Digital Commons Network^™

The G-Protein-Coupled Estrogen Receptor Agonist G-1 Suppresses Proliferation Of Ovarian Cancer Cells By Blocking Tubulin Polymerization., Cheng Wang, Xiangmin Lv, Chunbo He, G Hua, M-Y Tsai, John S. Davis

Journal Articles: Obstetrics & Gynecology

The G-protein-coupled estrogen receptor 1 (GPER) has recently been reported to mediate the non-genomic action of estrogen in different types of cells and tissues. G-1 (1-[4-(6-bromobenzo[1,3] dioxol-5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone) was developed as a potent and selective agonist for GPER. G-1 has been shown to induce the expression of genes and activate pathways that facilitate cancer cell proliferation by activating GPER. Here we demonstrate that G-1 has an anticancer potential with a mechanism similar to vinca alkaloids, the commonly used chemotherapy drugs. We found that G-1 blocks tubulin polymerization and thereby interrupts microtubule assembly in ovarian cancer cells leading to the arrest of …

Recruitment Of Tlr Adapter Trif To Tlr4 Signaling Complex Is Mediated By The Second Helical Region Of Trif Tir Domain, Wenji Piao, Lisa W. Ru, Kurt H. Piepenbrink, Eric J. Sundberg, Stefanie N. Vogel, Vladimir Y. Toshchakov

Food for Health: Publications

Toll/IL-1R resistance (TIR) domain–containing adapter-inducing IFN-β (TRIF) is a Toll-like receptor (TLR) adapter that mediates MyD88-independent induction of type I interferons through activation of IFN regulatory factor 3 and NFκB. We have examined peptides derived from the TRIF TIR domain for ability to inhibit TLR4. In addition to a previously identified BB loop peptide (TF4), a peptide derived from putative helix B of TRIF TIR (TF5) strongly inhibits LPS-induced cytokine and MAPK activation in wild-type cells. TF5 failed to inhibit LPS-induced cytokine and kinase activation in TRIF-deficient immortalized bone-marrow–derived macrophage, but was fully inhibitory in MyD88 knockout cells. TF5 does …

Combination Of Necroptosis And Apoptosis Inhibition Enhances Cardioprotection Against Myocardial Ischemia-Reperfusion Injury., Shizuka Koshinuma, Masami Miyamae, Kazuhiro Kaneda, Junichiro Kotani, Vincent M. Figueredo

Division of Cardiology Faculty Papers

PURPOSE: Necroptosis has been proposed as a mode of cell death that is a caspase-independent programmed necrosis. We investigated whether necroptosis is involved in myocardial ischemia-reperfusion injury in isolated guinea pig hearts and, if so, whether simultaneous inhibition of necroptosis and apoptosis confers enhanced cardioprotection.

METHODS: Isolated perfused guinea pig hearts were subjected to 30 min ischemia and 4 h reperfusion (control = CTL, n = 8). Necrostatin-1 (necroptosis inhibitor, 10 μM), Z-VAD (apoptosis inhibitor, 0.1 μM) and both inhibitors were administered starting 5 min before ischemia and during the initial 30 min of reperfusion (Nec, Z-VAD, Nec + Z-VAD; …

Fn14•Trail Effectively Inhibits Hepatocellular Carcinoma Growth., Alexandra Aronin, Shira Amsili, Tatyana B Prigozhina, Kobi Tzdaka, Jacob Rachmilewitz, Noam Shani, Mark L Tykocinski, Michal Dranitzki Elhalel

Department of Medical Genetics Faculty Papers

BACKGROUND: New strategies for the treatment of hepatocellular carcinoma (HCC) are needed, given that currently available chemotherapeutics are inefficient. Since tumor growth reflects the net balance between pro-proliferative and death signaling, agents shifting the equilibrium toward the latter are of considerable interest. The TWEAK:Fn14 signaling axis promotes tumor cell proliferation and tumor angiogenesis, while TRAIL:TRAIL-receptor (TRAIL-R) interactions selectively induce apoptosis in malignant cells. Fn14•TRAIL, a fusion protein bridging these two pathways, has the potential to inhibit tumor growth, by interfering with TWEAK:Fn14 signaling, while at the same time enforcing TRAIL:TRAIL-R-mediated apoptosis. Consequently, Fn14•TRAIL's capacity to inhibit HCC growth was tested. …

Marijuana: Current Concepts, Donald E. Greydanus, Elizabeth K. Hawver, Megan M. Greydanus, Joav Merrick

Pediatrics Faculty Publications

Marijuana (cannabis) remains a controversial drug in the twenty-first century. This paper considers current research on use of Cannabis sativa and its constituents such as the cannabinoids. Topics reviewed include prevalence of cannabis (pot) use, other drugs consumed with pot, the endocannabinoid system, use of medicinal marijuana, medical adverse effects of cannabis, and psychiatric adverse effects of cannabis use. Treatment of cannabis withdrawal and dependence is difficult and remains mainly based on psychological therapy; current research on pharmacologic management of problems related to cannabis consumption is also considered. The potential role of specific cannabinoids for medical benefit will be revealed …

A Preliminary Report Of Percutaneous Craniofacial Osteoplasty In A Rat Calvarium., William Parkes, Jewel Greywoode, Brian J O'Hara, Ryan N. Heffelfinger, Howard Krein

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: To evaluate the potential for injectable, permanent bone augmentation by assessing the biocompatability and bioactivity of subperiosteal hydroxylapatite (Radiesse) deposition in a rat model.

STUDY DESIGN: Randomized controlled animal model METHODS: Fourteen adult Sprague Dawley rats were injected in the parietal skull with 0.2 ml of hydroxylapatite (10 animals) or a carrier gel control (4 animals), using a subperiosteal injection technique on the right and a subcutaneous injection technique on the left. At 1, 3, and 6 months, 3 rats (1 negative control, 2 variables) were sacrificed and calvaria were harvested. At 12 months, the remaining 5 rats were …

Development Of A Conditional Mesd (Mesoderm Development) Allele For Functional Analysis Of The Low-Density Lipoprotein Receptor-Related Family In Defined Tissues, Andrew V. Taibi, Janet K. Lighthouse, Richard C. Grady, Kenneth R. Shroyer, Bernadette Holdener

Department of Biomedical Engineering Faculty Publications

The Low-density lipoprotein receptor-Related Protein (LRP) family members are essential for diverse processes ranging from the regulation of gastrulation to the modulation of lipid homeostasis. Receptors in this family bind and internalize a diverse array of ligands in the extracellular matrix (ECM). As a consequence, LRPs regulate a wide variety of cellular functions including, but not limited to lipid metabolism, membrane composition, cell motility, and cell signaling. Not surprisingly, mutations in single human LRPs are associated with defects in cholesterol metabolism and development of atherosclerosis, abnormalities in bone density, or aberrant eye vasculature, and may be a contributing factor in …

Recommendations For High-Priority Research On Cancer-Related Fatigue In Children And Adults., Andrea M. Barsevick, Michael R. Irwin, Pamela Hinds, Andrew Miller, Ann Berger, Paul Jacobsen, Sonia Ancoli-Israel, Bryce B Reeve, Karen Mustian, Ann O'Mara, Jin-Shei Lai, Michael Fisch, David Cella

Department of Medical Oncology Faculty Papers

Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current …

Retinal Angiogenesis Suppression Through Small Molecule Activation Of P53, Sai H. Chavala, Younghee Kim, Laura Tudisco, Valeria Cicatiello, Till Milde, Nagaraj Kerur, Nidia Claros, Susan Yanni, Victor H. Guaiquil, William W. Hauswirth, John S. Penn, Shahin Rafii, Sandro De Falco, Thomas C. Lee, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels …

National Trends In C. Difficileinfections In Hospitalized Children And Young Adults With Inflammatory Bowel Disease, 2001 –2010, Kelly C. Sandberg, Matthew M. Davis, Achamyeleh Gebremariam, Jeremy Adler, Child Health Evaluation And Research Unit, University Of Michigan, C.S. Mott Children's Hospital, Pediatric Gastroenterology, University Of Michigan

Pediatrics Faculty Publications

Clostridium difficile infection complicates inflammatory bowel disease in children and adults. Increased hospitalizations have been reported due to recent hypervirulent c. difficile strains. National trends of c. difficile infections in hospitalized children and young adults with inflammatory bowel disease (IBD) are currently incomplete.

La Feminización De La Especialidad De Pediatría En La Ciudad De Buenos Aires, Argentina / The Feminization Of The Specialty Of Pediatrics In The City Of Buenos Aires, Argentina, Jessica Wilder

Independent Study Project (ISP) Collection

Background: In the context of feminization of pediatrics that is occurring rapidly worldwide, this investigation seeks to determine the underlying causes of the phenomenon in Argentina. It focuses on the field of pediatrics because pediatrics is one of the most feminized medical specialties. Through this narrowed focus, the investigation intends to suggest causes for the feminization occurring in all of medicine. It studies the pediatricians of the Autonomous City of Buenos Aires in order to illuminate the social, logistical, and personal motivations that attracted them to pediatrics. It is very important to discover these motivations and causes because they reflect …

Selling Art: An Empirical Assessment Of Advertising On Fertility Clinics' Websites, Jim Hawkins

Indiana Law Journal

Scholarship on assisted reproductive technologies (ART) has emphasized the commercial nature of the interaction between fertility patients and their physicians, but little attention has been paid to precisely how clinics persuade patients to choose their clinics over their competitors’. This Article offers evidence about how clinics sell ART based on clinics’ advertising on their websites. To assess clinics’ marketing efforts, I coded advertising information on 372 fertility clinics’ websites. The results from the study confirm some suspicions of prior ART scholarship while contradicting others. For instance, in line with scholars who are concerned that racial minorities face barriers to accessing …

Altered Cholesterol Metabolism In Human Cancers Unraveled By Label-Free Spectroscopic Imaging, Shuhua Yue

Open Access Dissertations

Despite tremendous scientific achievements, cancer remains the second leading cause of death in the United States. Metabolic reprogramming has been increasingly recognized as a core hallmark of cancer. My dissertation work identified novel diagnostic markers and therapeutic targets for human cancers through the study of cholesterol in cancer cells.

Enabled by label-free Raman spectromicroscopy, we performed the first quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases, but not in normal prostate, benign prostatic hyperplasia, or …

Sevoflurane Confers Additive Cardioprotection To Ethanol Preconditioning Associated With Enhanced Phosphorylation Of Glycogen Synthase Kinase-3Β And Inhibition Of Mitochondrial Permeability Transition Pore Opening., Anna Onishi, Masami Miyamae, Hiroshi Inoue, Kazuhiro Kaneda, Chika Okusa, Yoshitaka Inamura, Mayumi Shiomi, Shizuka Koshinuma, Yoshihiro Momota, Vincent M. Figueredo

Division of Cardiology Faculty Papers

OBJECTIVE: The purposes of this study were to investigate whether sevoflurane (SEVO) enhances moderate-dose ethanol (EtOH) preconditioning and whether this additional cardioprotection is associated with glycogen synthase kinase-3β (GSK-3β), protein kinase B (Akt), mammalian target of rapamycin (mTOR), 70-kDa ribosomal s6 kinase-1 (p70s6K), and/or mitochondrial permeability transition pore (MPTP) opening.

DESIGN: In vitro study using an isolated heart Langendorff preparation.

SETTING: University research laboratory.

PARTICIPANTS: Male guinea pigs (n = 170).

INTERVENTIONS: Isolated perfused guinea pig hearts underwent 30-minute ischemia and 120-minute reperfusion (control). The EtOH group received 5% EtOH in the drinking water for 8 weeks. Anesthetic preconditioning was …

Dia-Beat-It: An Online Game For Children And Teenagers With Type 1 Diabetes, Emily M. Stone

Honors Theses and Capstones

No abstract provided.

Seventeenth Annual Scientific Meeting Institute Of Cardiovascular Science And Medicine

Journal of the Hong Kong College of Cardiology

No abstract provided.

Allograft Reconstruction For Digital Nerve Loss., John S Taras, Nirav Amin, Nimit Patel, Lucy A Mccabe

Department of Orthopaedic Surgery Faculty Papers

PURPOSE: To investigate the outcomes of digital nerve repairs using processed nerve allograft for defects measuring 30 mm or less.

METHODS: Seventeen patients with 21 digital nerve lacerations in the hand underwent reconstruction with processed nerve allograft. Outcome data for 14 patients with 18 digital nerve lacerations were available for analysis. Postoperative outcome data were recorded at a minimum of 12 months and an average of 15 months. The average nerve gap measured 11 mm (range, 5-30 mm). Outcome measures included postoperative sensory examination as assessed by Semmes-Weinstein monofilaments and static and moving 2-point discrimination. Pain was graded using a …

Is There A Viability-Vulnerability Tradeoff? Sex Differences In Fetal Programming, Curt A. Sandman, Laura M. Glynn, Elyssia Poggi Davis

Psychology Faculty Articles and Research

OBJECTIVE: In this paper we evaluate the evidence for sex differences in fetal programming within the context of the proposed viability-vulnerability tradeoff.

METHODS: We briefly review the literature on the factors contributing to primary and secondary sex ratios. Sex differences in fetal programming are assessed by summarizing previously published sex difference findings from our group (6 studies) and also new analyses of previously published findings in which sex differences were not reported (6 studies).

RESULTS: The review and reanalysis of studies from our group are consistent with the overwhelming evidence of increasing risk for viability among males exposed to environmental …

Thioredoxin Reductase Was Nitrated In The Aging Heart After Myocardial Ischemia/Reperfusion., Ke Wang, Jie Zhang, Xiaoliang Wang, Xin Liu, Lin Zuo, Kehua Bai, Jianyu Shang, Lu Ma, Teng Liu, Li Wang, Wen Wang, Xin-Liang Ma, Huirong Liu

Department of Emergency Medicine Faculty Papers

The age-related loss of anti-oxidant defense reduces recovery from myocardial ischemia/reperfusion injury (MI/R) in aged people. Our previous data showed that inactivation of thioredoxin (Trx) was involved in enhanced aging MI/R injury. Thioredoxin reductase (TrxR), the enzyme known to regulate Trx, is less efficient with age. The aim of the current study was to determine why TrxR activity was reduced and whether reduced TrxR activity contributed to enhanced aging MI/R injury. Both Trx and TrxR activity were decreased in the aging heart, and this difference was further amplified after MI/R. However, MI/R injury did not change TrxR expression between young …

Epilepsy, Hippocampal Sclerosis And Febrile Seizures Linked By Common Genetic Variation Around Scn1a., Dalia Kasperaviciute, Claudia B Catarino, Mar Matarin, Costin Leu, Jan Novy, Anna Tostevin, Bárbara Leal, Ellen V S Hessel, Kerstin Hallmann, Michael S Hildebrand, Hans-Henrik M Dahl, Mina Ryten, Daniah Trabzuni, Adaikalavan Ramasamy, Saud Alhusaini, Colin P Doherty, Thomas Dorn, Jörg Hansen, Günter Krämer, Bernhard J Steinhoff, Dominik Zumsteg, Susan Duncan, Reetta K Kälviäinen, Kai J Eriksson, Anne-Mari Kantanen, Massimo Pandolfo, Ursula Gruber-Sedlmayr, Kurt Schlachter, Eva M Reinthaler, Elisabeth Stogmann, Fritz Zimprich, Emilie Théâtre, Colin Smith, Terence J O'Brien, K Meng Tan, Slave Petrovski, Angela Robbiano, Roberta Paravidino, Federico Zara, Pasquale Striano, Michael R Sperling, Russell J Buono, Hakon Hakonarson, João Chaves, Paulo P Costa, Berta M Silva, António M Da Silva, Pierre N E De Graan, Bobby P C Koeleman, Albert Becker, Susanne Schoch, Marec Von Lehe, Philipp S Reif, Felix Rosenow, Felicitas Becker, Yvonne Weber, Holger Lerche, Karl Rössler, Michael Buchfelder, Hajo M Hamer, Katja Kobow, Roland Coras, Ingmar Blumcke, Ingrid E Scheffer, Samuel F Berkovic, Michael E. Weale, Uk Brain Expression Consortium, Norman Delanty, Chantal Depondt, Gianpiero L Cavalleri, Wolfram S Kunz, Sanjay M Sisodiya

Department of Neurology Faculty Papers

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association …

Catecholamine Interactions With The Cardiac Ryanodine Receptor, Robert Carl Klipp

Dissertations and Theses

The cardiac ryanodine receptor (RyR2) is a Ca²⁺ ion channel found in the sarcoplasmic reticulum (SR), an intracellular membranous Ca²⁺ storage system. It is well known that a destabilization of RyR2 can lead to a Ca²⁺ flux out of the SR, which results in an overload of intracellular Ca²⁺; this can also lead to arrhythmias and heart failure. The catecholamines play a large role in the regulation of RyR2; stimulation of the Beta-adrenergic receptor on the cell membrane can lead to a hyperphosphorylation of RyR2, making it more leaky to Ca²⁺. We have …

Role Of Endothelial To Mesenchymal Transition In The Pathogenesis Of The Vascular Alterations In Systemic Sclerosis., Sergio A Jimenez

Scleroderma Center Faculty Papers

The pathogenesis of Systemic Sclerosis (SSc) is extremely complex, and despite extensive studies, the exact mechanisms involved are not well understood. Numerous recent studies of early events in SSc pathogenesis have suggested that unknown etiologic factors in a genetically receptive host trigger structural and functional microvascular endothelial cell abnormalities. These alterations result in the attraction, transmigration, and accumulation of immune and inflammatory cells in the perivascular tissues, which in turn induce the phenotypic conversion of endothelial cells and quiescent fibroblasts into activated myofibroblasts, a process known as endothelial to mesenchymal transition or EndoMT. The activated myofibroblasts are the effector cells …

Asymmetric Dimethylarginine Blocks Nitric Oxide-Mediated Alcohol-Stimulated Cilia Beating., Todd A. Wyatt, S . M. Wells, Z . A. Alsaidi, Jane M. Devasure, E. B. Klein, Kristina L. Bailey, Joseph H. Sisson

Journal Articles: Pulmonary & Critical Care Med

The airway epithelium is exposed to alcohol during drinking through direct exhalation of volatized ethanol from the bronchial circulation. Alcohol exposure leads to a rapid increase in the cilia beat frequency (CBF) of bronchial epithelial cells followed by a chronic desensitization of cilia stimulatory responses. This effect is governed in part by the nitric oxide regulation of cyclic guanosine and adenosine monophosphate-dependent protein kinases (PKG and PKA) and is not fully understood. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is implicated in the pathogenesis of several pulmonary disorders. We hypothesized that the inhibition of nitric oxide synthase …

A Study On The Geophylogeny Of Clinical And Environmental Vibrio Cholerae In Kenya, J. Kiiru, A. Mutreja, A. A. Mohamed, R. W. Kimani, J. Mwituria, R. O. Sanaya, J. Muyodi, Gunturu Revathi, J. Parkhill, N. Thomson, G. Dougan, S. Kariuki

Pathology, East Africa

Cholera remains a significant public health challenge in many sub-Saharan countries including Kenya. We have performed a combination of phylogenetic and phenotypic analysis based on whole genome DNA sequences derived from 40 environmental and 57 clinical V. cholerae from different regions of Kenya isolated between 2005 and 2010. Some environmental and all clinical isolates mapped back onto wave three of the monophyletic seventh pandemic V. cholerae El Tor phylogeny but other environmental isolates were phylogenetically very distinct. Thus, the genomes of the Kenyan V. cholerae O1 El Tor isolates are clonally related to other El Tor V. cholerae isolated elsewhere …

Leukemia-Associated Rhogef (Larg) Is A Novel Rhogef In Cytokinesis And Required For The Proper Completion Of Abscission., Matthew K Martz, Elda Grabocka, Neil Beeharry, Timothy J Yen, Philip B Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Proper completion of mitosis requires the concerted effort of multiple RhoGEFs. Here we show that leukemia-associated RhoGEF (LARG), a RhoA-specific RGS-RhoGEF, is required for abscission, the final stage of cytokinesis, in which the intercellular membrane is cleaved between daughter cells. LARG colocalizes with α-tubulin at the spindle poles before localizing to the central spindle. During cytokinesis, LARG is condensed in the midbody, where it colocalizes with RhoA. HeLa cells depleted of LARG display apoptosis during cytokinesis with unresolved intercellular bridges, and rescue experiments show that expression of small interfering RNA-resistant LARG prevents this apoptosis. Moreover, live cell imaging of LARG-depleted …

Palliative Care For The Medically Complex Child, Melanie Anspacher, Neha H. Shah

E-Learning Modules

**From the AAMC website: Contains time-sensitive information that will likely be inaccurate, obsolete, or irrelevant by August 12, 2016**

Children with special health care needs are increasingly prevalent in US hospitals. The pediatric hospitalist is often the primary provider of inpatient care for these patients. The Complex Care Curriculum was developed to provide a multi-modal educational curriculum for providers with the overall goal of improving inpatient care for this population. The curriculum is composed primarily of a series of topic-specific learning modules. This particular resource was created to provide pediatricians with educational materials related to palliative care for the medically …

Inhibition Of Fas-Associated Death Domain-Containing Protein (Fadd) Protects Against Myocardial Ischemia/Reperfusion Injury In A Heart Failure Mouse Model., Qian Fan, Zheng M Huang, Matthieu Boucher, Xiying Shang, Lin Zuo, Henriette Brinks, Wayne Bond Lau, Jianke Zhang, J Kurt Chuprun, Erhe Gao

Department of Emergency Medicine Faculty Papers

AIM: As technological interventions treating acute myocardial infarction (MI) improve, post-ischemic heart failure increasingly threatens patient health. The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure.

METHODS: Cardiomyocyte-specific FADD knockout mice along with non-transgenic littermates (NLC) were subjected to 30 minutes myocardial ischemia followed by 7 days of reperfusion or 6 weeks of permanent myocardial ischemia via the ligation of left main descending coronary artery. Cardiac function were evaluated by echocardiography and left ventricular (LV) catheterization and cardiomyocyte death was measured by Evans blue-TTC …

Noise-Induced Tinnitus Using Individualized Gap Detection Analysis And Its Relationship With Hyperacusis, Anxiety, And Spatial Cognition, Edward Pace, Jinsheng Zhang

Communication Sciences and Disorders Faculty Research Publications

Tinnitus has a complex etiology that involves auditory and non-auditory factors and may be accompanied by hyperacusis, anxiety and cognitive changes. Thus far, investigations of the interrelationship between tinnitus and auditory and non-auditory impairment have yielded conflicting results. To further address this issue, we noise exposed rats and assessed them for tinnitus using a gap detection behavioral paradigm combined with statistically-driven analysis to diagnose tinnitus in individual rats. We also tested rats for hearing detection, responsivity, and loss using prepulse inhibition and auditory brainstem response, and for spatial cognition and anxiety using Morris water maze and elevated plus maze. We …

Neuroprotective Effect Of Arctigenin Via Upregulation Of P-Creb In Mouse Primary Neurons And Human Sh-Sy5y Neuroblastoma Cells., Nan Zhang, Qingping Wen, Lu Ren, Wenbo Liang, Yang Xia, Xiaodan Zhang, Dan Zhao, Dong Sun, Yv Hu, Haiguang Hao, Yaping Yan, Guangxian Zhang, Jingxian Yang, Tingguo Kang

Department of Neurology Faculty Papers

Arctigenin (Arc) has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y neuroblastoma cells. We found that Arc prevented cell viability loss induced by H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid (Aβ) production induced by H89 in neurons and human SH-SY5Y cells, and Arc also inhibited the presenilin 1(PS1) protein level in neurons. In addition, …

Pseudomonas Aeruginosa Exotoxin Y-Mediated Tau Hyperphosphorylation Impairs Microtubule Assembly In Pulmonary Microvascular Endothelial Cells, Ron Balczon, Nutan Prasain, Cristhiaan Ochoa, Jason Prater, Bing Zhu, Mikhail Alexeyev, Sarah Sayner, Dara W. Frank, Troy Stevens

University Faculty and Staff Publications

Pseudomonas aeruginosa uses a type III secretion system to introduce the adenylyl and guanylyl cyclase exotoxin Y (ExoY) into the cytoplasm of endothelial cells. ExoY induces Tau hyperphosphorylation and insolubility, microtubule breakdown, barrier disruption and edema, although the mechanism(s) responsible for microtubule breakdown remain poorly understood. Here we investigated both microtubule behavior and centrosome activity to test the hypothesis that ExoY disrupts microtubule dynamics. Fluorescence microscopy determined that infected pulmonary microvascular endothelial cells contained fewer microtubules than control cells, and further studies demonstrated that the microtubule-associated protein Tau was hyperphosphorylated following infection and dissociated from microtubules. Disassembly/reassembly studies determined that …