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Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions …

Gene Expression Analysis Of A Murine Model With Pulmonary Vascular Remodeling Compared To End-Stage Ipah Lungs, Kayoko Shimodaira, Yoichiro Okubo, Eri Ochiai, Haruo Nakayama, Harutaka Katano, Megumi Wakayama, Minoru Shinozaki, Takao Ishiwatari, Daisuke Sasai, Naobumi Tochigi, Tetsuo Nemoto, Tsutomu Saji, Katsuhiko Kamei, Kazutoshi Shibuya

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our …

Protocol For A Randomized Controlled Trial Evaluating The Effect Of Physical Activity On Delaying The Progression Of White Matter Changes On Mri In Older Adults With Memory Complaints And Mild Cognitive Impairment: The Aibl Active Trial, E V Cyarto, N T Lautenschlager, P M Desmond, D Ames, C Szoeke, O Salvado, Matthew Sharman, Kathryn A Ellis, P M Phal, C L Masters, C C Rowe, Ralph Martins, Kay L Cox

Research outputs 2012

Background: Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. Vascular risk factors (VRF), including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with VRF, SMC and cognitive impairment. Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function, but few studies are investigating these benefits in high-risk populations. …

Thr 163 Phosphorylation Causes Mcl-1 Stabilization When Degradation Is Independent Of The Adjacent Gsk3-Targeted Phosphodegron, Promoting Drug Resistance In Cancer, Shanna K. Nifoussi, Julie A. Vrana, Aaron M. Domina, Alfredo De Biasio, Jingang Gui, Mark A. Gregory, Stephen R. Hann, Ruth W. Craig

Dartmouth Scholarship

The antiapoptotic Bcl-2 family member Mcl-1 is a PEST protein (containing sequences enriched in proline, glutamic acid, serine, and threonine) and is subject to rapid degradation via multiple pathways. Impaired degradation leading to the maintenance of Mcl-1 expression is an important determinant of drug resistance in cancer. Phosphorylation at Thr 163 in the PEST region, stimulated by 12-O-tetradecanoylphorbol acetic acid (TPA)-induced activation of extracellular signal-regulated kinase (ERK), is associated with Mcl-1 stabilization in BL41-3 Burkitt lymphoma cells. This contrasts with the observation that Thr 163 phosphorylation in normal fibroblasts primes glycogen synthase kinase (GSK3)-induced phosphorylation at Ser 159, producing a …

Influenza-Infected Neutrophils Within The Infected Lungs Act As Antigen Presenting Cells For Anti-Viral Cd8+ T Cells, Matthew M. Hufford, Graham Richardson, Haixia Zhou, Balaji Manicassamy, Adolfo Garcia-Sastre, Richard I. Enelow, Thomas J. Braciale

Dartmouth Scholarship

Influenza A virus (IAV) is a leading cause of respiratory tract disease worldwide. Anti-viral CD8⁺ T lymphocytes responding to IAV infection are believed to eliminate virally infected cells by direct cytolysis but may also contribute to pulmonary inflammation and tissue damage via the release of pro-inflammatory mediators following recognition of viral antigen displaying cells. We have previously demonstrated that IAV antigen expressing inflammatory cells of hematopoietic origin within the infected lung interstitium serve as antigen presenting cells (APC) for infiltrating effector CD8⁺ T lymphocytes; however, the spectrum of inflammatory cell types capable of serving as APC was not …

Algorithmic Decomposition Of Shuffle On Words, Franziska Biegler, Mark Daley, Ian Mcquillan

Brain and Mind Institute Researchers' Publications

We investigate shuffle-decomposability into two words. We give an algorithm which takes as input a DFA M (under certain conditions) and determines the unique candidate decomposition into words u and v such that L(M) = u v ifM is shuffle decomposable, in time O(|u| + |v|). Even though this algorithm does not determine whether or not the DFA is shuffle decomposable, the sublinear time complexity of only determining the two words under the assumption of decomposability is surprising given the complexity of shuffle, and demonstrates an interesting property of the operation. We also show that for given words u and …

On The Genetic And Environmental Associations Between Body Composition, Depression Symptoms And Smoking Behavior., Roseann Peterson

Theses and Dissertations

Obesity is a serious public health crisis and recent estimates of its incidence are the highest in United States history, with 35% and 17% of American adults and children affected, respectively. The clinical definition of adult obesity is operationalized as a body mass index (BMI) greater than 30 kg/m2. Although the prevalence of common obesity has increased dramatically over the past 30 years–largely thought to be due to changes in the environment, such as high calorie diets and sedentary lifestyles—twin and family studies have shown consistently that relative body weight is under considerable genetic influence in both children and adults, …

We Are… Bridging Medicine And Science Vol. 1, Issue 2, Fall 2012, Marshall University Biomedical Sciences

We Are... Bridging Medicine Science

No abstract provided.

Cdk Inhibitors (P16/P19/P21) Induce Senescence And Autophagy In Cancer-Associated Fibroblasts, "Fueling" Tumor Growth Via Paracrine Interactions, Without An Increase In Neo-Angiogenesis., Claudia Capparelli, Barbara Chiavarina, Diana Whitaker-Menezes, Timothy G Pestell, Richard Pestell, James Hulit, Sebastiano Andò, Anthony Howell, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P. Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Here, we investigated the compartment-specific role of cell cycle arrest and senescence in breast cancer tumor growth. For this purpose, we generated a number of hTERT-immortalized senescent fibroblast cell lines overexpressing CDK inhibitors, such as p16(INK4A), p19(ARF) or p21(WAF1/CIP1). Interestingly, all these senescent fibroblast cell lines showed evidence of increased susceptibility toward the induction of autophagy (either at baseline or after starvation), as well as significant mitochondrial dysfunction. Most importantly, these senescent fibroblasts also dramatically promoted tumor growth (up to ~2-fold), without any comparable increases in tumor angiogenesis. Conversely, we generated human breast cancer cells (MDA-MB-231 cells) overexpressing CDK inhibitors, …

An Analysis Of The Incidence Of Antibiotic Resistant Infections In The State Of New Hampshire, Melanie Duhamel

Honors Theses and Capstones

The purpose of this research paper is to study, analyze, and characterize antibiotic resistance in both the theoretical and investigative contexts. After an in-depth examination of the literature and previous research investigating the definition, origin, affected organisms, and proposed coping mechanisms related to antibiotic resistance, a research plan was organized and executed.

The organism Methicillin Resistant Staphylococcus aureus (MRSA) was selected as the focus of study because of abundant current research and regulated monitoring of this organism in healthcare organizations. Data about the incidence rates of MRSA in theUnited States was collected from reports disseminated by the Center for Disease …

Immune Clearance Of Attenuated Rabies Virus Results In Neuronal Survival With Altered Gene Expression., Emily A Gomme, Christoph Wirblich, Sankar Addya, Glenn F Rall, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

Rabies virus (RABV) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. However, whether or not neurons survive infection and clearance and, provided they do, whether they are functionally restored to their pre-infection phenotype has not been determined in vivo for RABV, or any neurotropic virus. This is due, in part, …

Neurosteroid-Mediated Regulation Of Brain Innate Immunity In Hiv/Aids: Dhea-S Suppresses Neurovirulence, Amber Paul, Ferdinand G. Maingat, Maria J. Polyak, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, Christopher Power

Publications

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid mediated effects and lentivirus infection outcomes. Analyses of HIV-infected uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV macrophages exhibited suppressed enzyme expression without …

Phase Ii Evaluation Of Dasatinib In The Treatment Of Recurrent Or Persistent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study., Russell J Schilder, William E Brady, Heather A Lankes, James V Fiorica, Mark S Shahin, Xun C Zhou, Robert S Mannel, Harsh B Pathak, Wei Hu, R Katherine Alpaugh, Anil K Sood, Andrew K Godwin

Department of Medical Oncology Faculty Papers

OBJECTIVES: Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome.

METHODS: Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease …

Pediatric Pharmacogenomics: A Systematic Assessment Of Ontogeny And Genetic Variation To Guide The Design Of Statin Studies In Children., Jonathan B. Wagner, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The dose-exposure-response relationship for drugs may differ in pediatric patients compared with adults. Many clinical studies have established drug dose-exposure relationships across the pediatric age spectrum; however, genetic variation was seldom included. This article applies a systematic approach to determine the relative contribution of development and genetic variation on drug disposition and response using HMG-CoA reductase inhibitors as a model. Application of the approach drives the collection of information relevant to understanding the potential contribution of ontogeny and genetic variation to statin dose-exposure-response in children, and identifies important knowledge deficits to be addressed through the design of future studies.

Nonthermal Plasma Jet Efficacy On Candida Kefyr, Amber Marie Mattson Jackson

Electrical & Computer Engineering Theses & Dissertations

The inactivation abilities of a nonthermal plasma jet were investigated with the yeast C. kefyr, a pathogen with increasing importance in healthcare. The plasma is generated using a microhollow cathode discharge (MHCD) geometry operated with a DC voltage of 2 kV and a current of 30 mA using air as the operating gas at an airflow rate of 8 SLM. The plasma discharge approaches room temperature at a few mm away from the plasma jet allowing for the use on heat sensitive surfaces. Dry air and humid air were used as the operating gas to see if humidity plays …

Examining Alcohol Dependence And Its Correlates From A Genetically Informative Perspective, Laura Hack

Theses and Dissertations

Alcohol dependence (AD) is a serious and common public health problem that contributes to great societal, medical, and legal costs. It has taken work from multiple disciplines, including developmental psychology, genetic epidemiology, and molecular genetics, to achieve our current understanding of environmental and genetic risk factors for AD as well as its variable developmental trajectories. Nevertheless, there is still much to be learned in order to improve treatment outcomes. One approach to augmenting our understanding of this disorder is through genetically informative study designs that either examine risk in aggregate or assess specific susceptibility variants. In this dissertation, we utilize …

Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms In Angiotensin Ii-Infused Mice, Xiaojie Xie, Hong Lu, Jessica J. Moorleghen, Deborah A. Howatt, Debra L. Rateri, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Background: There is no proven medical approach to attenuating expansion and rupture of abdominal aortic aneurysms (AAAs). One approach that is currently being investigated is the use of doxycycline. Despite being primarily used as an antimicrobial drug, doxycycline has been proposed to function in reducing AAA expansion. Doxycycline is effective in reducing the formation in the most commonly used mouse models of AAAs when administered prior to the initiation of the disease. The purpose of the current study was to determine the effects of doxycycline on established AAAs when it was administered at a dose that produces therapeutic serum …

Latexin Is Down-Regulated In Hematopoietic Malignancies And Restoration Of Expression Inhibits Lymphoma Growth, Yi Liu, Dianna Howard, Kyle Rector, Carol Swiderski, Jason Brandon, Lawrence Schook, Jayesh Mehta, J. Scott Bryson, Subbarao Bondada, Ying Liang

Internal Medicine Faculty Publications

Latexin is a negative regulator of hematopoietic stem cell number in mice. Its dysregulated expression in other tumors led us to hypothesize that latexin may have tumor suppressor properties in hematological malignancies. We found that latexin was down-regulated in a variety of leukemia and lymphoma cell lines as well as in CD34+ cells from the blood and marrow of patients with these malignancies. 5-aza-2'-deoxycytodine treatment and bisulfite sequencing revealed hypermethylation of latexin promoter in tumor cells. Retrovirus-mediated latexin overexpression in A20 mouse lymphoma cells inhibited their in vitro growth by 16 fold and in vivo tumor volume by 2 fold. …

Using Genetic Information In Risk Prediction For Alcohol Dependence, Jia Yan

Theses and Dissertations

Family-based and genome-wide association studies (GWAS) of alcohol dependence (AD) have reported numerous associated variants. The clinical validity of these variants for predicting AD compared to family history has not yet been reported. These studies aim to explore the aggregate impact of multiple genetic variants with small effect sizes on risk prediction in order to provide a clinical interpretation of genetic contributions to AD. Data simulations showed that given AD’s prevalence and heritability, a risk prediction model incorporating all genetic contributions would have an area under the receiver operating characteristic curve (AUC) approaching 0.80, which is often a target AUC …

Ultraviolet Radiation–Induced Cataract In Mice: The Effect Of Age And The Potential Biochemical Mechanism, Jie Zhang, Hong Yan, Stefan Lofgren, Xiaoli Tian, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. To study the effect of age on the morphologic and biochemical alterations induced by in vivo exposure of ultraviolet radiation (UV).

METHODS. Young and old C57BL/6 mice were exposed to broadband UVBþUVA and euthanized after 2 days. Another batch of UV-exposed young mice was monitored for changes after 1, 2, 4, and 8 days. Age-matched nonexposed mice served as controls. Lens changes were documented in vivo by slit-lamp biomicroscopy and dark field microscopy photographs ex vivo. Lens homogenates were analyzed for glutathione (GSH) level, and the activities of thioredoxin (Trx), thioltransferase (TTase), and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Glutathionylated lens proteins …

Metabolic Remodeling Of The Tumor Microenvironment: Migration Stimulating Factor (Msf) Reprograms Myofibroblasts Toward Lactate Production, Fueling Anabolic Tumor Growth., Valentina Carito, Gloria Bonuccelli, Ubaldo E Martinez-Outschoorn, Diana Whitaker-Menezes, Maria Cristina Caroleo, Erika Cione, Anthony Howell, Richard G Pestell, Michael P. Lisanti, Federica Sotgia

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Migration stimulating factor (MSF) is a genetically truncated N-terminal isoform of fibronectin that is highly expressed during mammalian development in fetal fibroblasts, and during tumor formation in human cancer-associated myofibroblasts. However, its potential functional role in regulating tumor metabolism remains unexplored. Here, we generated an immortalized fibroblast cell line that recombinantly overexpresses MSF and studied their properties relative to vector-alone control fibroblasts. Our results indicate that overexpression of MSF is sufficient to confer myofibroblastic differentiation, likely via increased TGF-b signaling. In addition, MSF activates the inflammation-associated transcription factor NFκB, resulting in the onset of autophagy/mitophagy, thereby driving glycolytic metabolism (L-lactate …

Expression Of Muc17 Is Regulated By Hif1Α-Mediated Hypoxic Responses And Requires A Methylation-Free Hypoxia Responsible Element In Pancreatic Cancer., Sho Kitamoto, Seiya Yokoyama, Michiyo Higashi, Norishige Yamada, Shyuichiro Matsubara, Sonshin Takao, Surinder K. Batra, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinomas (PDACs); however, the exact regulatory mechanism of MUC17 expression has yet to be identified. Here, we provide the first report of the MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor microenvironment and a driving force of cancer progression. Our data revealed that MUC17 was significantly induced by hypoxic stimulation through a hypoxia-inducible factor 1α (HIF1α)-dependent pathway in some pancreatic cancer cells (e.g., …

Phthalate Exposure Changes The Metabolic Profile Of Cardiac Muscle Cells, Nikki G. Posnack, Luther M. Swift, Matthew W. Kay, Norman H. Lee, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background: Phthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown.

Objectives: We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardiomyocytes because alterations in metabolic processes can lead to cell dysfunction.

Methods: Neonatal rat cardiomyocytes were treated with DEHP at a concentration and duration comparable to clinical exposure (50–100 μg/mL, 72 hr). We assessed the effect of DEHP on gene expression using microarray analysis. Physiological responses …

Oxygen Glucose Deprivation In Rat Hippocampal Slice Cultures Results In Alterations In Carnitine Homeostasis And Mitochondrial Dysfunction, Thomas Rau, Qing Lu, Shruti Sharma, Xutong Sun, Gregory Leary, Matthew L. Beckman, Yal Hou, Mark S. Wainwright, Michael P. Kavanaugh, David J. Poulsen, Stephen M. Black

Biomedical and Pharmaceutical Sciences Faculty Publications

Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we …

Inflammation, Organomegaly, And Muscle Wasting Despite Hyperphagia In A Mouse Model Of Burn Cachexia., Felipe E Pedroso, Paul B Spalding, Michael C Cheung, Relin Yang, Juan C Gutierrez, Andrea Bonetto, Rui Zhan, Ho Lam Chan, Nicholas Namias, Leonidas G Koniaris, Teresa A Zimmers

Department of Cancer Biology Faculty Papers

BACKGROUND: Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking.

METHODS: Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and …

Herpes Simplex Virus 34.5 Interferes With Autophagosome Maturation And Antigen Presentation In Dendritic Cells, Philipe A. M. Gobeil, David A. Leib

Dartmouth Scholarship

The cellular autophagy response induced by herpes simplex virus 1 (HSV-1) is countered by the viral γ34.5 protein. γ34.5 modulates autophagy by binding to the host autophagy protein Beclin-1 and through this binding inhibits the formation of autophagosomes in fibroblasts and neurons. In contrast, in this study dendritic cells (DCs) infected with HSV-1 showed an accumulation of autophagosomes and of the long-lived protein p62. No such accumulations were observed in DCs infected with a γ34.5-null virus or a virus lacking the Beclin-binding domain (BBD) of γ34.5. To explore this further, we established stably transduced DC lines to show that γ34.5 …

Increased Susceptibility To Metabolic Syndrome In Adult Offspring Of Angiotensin Type 1 Receptor Autoantibody-Positive Rats., Suli Zhang, Xi Zhang, Lihong Yang, Zi Yan, Li Yan, Jue Tian, Xiaoyu Li, Li Song, Li Wang, Xiaoli Yang, Ronghua Zheng, Wayne Bond Lau, Xinliang Ma, Huirong Liu

Department of Emergency Medicine Faculty Papers

Abstract Aims: Abnormal fetal and early postnatal growth is closely associated with adult-onset metabolic syndrome (MetS). However, the underlying etiological factors remain complex. The presence of the autoantibody against the angiotensin II type 1 receptor (AT1-Ab), a known risk factor for pre-eclampsia, may create a suboptimal intrauterine fetal environment. The current study investigated whether middle-aged offspring of AT1-Ab-positive mothers were prone to metabolic disorder development. Results: The AT1-Abs was detected in placental trophoblastic cells, capillary endothelium, and milk of pregnant rats actively immunized with the second extracellular loop of the AT1 receptor. AT1-Abs in newborn rats induced vasoconstriction, increased intracellular-free …

Global Cellular Regulation Including Cardiac Function By Post-Translational Protein Arginylation., Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

In this issue a very significant contribution to cardiology describing critical roles of ATE1 appears by Kurosaka et al. [1]. In view of this paper, as the discoverers of ATE1, we have been asked to contribute an article (editorial) regarding ATE1 (enzyme which transfers arginine from arginyl tRNA to protein acceptors). This short article consists of three sections: 1) a historical anecdote describing how ATE1 was discovered; 2) its possible role in aging and cellular transformation, and most importantly; 3) its role in the development and maintenance of cardiac activity. The last section has direct bearing to the Kurosaka …

Human Endometrial Stromal Stem Cells Differentiate Into Megakaryocytes With The Ability To Produce Functional Platelets, Jinju Wang, Shuzhen Chen, Cheng Zhang, Samantha Stegeman, Teresa Pfaff-Amesse, Ying Zhang, Wenfeng Zhang, Lawrence Amesse, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

Human endometrium is a high dynamic tissue that contains endometrial stromal stem cells (hESSCs). The hESSCs have been differentiated into a number of cell lineages. However, differentiation of hESSCs into megakaryocytes (MKs) has not yet been investigated. The aim of this study was to investigate the feasibility of MK generation from hESSCs and subsequent production of functional platelets (PLTs). In our study, hESSCs were cultured from endometrial stromal cells as confirmed by positive stromal cell specific markers (CD90 and CD29) and negative hematopoietic stem cell markers (CD45 and CD34) expression. Then, hESSCs were differentiated in a medium supplemented with thrombopoietin …

Exosome-Mediated Shuttling Of Microrna-29 Regulates Hiv Tat And Morphine-Mediated Neuronal Dysfunction., Guoku Hu, H Yao, A D. Chaudhuri, Sowmya V. Yelamanchili, H Wen, P D. Cheney, Howard S. Fox, Shilpa J. Buch

Journal Articles: Pharmacology & Experimental Neuroscience

Neuronal damage is a hallmark feature of HIV-associated neurological disorders (HANDs). Opiate drug abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Opiates such as morphine have been shown to enhance HIV transactivation protein Tat-mediated toxicity in both human neurons and neuroblastoma cells. In the present study, we demonstrate reduced expression of the tropic factor platelet-derived growth factor (PDGF)-B with a concomitant increase in miR-29b in the basal ganglia region of the brains of morphine-dependent simian immunodeficiency virus (SIV)-infected macaques compared with the SIV-infected controls. In vitro relevance …