that it preferentially employs a triplet-slippage mechanism. We show that SufB2 uses triplet anticodon-codon pairing in the 0-frame to initially decode the quadruplet codon, but subsequently shifts to the +1-frame during tRNA-mRNA translocation. SufB2 …

Functional Cooperativity Between The Trigger Factor Chaperone And The Clpxp Proteolytic Complex, Kamran Rizzolo, Angela Yeou Hsiung Yu, Adedeji Ologbenla, Sa Rang Kim, Haojie Zhu, Koichiro Ishimori, Guillaume Thibault, Elisa Leung, Yi Wen Zhang, Mona Teng, Marta Haniszewski, Noha Miah, Sadhna Phanse, Zoran Minic, Sukyeong Lee, Julio Diaz Caballero, Mohan Babu, Francis T F Tsai, Tomohide Saio, Walid A Houry

Faculty, Staff and Students Publications

A functional association is uncovered between the ribosome-associated trigger factor (TF) chaperone and the ClpXP degradation complex. Bioinformatic analyses demonstrate conservation of the close proximity of tig, the gene coding for TF, and genes coding for ClpXP, suggesting a functional interaction. The effect of TF on ClpXP-dependent degradation varies based on the nature of substrate. While degradation of some substrates are slowed down or are unaffected by TF, surprisingly, TF increases the degradation rate of a third class of substrates. These include λ phage replication protein λO, master regulator of stationary phase RpoS, and SsrA-tagged proteins. Globally, TF acts to …

Week Of January 11, 2021, New York Medical College

InTouch

• D.P.T. Class of 2021 TeamGO Sends Humanitarian Aid to Dominica
• Bench-to-Bedside Seminar Series Focuses on Data, Personalization and Digital Health
• Ninth Symposium on COVID-19 Set for January 12
• Chancellor Halperin Shares his Thoughts on the Medical Ethics of Vaccine Distribution

Myc Regulates Ribosome Biogenesis And Mitochondrial Gene Expression Programs Through Its Interaction With Host Cell Factor-1., Tessa M. Popay, Jing Wang, Clare M. Adams, Gregory Caleb Howard, Simona G. Codreanu, Stacy D. Sherrod, John A. Mclean, Lance R. Thomas, Shelly L. Lorey, Yuichi J. Machida, April M. Weissmiller, Christine M. Eischen, Qi Liu, William P. Tansey

Department of Cancer Biology Faculty Papers

The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)-1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC-HCF-1 interaction influences cell growth, metabolite profiles, global …

Mitochondria Exert Age-Divergent Effects On Recovery From Spinal Cord Injury, Andrew N. Stewart, Katelyn E. Mcfarlane, Hemendra J. Vekaria, William M. Bailey, Stacey A. Slone, Lauren A. Tranthem, Bei Zhang, Samir P. Patel, Patrick G. Sullivan, John C. Gensel

Physiology Faculty Publications

The extent that age-dependent mitochondrial dysfunction drives neurodegeneration is not well understood. This study tested the hypothesis that mitochondria contribute to spinal cord injury (SCI)-induced neurodegeneration in an age-dependent manner by using 2,4-dinitrophenol (DNP) to uncouple electron transport, thereby increasing cellular respiration and reducing reactive oxygen species (ROS) production. We directly compared the effects of graded DNP doses in 4- and 14-month-old (MO) SCI-mice and found DNP to have increased efficacy in mitochondria isolated from 14-MO animals. In vivo, all DNP doses significantly exacerbated 4-MO SCI neurodegeneration coincident with worsened recovery. In contrast, low DNP doses (1.0-mg/kg/day) improved tissue …