Digital Commons Network^™

Altered Expression Of Alzheimer's Disease-Related Proteins In Male Hypogonadal Mice, Eleanor S. Drummond, Ralph Martins, D J Handelsman, A R Harvey

Research outputs 2012

Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer's disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in lifelong deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and β-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the …

Pegylated Arginine Deiminase Downregulates Colitis In Murine Models, Helieh S. Oz, Jian Zhong, Willem J. S. De Villiers

Physiology Faculty Publications

Arginine deiminase (ADI), an arginine-metabolizing enzyme involved in cell signaling, is dysregulated in multiple inflammatory diseases and cancers. We hypothesized that pegylated ADI (ADI-PEG) provide protection against colitis.

METHODS: Dextran sodium sulfate colitis was induced in IL-10-deficient and BALB/c (WT) mice. ADI-PEG was administered i.p., and inflammatory mediators and pathology were evaluated.

RESULTS: Acute colitis in mice was manifested by increases in inflammatory biomarkers, such as serum amyloid A (SAA, P < 0.001), IL-12 p40, and disease index (3-Fold). In contrast, ADI-PEG significantly decreased clinical disease index, SAA levels, and inflammatory cytokines in blood as well as in colonic explants. Animals developed moderate (2.2 ± 0.3 WT) to severe (3.6 ± 0.5 IL-10 deficient) colonic pathology; and ADI-PEG treatment significantly improved the severity of colitis (P < 0.05). Marked infiltration of CD68+ macrophages and iNOS expression were detected in colonic submucosa in colitic animals but not detected in ADI-PEG-treated animals.

CONCLUSION: ADI-PEG attenuated inflammatory responses by suppression of macrophage infiltration and iNOS expression in colitic animals. ADI-PEG can serve as a potential therapeutic value in IBD.

Cardioprotection Of Controlled And Cardiac-Specific Over-Expression Of A(2a)-Adenosine Receptor In The Pressure Overload., Eman A Hamad, Weizhong Zhu, Tung O Chan, Valerie Myers, Erhe Gao, Xue Li, Jin Zhang, Jianliang Song, Xue-Qian Zhang, Joseph Y Cheung, Walter Koch, Arthur M Feldman

Center for Translational Medicine Faculty Papers

Adenosine binds to three G protein-coupled receptors (R) located on the cardiomyocyte (A(1)-R, A(2A)-R and A(3)-R) and provides cardiac protection during both ischemic and load-induced stress. While the role of adenosine receptor-subtypes has been well defined in the setting of ischemia-reperfusion, far less is known regarding their roles in protecting the heart during other forms of cardiac stress. Because of its ability to increase cardiac contractility and heart rate, we hypothesized that enhanced signaling through A(2A)-R would protect the heart during the stress of transverse aortic constriction (TAC). Using a cardiac-specific and inducible promoter, we selectively over-expressed A(2A)-R in FVB …

Substance P And The Host Immune Response, Megan Elizabeth Foldenauer

Wayne State University Dissertations

This body of work examined the mechanism by which SP regulates host immunity, specifically, its control of growth factors and TLR expression in the P. aeruginosa-infected cornea. The role of mTOR and VIP in corneal infection and inflammation also was tested.

SP has a dual role in bacterial infection, unexpectedly upregulating growth factor production. This was accompanied by macrophage-specific upregulation of pro-inflammatory cytokines, downregulation of anti-inflammatory cytokines, and upregulation of anti-apoptotic genes, as well as a decrease in arginase-producing macrophages (M2 cells), important in stromal healing in these mice. All of these lead to worsened disease, despite the stimulatory effects …

Evaluation Of Protection In A Mouse Model After Vaccination With Mycobacterium Avium Subsp. Paratuberculois Protein Cocktails, J.R. Stabel, A. Barnhill, J. P. Bannantine, Y.F. Chang, M.A. Osman

United States Department of Agriculture-Agricultural Research Service / University of Nebraska-Lincoln: Faculty Publications

Whole-cell vaccines successfully reduce signs of clinical disease and fecal shedding of Mycobacterium avium subsp. paratuberculosis (MAP), however, these vaccines have some limitations. The present study was conducted to identify MAP proteins that might be candidates for the development of an improved vaccine. MAP proteins were screened for immunogenicity in naturally infected cattle and selected based upon reactivity in the interferon-􏰀 (IFN-􏰀) and Western blot assays. Proteins (MAP1087, MAP1204, MAP1272c, and MAP2077c) were arrayed into 4 overlapping cocktails containing 3 proteins each. The efficacy of the proteins within these cocktails as vaccine candidates was evaluated by subcutaneous immunization of mice, …

Rituximab Therapy In Pulmonary Alveolar Proteinosis Improves Alveolar Macrophage Lipid Homeostasis., Anagha Malur, Mani Kavuru, Irene Marshall, Barbara P Barna, Isham Huizar, Reema Karnekar, Mary Jane Thomassen

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

RATIONALE: Pulmonary Alveolar Proteinosis (PAP) patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF) attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and the PPARγ-regulated ATP binding cassette (ABC) lipid transporter, ABCG1. An open label proof of concept Phase II clinical trial was conducted in PAP patients using rituximab, a chimeric murine-human monoclonal antibody directed against B lymphocyte specific antigen CD20. Rituximab treatment decreased anti-GM-CSF antibody levels in bronchoalveolar lavage (BAL) fluid, and 7/9 patients …

A Study Of The Genetic Mechanisms Used To Regulate The Third Complementarity Determining Region Of The Immunoglobulin H Chain, Mohamed Khass

All ETDs from UAB

Developing B cells exhibit sequential changes in the representation of immunoglobulin (Ig) heavy (H) chain sequences with excess hydrophobic or charged amino acids in complementarity determining region 3 (CDR-H3). To begin to elucidate the mechanisms by which this process occurs, we used Bromodeoxy Uridine (BrdU) incorporation and Annexin V binding to quantify B cell turnover and cell cycle progression in developing B cell subsets in the bone marrow, spleen and peritoneal cavity of wild-type BALB/c mice. To magnify the effects of hydrophobicity and charge, we included in this analysis mice limited to the use of an IgH allele with a …

Testosterone Treatment Fails To Accelerate Disease In A Transgenic Mouse Model Of Spinal And Bulbar Muscular Atrophy., Erica S Chevalier-Larsen, Diane E Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Evidence from multiple animal models demonstrates that testosterone plays a crucial role in the progression of symptoms in spinal and bulbar muscular atrophy (SBMA), a condition that results in neurodegeneration and muscle atrophy in affected men. Mice bearing a transgene encoding a human androgen receptor (AR) that contains a stretch of 112 glutamines (expanded polyglutamine tract; AR112Q mice) reproduce several aspects of the human disease. We treated transgenic male AR112Q mice with testosterone for 6 months. Surprisingly, testosterone treatment of AR112Q males did not exacerbate the disease. Although transgenic AR112Q males exhibited functional deficits when compared with non-transgenics, long-term testosterone …

Scd1 Plays A Tumor-Suppressive Role In Survival Of Leukemia Stem Cells And The Development Of Chronic Myeloid Leukemia, H Zhang, H Li, N Ho, Dongguang Li, Shaoguang Li

Research outputs 2012

Chronic myeloid leukemia (CML) is derived from a stem cell, and it is widely accepted that the existence of leukemia stem cells (LSCs) is one of the major reasons for the relapse of CML treated with kinase inhibitors. Key to eradicating LSCs is to identify genes that play a critical role in survival regulation of these stem cells. Using BCR-ABL-induced CML mouse model, here we show that expression of the stearoyl-CoA desaturase 1 (Scd1) gene is downregulated in LSCs and that Scd1 plays a tumor-suppressive role in LSCs with no effect on the function of normal hematopoietic stem cells. Deletion …

The Dermatan Sulfate Proteoglycan Decorin Modulates Α2Β1 Integrin And The Vimentin Intermediate Filament System During Collagen Synthesis., Oliver Jungmann, Katerina Nikolovska, Christian Stock, Jan-Niklas Schulz, Beate Eckes, Christoph Riethmüller, Rick T Owens, Renato V Iozzo, Daniela G Seidler

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(-/-)) mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(-/-) mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(-/-) fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, …

Decorin Protein Core Affects The Global Gene Expression Profile Of The Tumor Microenvironment In A Triple-Negative Orthotopic Breast Carcinoma Xenograft Model., Simone Buraschi, Thomas Neill, Rick T Owens, Leonardo A Iniguez, George Purkins, Rajanikanth Vadigepalli, Barry Evans, Liliana Schaefer, Stephen C Peiper, Zi-Xuan Wang, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found that …

Gentamicin Rapidly Inhibits Mitochondrial Metabolism In High-Frequency Cochlear Outer Hair Cells, Heather Jensen Smith, Richard Hallworth, Michael G. Nichols

Journal Articles: Eppley Institute

Aminoglycosides (AG), including gentamicin (GM), are the most frequently used antibiotics in the world and are proposed to cause irreversible cochlear damage and hearing loss (HL) in 1/4 of the patients receiving these life-saving drugs. Akin to the results of AG ototoxicity studies, high-frequency, basal turn outer hair cells (OHCs) preferentially succumb to multiple HL pathologies while inner hair cells (IHCs) are much more resilient. To determine if endogenous differences in IHC and OHC mitochondrial metabolism dictate differential sensitivities to AG-induced HL, IHC- and OHC-specific changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH) fluorescence during acute (1 h) GM treatment …

Methamphetamine Administration Targets Multiple Immune Subsets And Induces Phenotypic Alterations Suggestive Of Immunosuppression., Robert Z. Harms, Brenda M. Morsey, Craig W. Boyer, Howard S. Fox, Nora E. Sarvetnick

Journal Articles: Regenerative Medicine

Methamphetamine (Meth) is a widely abused stimulant and its users are at increased risk for multiple infectious diseases. To determine the impact of meth on the immune system, we utilized a murine model that simulates the process of meth consumption in a typical addict. Our phenotypic analysis of leukocytes from this dose escalation model revealed that meth affected key immune subsets. Meth administration led to a decrease in abundance of natural killer (NK) cells and the remaining NK cells possessed a phenotype suggesting reduced responsiveness. Dendritic cells (DCs) and Gr-1(high) monocytes/macrophages were also decreased in abundance while Gr-1(low) monocytes/macrophages appear …

Cellular Retrograde Cardiomyoplasty And Relaxin Therapy For Postischemic Myocardial Repair In A Rat Model, Gabriella Di Lascio, Guy Harmelin, Mattia Targetti, Cristina Nanni, Giacomo Bianchi, Tommaso Gasbarri, Sandro Gelsomino, Daniele Bani, Sandra Zecchi Orlandini, Massimo Bonacchi

The Texas Heart Institute Journal

We sought to determine whether skeletal myoblasts, wild-type or engineered to express relaxin, might improve myocardial viability and performance in a rat model of chronic myocardial infarction. Our purpose was to investigate a potential new therapy for heart failure.

From October 2005 through September 2009, we surgically induced acute myocardial infarction in 80 male Wistar rats. Thirty days after surgery, the rats underwent reoperation for the retrograde coronary venous infusion of skeletal myoblasts, relaxin, or both. The animals were randomly assigned to 4 experimental groups: R1 (the control group, which underwent saline-solution infusion), R2 (systemic relaxin therapy), R3 (myoblast infusion), …

Administration Of Bone Marrow Derived Mesenchymal Stem Cells Into The Liver: Potential To Rescue Pseudoxanthoma Elasticum In A Mouse Model (Abcc6-/-)., Qiujie Jiang, Shunsuke Takahagi, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE) is a heritable ectopic mineralization disorder caused by loss-of-function mutations in the ABCC6 gene which is primarily expressed in the liver. There is currently no effective treatment for PXE. In this study, we characterized bone marrow derived mesenchymal stem cells (MSCs) and evaluated their ability to contribute to liver regeneration, with the aim to rescue PXE phenotype. The MSCs, isolated from GFP-transgenic mice by magnetic cell sorting, were shown to have high potential for hepatic differentiation, with expression of Abcc6, in culture. These cells were transplanted into the livers of 4-week-old immunodeficient Abcc6⁻/⁻ mice by intrasplenic injection …

Cd2ap Regulates Sumoylation Of Cin85 In Podocytes, Irini Tossidou, Rainer Niedenthal, Malte Klaus, Beina Teng, Kirstin Worthmann, Benjamin King, Kevin Peterson

Dartmouth Scholarship

Podocytes are highly differentiated and polarized epithelial cells located on the visceral side of the glomerulus. They form an indispensable component of the glomerular filter, the slit diaphragm, formed by several transmembrane proteins and adaptor molecules. Disruption of the slit diaphragm can lead to massive proteinuria and nephrotic syndrome in mice and humans. CD2AP is an adaptor protein that is important for the maintenance of the slit diaphragm. Together with its paralogue, CIN85, CD2AP belongs to a family of adaptor proteins that are primarily described as being involved in endocytosis and downregulation of receptor tyrosine kinase activity. We have shown …

A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional …

Microglial P38Α Mapk Is Critical For Lps-Induced Neuron Degeneration, Through A Mechanism Involving Tnfα, Bin Xing, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The p38α MAPK isoform is a well-established therapeutic target in peripheral inflammatory diseases, but the importance of this kinase in pathological microglial activation and detrimental inflammation in CNS disorders is less well understood. To test the role of the p38α MAPK isoform in microglia-dependent neuron damage, we used primary microglia from wild-type (WT) or p38α MAPK conditional knockout (KO) mice in co-culture with WT cortical neurons, and measured neuron damage after LPS insult.

RESULTS: We found that neurons in co-culture with p38α-deficient microglia were protected against LPS-induced synaptic loss, neurite degeneration, and neuronal death. The involvement of the proinflammatory …

Triterpenoid Modulation Of Il-17 And Nrf-2 Expression Ameliorates Neuroinflammation And Promotes Remyelination In Autoimmune Encephalomyelitis, Tej K. Pareek, Abdelmadjid Belkadi, Sashi Kesavapany, Anita Zaremba, Sook L. Loh, Lianhua Bai, Mark L. Cohen, Colin Meyer, Karen T. Liby, Robert H. Miller, Michael B. Sporn, John J. Letterio

Dartmouth Scholarship

Inflammatory cytokines and endogenous anti-oxidants are variables affecting disease progression in multiple sclerosis (MS). Here we demonstrate the dual capacity of triterpenoids to simultaneously repress production of IL-17 and other pro-inflammatory mediators while exerting neuroprotective effects directly through Nrf2-dependent induction of anti-oxidant genes. Derivatives of the natural triterpene oleanolic acid, namely CDDO-trifluoroethyl-amide (CDDO-TFEA), completely suppressed disease in a murine model of MS, experimental autoimmune encephalomyelitis (EAE), by inhibiting Th1 and Th17 mRNA and cytokine production. Encephalitogenic T cells recovered from treated mice were hypo-responsive to myelin antigen and failed to adoptively transfer the disease. Microarray analyses showed significant suppression of …

Wnt Signaling Exerts An Antiproliferative Effect On Adult Cardiac Progenitor Cells Through Igfbp3., Angelos Oikonomopoulos, Konstantina-Ioanna Sereti, Frank Conyers, Michael Bauer, Annette Liao, Jian Guan, Dylan Crapps, Jung-Kyu Han, Hanhua Dong, Ahmad F Bayomy, Gabriel C Fine, Karen Westerman, Travis L Biechele, Randall T Moon, Thomas Force, Ronglih Liao

Center for Translational Medicine Faculty Papers

RATIONALE: Recent work in animal models and humans has demonstrated the presence of organ-specific progenitor cells required for the regenerative capacity of the adult heart. In response to tissue injury, progenitor cells differentiate into specialized cells, while their numbers are maintained through mechanisms of self-renewal. The molecular cues that dictate the self-renewal of adult progenitor cells in the heart, however, remain unclear.

OBJECTIVE: We investigate the role of canonical Wnt signaling on adult cardiac side population (CSP) cells under physiological and disease conditions.

METHODS AND RESULTS: CSP cells isolated from C57BL/6J mice were used to study the effects of canonical …

Functional Genomics Reveals An Essential And Specific Role For Stat1 In Protection Of The Central Nervous System Following Herpes Simplex Virus Corneal Infection, Tracy J. Pasieka, Cristian Cilloniz, Victoria S. Carter, Pamela Rosato, Michael G. Katze, David A. Leib

Dartmouth Scholarship

Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), …

Effect Of Voluntary Exercise And Diet On The Unfolded Protein Response In The Brain Of Mice, Yu Ho Kim

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The medical costs for many chronic diseases are increasing dramatically and placing a major financial burden on nations and individuals in both developed and developing countries. A number of chronic diseases, such as obesity, type 2 diabetes and some neurodegenerative diseases are all attenuated by a history of physical activity suggesting that they may be interconnected in some way. It has been suggested that cellular stress is a major factor promoting these chronic diseases.

Cellular stress occurs in a specific compartment within the cell, the endoplasmic reticulum, whose normal function is in the synthesis and folding of proteins into the …

B1b Lymphocyte-Derived Antibodies Control Borrelia Hermsii Independent Of Fcα/Μ Receptor And In The Absence Of Host Cell Contact., Matthew J. Colombo, David Abraham, Akira Shibuya, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

The critical role of IgM in controlling pathogen burden has been demonstrated in a variety of infection models. In the murine model of Borrelia hermsii infection, IgM is necessary and sufficient for the rapid clearance of bacteremia. Convalescent, but not naïve, B1b cells generate a specific IgM response against B. hermsii, but the mechanism of IgM-mediated protection is unknown. Here, we show that neither Fcα/μR, a high-affinity receptor for IgM, nor IgM-dependent complement activation is required for controlling B. hermsii. Bacteria in diffusion chambers with a pore size impermeable to cells were killed when diffusion chambers were implanted into either …

Acute And Chronic Toxicity Of Moringa Oleifera Linn Leaves Extracts, Songpol Chivapat, Pornchai Sincharoenpokai, Nalinphat Saktiyasuthorn, Aussavachai Shuaprom, Pratom Thongsrirak, Apirak Sakpetch, Anudep Rungsipipat

The Thai Journal of Veterinary Medicine

Moringa oleifera leaves have been reported to possess potential hypotensive and hypocholesterolemic andhypoglycemic activities; nevertheless toxicological data of this herb in animal models have still been scanty. Theobjective of this study was to evaluate both acute and chronic toxicity of the water extract of M. oleifera leaves by oraladministration. Acute toxicity test in mice by gavage with the extract twice, each at the dose of 10 g/kg, revealed thatthe extract produced no acute toxic symptoms and gross lesions of vital organs. Chronic toxicity study wasinvestigated in eighty Wistar rats allocated into four groups, each of ten per sex. Group 1 …

Paradoxical Reversal Learning Enhancement By Stress Or Prefrontal Cortical Damage: Rescue With Bdnf., Carolyn Graybeal, Michael Feyder, Emily Schulman, Lisa M Saksida, Timothy J Bussey, Jonathan L Brigman, Andrew Holmes

Brain and Mind Institute Researchers' Publications

Stress affects various forms of cognition. We found that moderate stress enhanced late reversal learning in a mouse touchscreen-based choice task. Ventromedial prefrontal cortex (vmPFC) lesions mimicked the effect of stress, whereas orbitofrontal and dorsolateral striatal lesions impaired reversal. Stress facilitation of reversal was prevented by BDNF infusion into the vmPFC. These findings suggest a mechanism by which stress-induced vmPFC dysfunction disinhibits learning by alternate (for example, striatal) systems.

Culture Medium, Gas Atmosphere And Mapk Inhibition Affect Regulation Of Rna-Binding Protein Targets During Mouse Preimplantation Development., Michele D Calder, Patricia H Watson, Andrew J Watson

Obstetrics & Gynaecology Publications

During oogenesis, mammalian oocytes accumulate maternal mRNAs that support the embryo until embryonic genome activation. RNA-binding proteins (RBP) may regulate the stability and turnover of maternal and embryonic mRNAs. We hypothesised that varying embryo culture conditions, such as culture medium, oxygen tension and MAPK inhibition, affects regulation of RBPs and their targets during preimplantation development. STAU1, ELAVL1, KHSRP and ZFP36 proteins and mRNAs were detected throughout mouse preimplantation development, whereas Elavl2 mRNA decreased after the two-cell stage. Potential target mRNAs of RBP regulation, Gclc, Slc2a1 and Slc7a1 were detected during mouse preimplantation development. Gclc mRNA was significantly elevated in embryos …

An Engineered Approach To Stem Cell Culture: Automating The Decision Process For Real-Time Adaptive Subculture Of Stem Cells, Dai Fei Elmer Ker, Lee E. Weiss, Silvina N. Junkers, Mei Chen, Zhaozheng Yin, Mike F. Sandbothe, Seungil Huh, Sungeun Eom, Ryoma Bise, Elvira Osuna-Highley, Takeo Kanade, Phil Gordon Campbell

Computer Science Faculty Research & Creative Works

Current cell culture practices are dependent upon human operators and remain laborious and highly subjective, resulting in large variations and inconsistent outcomes, especially when using visual assessments of cell confluency to determine the appropriate time to subculture cells. Although efforts to automate cell culture with robotic systems are underway, the majority of such systems still require human intervention to determine when to subculture. Thus, it is necessary to accurately and objectively determine the appropriate time for cell passaging. Optimal stem cell culturing that maintains cell pluripotency while maximizing cell yields will be especially important for efficient, cost-effective stem cell-based therapies. …

Early Exposure To Paraquat Sensitizes Dopaminergic Neurons To Subsequent Silencing Of Pink1 Gene Expression In Mice., Hongxia Zhou, Cao Huang, Jianbin Tong, Xugang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Environmental exposure, genetic modification, and aging are considered risky for Parkinson's disease (PD). How these risk factors cooperate to induce progressive neurodegeneration in PD remains largely unknown. Paraquat is an herbicide commonly used for weed and grass control. Exposure to paraquat is associated with the increased incidence of PD. In contrast to familial PD, most sporadic PD cases do not have genetic mutation, but may suffer from partial dysfunction of neuron-protective genes as aging. Using conditional transgenic RNAi, we showed that temporal silencing of PINK1 expression in adult mice increased striatal dopamine, the phenotype that could not be induced by …

Reversal Of Glial And Neurovascular Markers Of Unhealthy Brain Aging By Exercise In Middle-Aged Female Mice, Caitlin S. Latimer, James L. Searcy, Michael T. Bridges, Lawrence D. Brewer, Jelena Popović, Eric M. Blalock, Philip W. Landfield, Olivier Thibault, Nada M. Porter

Pharmacology and Nutritional Sciences Faculty Publications

Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for …

Thrombospondin1 Deficiency Reduces Obesity-Associated Inflammation And Improves Insulin Sensitivity In A Diet-Induced Obese Mouse Model, Yanzhang Li, Xiaopeng Tong, Courtney Rumala, Kate Clemons, Shuxia Wang

Graduate Center for Nutritional Sciences Faculty Publications

BACKGROUND: Obesity is prevalent worldwide and is associated with insulin resistance. Advanced studies suggest that obesity-associated low-grade chronic inflammation contributes to the development of insulin resistance and other metabolic complications. Thrombospondin 1 (TSP1) is a multifunctional extracellular matrix protein that is up-regulated in inflamed adipose tissue. A recent study suggests a positive correlation of TSP1 with obesity, adipose inflammation, and insulin resistance. However, the direct effect of TSP1 on obesity and insulin resistance is not known. Therefore, we investigated the role of TSP1 in mediating obesity-associated inflammation and insulin resistance by using TSP1 knockout mice.

METHODOLOGY/PRINCIPAL FINDINGS: Male TSP1-/- mice …