Digital Commons Network^™

Evaluation Of A Method For Nitrotyrosine Site Identification And Relative Quantitation Using A Stable Isotope-Labeled Nitrated Spike-In Standard And High Resolution Fourier Transform Ms And Ms/Ms Analysis, Kent W. Seeley, Alison R. Fertig, Craig P. Dufresne, Joao P. C. Pinho, Stanley M. Stevens Jr.

Molecular Biosciences Faculty Publications

The overproduction of reactive oxygen and nitrogen species (ROS and RNS) can have deleterious effects in the cell, including structural and possible activity-altering modifications to proteins. Peroxynitrite is one such RNS that can result in a specific protein modification, nitration of tyrosine residues to form nitrotyrosine, and to date, the identification of nitrotyrosine sites in proteins continues to be a major analytical challenge. We have developed a method by which ¹⁵N-labeled nitrotyrosine groups are generated on peptide or protein standards using stable isotope-labeled peroxynitrite (O¹⁵NOO⁻), and the resulting standard is mixed with representative samples in …

Expression Of Murine 5-Aminolevulinate Synthase Variants Causes Protoporphyrin Ix Accumulation And Light-Induced Mammalian Cell Death, Erica J. Fratz, Gregory A. Hunter, Gloria C. Ferreira

Chemistry Faculty Publications

5-Aminolevulinate synthase (ALAS; EC 2.3.1.37) catalyzes the first committed step of heme biosynthesis in animals. The erythroid-specific ALAS isozyme (ALAS2) is negatively regulated by heme at the level of mitochondrial import and, in its mature form, certain mutations of the murine ALAS2 active site loop result in increased production of protoporphyrin IX (PPIX), the precursor for heme. Importantly, generation of PPIX is a crucial component in the widely used photodynamic therapies (PDT) of cancer and other dysplasias. ALAS2 variants that cause high levels of PPIX accumulation provide a new means of targeted, and potentially enhanced, photosensitization. In order to assess …

Attitudes Toward Monsters, Jonathan R. Gaber, Suma Mallavarapu, Beth Randi Kirsner

The Kennesaw Journal of Undergraduate Research

The concept of monsters is ubiquitous across cultures, but there has been little research on monsters themselves and what factors shape people’s attitudes toward them. Kennesaw State University undergraduate psychology students (N = 450) read unbiased, positively biased, or negatively biased reports of one of 15 fictional monsters before all participants read identical stories about an encounter with the monster. Questionnaire responses indicated that reading a negatively biased report results in significantly more negative attitudes toward a monster than reading an unbiased report, that attitudes toward animals positively correlate with attitudes toward monsters, and that attitudes toward monsters differ depending …

The Gut Of Geographically Disparate Ciona Intestinalis Harbors A Core Microbiota, Larry J. Dishaw, Jaime Flores-Torres, Simon Lax, Kristina Gemayel, Brittany Leigh, Daniela Melillo, M. Gail Mueller, Lenina Natale, Ivana Zucchetti, Rosaria De Santis, Maria Rosaria Pinto, Gary W. Litman, Jack W. Gilbert

Marine Science Faculty Publications

It is now widely understood that all animals engage in complex interactions with bacteria (or microbes) throughout their various life stages. This ancient exchange can involve cooperation and has resulted in a wide range of evolved host-microbial interdependencies, including those observed in the gut. Ciona intestinalis, a filter-feeding basal chordate and classic developmental model that can be experimentally manipulated, is being employed to help define these relationships. Ciona larvae are first exposed internally to microbes upon the initiation of feeding in metamorphosed individuals; however, whether or not these microbes subsequently colonize the gut and whether or not Ciona forms …

Evidence Of Positive Selection In Mitochondrial Complexes I And V Of The African Elephant., Tabitha M. Finch, Nan Zhao, Dmitry Korkin, Katy H. Frederick, Lori S. Eggert

CVM Publications

As species evolve, they become adapted to their local environments. Detecting the genetic signature of selection and connecting that to the phenotype of the organism, however, is challenging. Here we report using an integrative approach that combines DNA sequencing with structural biology analyses to assess the effect of selection on residues in the mitochondrial DNA of the two species of African elephants. We detected evidence of positive selection acting on residues in complexes I and V, and we used homology protein structure modeling to assess the effect of the biochemical properties of the selected residues on the enzyme structure. Given …

Evidence For Aberrant Astrocyte Hemichannel Activity In Juvenile Neuronal Ceroid Lipofuscinosis (Jncl)., Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian

Journal Articles: Pathology and Microbiology

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have …

Characterization Of A Far-Red Analog Of Ghrelin For Imaging Ghs-R In P19-Derived Cardiomyocytes., Gregory A F Douglas, Rebecca Mcgirr, Carlie L Charlton, Dov B Kagan, Lisa M Hoffman, Leonard G Luyt, Savita Dhanvantari

Medical Biophysics Publications

Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as …

Comparative Analysis Of Gingival Tissue Antigen Presentation Pathways In Ageing And Periodontitis, Octavio A. Gonzalez, Michael John Novak, Sreenatha S. Kirakodu, Luis Orraca, Kuey-Chu Chen, Arnold J. Stromberg, Janis Gonzalez-Martinez, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

AIM: Gingival tissues of periodontitis lesions contribute to local elevations in mediators, including both specific T cell and antibody immune responses to oral bacterial antigens. Thus, antigen processing and presentation activities must exist in these tissues to link antigen-presenting cells with adaptive immunity. We hypothesized that alterations in the transcriptome of antigen processing and presentation genes occur in ageing gingival tissues and that periodontitis enhances these differences reflecting tissues less capable of immune resistance to oral pathogens.

MATERIALS AND METHODS: Rhesus monkeys (n = 34) from 3 to 23 years of age were examined. A buccal gingival sample from healthy …

Effects Of Incremental Amounts Of Fish Oil On Trans Fatty Acids And Butyrivibrio Bacteria In Continuous Culture Fermenters., A A Abughazaleh, A Ishlak

Peer-reviewed Articles

Previous studies have shown that adding fish oil (FO) to ruminant animal diets increased vaccenic acid (VA; t11 C18:1) accumulation in the rumen. Therefore, the objective of this study was to evaluate the effect of dietary FO amounts on selected strains of rumen bacteria involved in biohydrogenation. A single-flow continuous culture system consisting of four fermenters was used in a 4 × 4 Latin square design with four 9 days consecutive periods. Treatment diets were as follows: (i) control diet (53:47 forage to concentrate; CON), (ii) control plus FO at 0.5% (DM basis; FOL), (iii) control plus FO at 2% …

Human-Centered Environmental Values Versus Nature-Centric Environmental Values--Is This The Question?, Zygmunt J.B. Plater

Michigan Journal of Environmental & Administrative Law

The challenging background context for much of the discussion and cogitation in the panels and pages of this conference is the unfortunate fact that environmental protection law in virtually all its manifestations is currently faring rather poorly in the public policy arenas of national government. From the public health hazards of residual substances in consumer goods and human breast milk to the mighty troubles of human-caused climate disruption, many of the most significant structures of societal governance are locked in political and financial dysfunctions and impasses. Given the conference’s goal to “explore more deeply the relationship between environmental protection and …

Bisphenol A Increases Atherosclerosis In Pregnane X Receptor-Humanized Apoe Deficient Mice, Yipeng Sui, Se-Hyung Park, Robert N. Helsley, Manjula Sunkara, Frank J. Gonzalez, Andrew J. Morris, Changcheng Zhou

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA has recently been associated with increased risk of cardiovascular disease (CVD) in multiple large-scale human population studies, but the underlying mechanisms remain elusive. We previously reported that BPA activates the pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro-atherogenic effects in animal models upon activation. Interestingly, BPA is a potent agonist of human PXR but does not activate mouse or rat PXR signaling, which confounds the use of rodent models to evaluate mechanisms of BPA-mediated CVD risk. …

Gene Co-Citation Networks Associated With Worker Sterility In Honey Bees., Emma Kate Mullen, Mark Daley, Alanna Gabrielle Backx, Graham James Thompson

Brain and Mind Institute Researchers' Publications

BACKGROUND: The evolution of reproductive self-sacrifice is well understood from kin theory, yet our understanding of how actual genes influence the expression of reproductive altruism is only beginning to take shape. As a model in the molecular study of social behaviour, the honey bee Apis mellifera has yielded hundreds of genes associated in their expression with differences in reproductive status of females, including genes directly associated with sterility, yet there has not been an attempt to link these candidates into functional networks that explain how workers regulate sterility in the presence of queen pheromone. In this study we use available …

Aging Aggravates Nitrate-Mediated Ros/Rns Changes., Qian Fan, Lifen Chen, Shujuan Cheng, Fang Li, Wayne Bond Lau, Le Feng Wang, Jing Hua Liu

Department of Emergency Medicine Faculty Papers

Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50  μg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress …

Isoform- And Species-Specific Control Of Inositol 1,4,5-Trisphosphate (Ip3) Receptors By Reactive Oxygen Species., Száva Bánsághi, Tünde Golenár, Muniswamy Madesh, György Csordás, Satish P. Ramachandrarao, Kumar Sharma, David I Yule, Suresh K Joseph, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Reactive oxygen species (ROS) stimulate cytoplasmic [Ca(2+)] ([Ca(2+)]c) signaling, but the exact role of the IP3 receptors (IP3R) in this process remains unclear. IP3Rs serve as a potential target of ROS produced by both ER and mitochondrial enzymes, which might locally expose IP3Rs at the ER-mitochondrial associations. Also, IP3Rs contain multiple reactive thiols, common molecular targets of ROS. Therefore, we have examined the effect of superoxide anion (O2) on IP3R-mediated Ca(2+) signaling. In human HepG2, rat RBL-2H3, and chicken DT40 cells, we observed [Ca(2+)]c spikes and frequency-modulated oscillations evoked by a O2 donor, xanthine (X) + xanthine oxidase (XO), dose-dependently. …

Integrated Assessment Of Predicted Mhc Binding And Cross-Conservation With Self Reveals Patterns Of Viral Camouflage, Lu He, Anne S. De Groot, Andres H. Gutierrez, William D. Martin, Lenny Moise, Chris Bailey-Kellogg

Dartmouth Scholarship

Immune recognition of foreign proteins by T cells hinges on the formation of a ternary complex sandwiching a constituent peptide of the protein between a major histocompatibility complex (MHC) molecule and a T cell receptor (TCR). Viruses have evolved means of "camouflaging" themselves, avoiding immune recognition by reducing the MHC and/or TCR binding of their constituent peptides. Computer-driven T cell epitope mapping tools have been used to evaluate the degree to which articular viruses have used this means of avoiding immune response, but most such analyses focus on MHC-facing ‘agretopes'. Here we set out a new means of evaluating the …

Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to …

The Merg1a Channel Modulates Skeletal Muscle Murf1, But Not Mafbx, Expression., Amber L Pond, Carrie Nedele, Wen-Horng Wang, Xun Wang, Claire Walther, Christine Jaeger, Kevin S Bradley, Huahua Du, Naoya Fujita, Gregory H Hockerman, Kevin M Hannon

Publications

INTRODUCTION: We investigated the mechanism by which the MERG1a K+ channel increases ubiquitin proteasome proteolysis (UPP).

METHODS: Hindlimb suspension and electro-transfer of Merg1a cDNA into mouse gastrocnemius muscles induced atrophy.

RESULTS: Atrophic gastrocnemius muscles of hindlimb-suspended mice express Merg1a, Murf1, and Mafbx genes. Electrotransfer of Merg1a significantly decreases muscle fiber size (12.6%) and increases UPP E3 ligase Murf1 mRNA (2.1-fold) and protein (23.7%), but does not affect Mafbx E3 ligase expression. Neither Merg1a-induced decreased fiber size nor Merg1a-induced increased Murf1 expression is curtailed significantly by coexpression of inactive HR-Foxo3a, a gene encoding a transcription factor known to induce Mafbx expression. …

Tachycardia Mediated Cardiomyopathy: Pathophysiology, Mechanisms, Clinical Features And Management., Shuchita Gupta, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Tachycardia mediated cardiomyopathy (TMC) is a reversible form of dilated cardiomyopathy that can occur with most supraventricular and ventricular arrhythmias. Despite the plethora of literature describing this entity in animal models, as well as humans, it remains poorly understood. Over the last decade, new etiologies of TMC, such as frequent premature ventricular complexes in normal hearts, have been identified. Recent advances in catheter-based ablation therapies, particularly for atrial fibrillation and ventricular arrhythmias, have added a new dimension to the treatment of this condition. This review describes the pathophysiology, proposed mechanisms, clinical features and management in various arrhythmic conditions.

Ocean Acidification Impairs Vermetid Reef Recruitment., Marco Milazzo, Riccardo Rodolfo-Metalpa, Vera Bin San Chan, Maoz Fine, Cinzia Alessi, Vengatesen Thiyagarajan, Jason M. Hall-Spencer, Renato Chemello

School of Biological and Marine Sciences

Vermetids form reefs in sub-tropical and warm-temperate waters that protect coasts from erosion, regulate sediment transport and accumulation, serve as carbon sinks and provide habitat for other species. The gastropods that form these reefs brood encapsulated larvae; they are threatened by rapid environmental changes since their ability to disperse is very limited. We used transplant experiments along a natural CO2 gradient to assess ocean acidification effects on the reef-building gastropod Dendropoma petraeum. We found that although D. petraeum were able to reproduce and brood at elevated levels of CO2, recruitment success was adversely affected. Long-term exposure to acidified conditions predicted …

Attention Deficit Associated With Early Life Interictal Spikes In A Rat Model Is Improved With Acth, Amanda E. Hernan, Abigail Alexander, Pierre-Pascal Lenck-Santini, Rod C. Scott

Dartmouth Scholarship

Children with epilepsy often present with pervasive cognitive and behavioral comorbidities including working memory impairments, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder. These non-seizure characteristics are severely detrimental to overall quality of life. Some of these children, particularly those with epilepsies classified as Landau-Kleffner Syndrome or continuous spike and wave during sleep, have infrequent seizure activity but frequent focal epileptiform activity. This frequent epileptiform activity is thought to be detrimental to cognitive development; however, it is also possible that these IIS events initiate pathophysiological pathways in the developing brain that may be independently associated with cognitive deficits. These …

Irf8 Suppresses Pathological Cardiac Remodelling By Inhibiting Calcineurin Signalling., Ding-Sheng Jiang, Xiang Wei, Xiao-Fei Zhang, Yu Liu, Yan Zhang, Ke Chen, Lu Gao, Heng Zhou, Xue-Hai Zhu, Peter P. Liu, Wayne Bond Lau, Xin-Liang Ma, Yunzeng Zou, Xiao-Dong Zhang, Guo-Chang Fan, Hongliang Li

Department of Emergency Medicine Faculty Papers

Interferon regulatory factor 8 (IRF8) is known to affect the innate immune response, for example, by regulating the differentiation and function of immune cells. However, whether IRF8 can influence cardiac hypertrophy is unknown. Here we show that IRF8 levels are decreased in human dilated/hypertrophic cardiomyopathic hearts and in murine hypertrophic hearts. Mice overexpressing Irf8 specifically in the heart are resistant to aortic banding (AB)-induced cardiac hypertrophy, whereas mice lacking IRF8 either globally or specifically in cardiomyocytes develop an aggravated phenotype induced by pressure overload. Mechanistically, we show that IRF8 directly interacts with NFATc1 to prevent NFATc1 translocation and thus inhibits …

Prevention Of Arteriovenous Shunt Occlusion Using Microbubble And Ultrasound Mediated Thromboprophylaxis., Shelby Kutty, Juefei Wu, James M. Hammel, Joseph R. Abraham, Jeeva Venkataraman, Ibrahim Abdullah, David A. Danford, Stanley J. Radio, John Lof, Thomas R. Porter

Journal Articles: Pediatrics

BACKGROUND: Palliative shunts in congenital heart disease patients are vulnerable to thrombotic occlusion. High mechanical index (MI) impulses from a modified diagnostic ultrasound (US) transducer during a systemic microbubble (MB) infusion have been used to dissolve intravascular thrombi without anticoagulation, and we sought to determine whether this technique could be used prophylactically to reduce thrombus burden and prevent occlusion of surgically placed extracardiac shunts.

METHODS AND RESULTS: Heparin-bonded ePTFE tubular vascular shunts of 4 mm×2.5 cm (Propaten; W.L Gore) were surgically placed in 18 pigs: a right-sided side-to-side arteriovenous (AV, carotid-jugular) shunt, and a left-sided arterio-arterial (AA, carotid-carotid) interposition shunt …

Induction Of Autophagy Restores The Loss Of Sevoflurane Cardiac Preconditioning Seen With Prolonged Ischemic Insult., Mayumi Shiomi, Masami Miyamae, Genzou Takemura, Kazuhiro Kaneda, Yoshitaka Inamura, Anna Onishi, Shizuka Koshinuma, Yoshihiro Momota, Toshiaki Minami, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Sevoflurane preconditioning against myocardial ischemia-reperfusion injury is lost if the ischemic insult is too long. Emerging evidence suggests that induction of autophagy may also confer cardioprotection against ischemia-reperfusion injury. We examined whether induction of autophagy prolongs sevoflurane preconditioning protection during a longer ischemic insult. Isolated guinea pigs hearts were subjected to 30 or 45 min ischemia, followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2% sevoflurane for 10 min prior to ischemia (SEVO-30, SEVO-45). Chloramphenicol (autophagy upregulator, 300 µM) was administered starting 20 min before ischemia and throughout reperfusion in SEVO-45 (SEVO-45+CAP). To inhibit autophagy, 3-methyladenine (10 …

Medial Septal Cholinergic Neurons Modulate Isoflurane Anesthesia., Siew Kian Tai, Jingyi Ma, L Stan Leung

Physiology and Pharmacology Publications

BACKGROUND: Cholinergic drugs are known to modulate the response of general anesthesia. However, the sensitivity of isoflurane or other volatile anesthetics after selective lesion of septal cholinergic neurons that project to the hippocampus is not known.

METHODS: Male Long Evans rats had 192 immunoglobulin G-saporin infused into the medial septum (n = 10), in order to selectively lesion cholinergic neurons, whereas control, sham-lesioned rats were infused with saline (n = 12). Two weeks after septal infusion, the hypnotic properties of isoflurane and ketamine were measured using a behavioral endpoint of loss of righting reflex (LORR). Septal lesion was assessed by …

Activation Of Mglur2/3 Receptors In The Ventro-Rostral Prefrontal Cortex Reverses Sensorimotor Gating Deficits Induced By Systemic Nmda Receptor Antagonists., Bridget Valsamis, Michael Chang, Marei Typlt, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Prepulse inhibition (PPI) of acoustic startle is an operational measure of sensorimotor gating, which is disrupted in schizophrenia. NMDA receptor (NMDAR) antagonist induced PPI disruption has become an important pharmacological model for schizophrenia; however, knowledge of the underlying mechanism remains incomplete. This study examines the role of NMDAR in the caudal pontine reticular nucleus (PnC) and the medial prefrontal cortex (mPFC) in NMDARs antagonist induced PPI deficits, as well as the NMDA receptor subtypes involved. We administered the NMDA antagonist MK-801 locally into the caudal pontine reticular formation (PnC), where the PPI mediating pathway converges with the primary startle pathway, …

The Differential Interferon Responses Of Two Strains Of Stat1-Deficient Mice Do Not Alter Susceptibility To Hsv-1 And Vsv In Vivo, Sarah Katzenell, Yufei Chen, Zachary M. Parker, David A. Leib

Dartmouth Scholarship

Stat1 is a pivotal transcription factor for generation of the interferon (IFN)-dependent antiviral response. Two Stat1 knockout mouse lines have been previously generated, one deleted the N-terminal domain (ΔNTD) and one in the DNA-binding domain (ΔDBD). These widely-used strains are assumed interchangeable, and both are highly susceptible to various pathogens. In this study, primary cells derived from ΔNTD mice were shown to be significantly more responsive to IFN, and established an antiviral state with greater efficiency than cells derived from ΔDBD mice, following infection with vesicular stomatitis virus and herpes simplex virus type-1. Also, while mice from both strains succumbed …

Expression Of Mir-15/107 Family Micrornas In Human Tissues And Cultured Rat Brain Cells, Wang-Xia Wang, Robert J. Danaher, Craig S. Miller, Joseph R. Berger, Vega G. Nubia, Bernard R. Wilfred, Janna H. Neltner, Christopher M. Norris, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs), sharing a 5' AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression …

A Novel In Vivo Model For Evaluating Functional Restoration Of A Tissue-Engineered Salivary Gland., Swati Pradhan-Bhatt, Daniel A Harrington, Randall L Duncan, Mary C Farach-Carson, Xinqiao Jia, Robert L Witt

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES/HYPOTHESIS: To create a novel model for development of a tissue-engineered salivary gland from human salivary gland cells that retains progenitor cell markers useful for treatment of radiation-induced xerostomia.

STUDY DESIGN: A three-dimensional (3D) hyaluronic acid (HA)-based hydrogel scaffold was used to encapsulate primary human salivary gland cells and to obtain organized acini-like spheroids. Hydrogels were implanted into rat models, and cell viability and receptor expression were evaluated.

METHODS: A parotid gland surgical resection model for xenografting was developed. Salivary cells loaded in HA hydrogels formed spheroids and in vitro were implanted in the three-fourths resected parotid bed of athymic …

Corticosterone Administration Up-Regulated Expression Of Norepinephrine Transporter And Dopamine Β-Hydroxylase In Rat Locus Coeruleus And Its Terminal Regions, Yan Fan, Ping Ping Chen, Ying Li, Kui Cui, Daniel M. Noel, Elizabeth D. Cummins, Daniel J. Peterson, Russell W. Brown, Meng-Yang Zhu

ETSU Faculty Works

Stress has been reported to activate the locus coeruleus (LC)-noradrenergic system. In this study, corticosterone (CORT) was orally administrated to rats for 21 days to mimic stress status. In situ hybridization measurements showed that CORT ingestion significantly increased mRNA levels of norepinephrine transporter (NET) and dopamine β-hydroxylase (DBH) in the LC region. Immunofluorescence staining and western blotting revealed that CORT treatment also increased protein levels of NET and DBH in the LC, as well as NET protein levels in the hippocampus, the frontal cortex and the amygdala. However, CORT-induced increase in DBH protein levels only appeared in the hippocampus and …

Targeting Fibroblast Activation Protein In Tumor Stroma With Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth And Augment Host Immunity Without Severe Toxicity., Liang-Chuan S. Wang, Albert Lo, John Scholler, Jing Sun, Rajrupa S. Majumdar, Veena Kapoor, Michael Antzis, Cody E. Cotner, Laura A. Johnson, Amy C. Durham, Charalambos C. Solomides, Md, Carl H. June, Ellen Puré, Steven M. Albelda

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAP(hi) stromal cells and inhibited the …