Digital Commons Network^™

Time Of Day Regulates Subcellular Trafficking, Tripartite Synaptic Localization, And Polyadenylation Of The Astrocytic Fabp7 Mrna, Jason R. Gerstner, William M. Vanderheyden, Timothy Lavaute, Cara J. Westmark, Labib Rouhana, Allan I. Pack, Marvin Wickens, Charles F. Landry

Biological Sciences Faculty Publications

The astrocyte brain fatty acid binding protein (Fabp7) has previously been shown to have a coordinated diurnal regulation of mRNA and protein throughout mouse brain, and an age-dependent decline in protein expression within synaptoneurosomal fractions. Mechanisms that control time-of-day changes in expression and trafficking Fabp7 to the perisynaptic process are not known. In this study, we confirmed an enrichment of Fabp7 mRNA and protein in the astrocytic perisynaptic compartment, and observed a diurnal change in the intracellular distribution of Fabp7 mRNA in molecular layers of hippocampus. Northern blotting revealed a coordinated time-of-day-dependent oscillation for the Fabp7 mRNA poly(A) tail throughout …

The Effects Of Oxygen On The Electrophysiology Of Co2/H+-Chemosensitive And -Insensitive Neurons Of The Solitary Complex Of The Rat, Michael Patrick Matott

USF Tampa Graduate Theses and Dissertations

This study tested the hypothesis that decreasing the control O₂ level from 95% to 40% (5% CO₂ + 55% N₂) maintains viability in caudal solitary complex (cSC) neurons in transverse slices (~300-400ꝳ) prepared from neonatal rat (P2-22) maintained at 32-34°C. The underlying rationale is to reduce exposure to redox and nitrosative stimuli generated during several hours of exposure to 95% O₂ that produces a tissue O₂ tension throughout the slice which is in excess of 203 kPa (2.0 atmospheres absolute,ATA) oxygen. Whole cell recordings of cSC neurons maintained in 40% O₂ exhibited spontaneous …

Phase I Evaluation Of Intravenous Ascorbic Acid In Combination With Gemcitabine And Erlotinib In Patients With Metastatic Pancreatic Cancer., Daniel A. Monti, Md, Edith Mitchell, Anthony J Bazzan, Susan Littman, George Zabrecky, Charles J Yeo, Madhaven V Pillai, Andrew B Newberg, Sandeep Deshmukh, Mark Levine

Department of Medical Oncology Faculty Papers

BACKGROUND: Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.

METHODS AND FINDINGS: 14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of …

Uterine Dysfunction In Biglycan And Decorin Deficient Mice Leads To Dystocia During Parturition., Zhiping Wu, Abraham W Aron, Elyse E Macksoud, Renato V Iozzo, Chi-Ming Hai, Beatrice E Lechner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cesarean birth rates are rising. Uterine dysfunction, the exact mechanism of which is unknown, is a common indication for Cesarean delivery. Biglycan and decorin are two small leucine-rich proteoglycans expressed in the extracellular matrix of reproductive tissues and muscle. Mice deficient in biglycan display a mild muscular dystrophy, and, along with mice deficient in decorin, are models of Ehlers-Danlos Syndrome, a connective tissue anomaly associated with uterine rupture. As a variant of Ehlers-Danlos Syndrome is caused by a genetic mutation resulting in abnormal biglycan and decorin secretion, we hypothesized that biglycan and decorin play a role in uterine function. Thus, …

Synthetic Peptides Derived From The Sequence Of A Lasso Peptide Microcin J25 Show Antibacterial Activity, Rania Soudy, Liru Wang, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Microcin J25 (MccJ25) is a plasmid-encoded, ribosomally synthesized antibacterial peptide with a unique lasso structure. The lasso structure, produced with the aid of two processing enzymes, provides exceptional stability to MccJ25. We report the synthesis of six peptides (1–6), derived from the MccJ25 sequence, that are designed to form folded conformation by disulfide bond formation and electrostatic or hydrophobic interactions. Two peptides (1 and 6) display good activity against Salmonella newport, and are the first synthetic derivatives of MccJ25 that are bactericidal. Peptide 1 displays potent activity against several Salmonella strains including two …

Nanomaterials And Cellular Interaction In The Nervous System, Caleb Joseph Pingel

Student Theses and Dissertations

Nanoparticles (NPs), materials fabricated in nanosize, are being increasingly used due to their unique applications. The potential risks from inhaling NPs and the interaction of inhaled NPs with the peripheral nervous system in rat were determined in this study by investigating 1) retrograde transport of inhaled NP's to the Nodose Ganglion (NDG) neurons, 2) NDG neuronal interaction with NPs in vitro, and 3) the fluid kinetics of NPs in cell sustaining media. Intratracheal intubation and instilling fluorescent NPs with and without a tracer dye (SP-DiOC) showed that NPS were transported from nerve endings in airway to neurons. Exposing NDG neurons …

Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan-Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay

Pharmacology and Toxicology Publications

Aims and Hypothesis

Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.

Methods

Gem-deficient mice were generated and their metabolic phenotype characterised by …

Localization And Sub-Cellular Shuttling Of Htlv-1 Tax With The Mirna Machinery, Rachel Van Duyne, Irene Guendel, Zachary Klase, Aarthi Narayanan, William Coley, Elizabeth Jaworski, Jessica Roman, Anastas Popratiloff, Renaud Mahieux, Kylene Kehn-Hall, Fatah Kashanchi

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in …

Lipid Environment Modulates The Development Of Acute Tolerance To Ethanol In Caenorhabditis Elegans, Jill C. Bettinger, Kapo Leung, Mia H. Bolling, Andrew D. Goldsmith, Andrew G. Davies

Pharmacology and Toxicology Publications

The development of tolerance to a drug at the level of the neuron reflects a homeostatic mechanism by which neurons respond to perturbations of their function by external stimuli. Acute functional tolerance (AFT) to ethanol is a fast compensatory response that develops within a single drug session and normalizes neuronal function despite the continued presence of the drug. We performed a genetic screen to identify genes required for the development of acute functional tolerance to ethanol in the nematode C. elegans. We identified mutations affecting multiple genes in a genetic pathway known to regulate levels of triacylglycerols (TAGs) via …

Morphine Decreases Enteric Neuron Excitability Via Inhibition Of Sodium Channels, Tricia H. Smith, John R. Grider, William L. Dewey, Hamid I. Akbarali

Pharmacology and Toxicology Publications

Gastrointestinal peristalsis is significantly dependent on the enteric nervous system. Constipation due to reduced peristalsis is a major side-effect of morphine, which limits the chronic usefulness of this excellent pain reliever in man. The ionic basis for the inhibition of enteric neuron excitability by morphine is not well characterized as previous studies have mainly utilized microelectrode recordings from whole mount myenteric plexus preparations in guinea pigs. Here we have developed a Swiss-Webster mouse myenteric neuron culture and examined their electrophysiological properties by patch-clamp techniques and determined the mechanism for morphine-induced decrease in neuronal excitability. Isolated neurons in culture were confirmed …

A First-Generation Multi-Functional Cytokine For Simultaneous Optical Tracking And Tumor Therapy, Shawn Hingtgen, Randa Kasmieh, Elizabeth Elbayly, Irina Nesterenko, Jose-Luiz Figueiredo, Rupesh Dash, Devanand Sarkar, David Hall, Dima Kozakov, Sandor Vajda, Paul B. Fisher, Khalid Shah

Human and Molecular Genetics Publications

Creating new molecules that simultaneously enhance tumor cell killing and permit diagnostic tracking is vital to overcoming the limitations rendering current therapeutic regimens for terminal cancers ineffective. Accordingly, we investigated the efficacy of an innovative new multi-functional targeted anti-cancer molecule, SM7L, using models of the lethal brain tumor Glioblastoma multiforme (GBM). Designed using predictive computer modeling, SM7L incorporates the therapeutic activity of the promising anti-tumor cytokine MDA-7/IL-24, an enhanced secretory domain, and diagnostic domain for non-invasive tracking. In vitro assays revealed the diagnostic domain of SM7L produced robust photon emission, while the therapeutic domain showed marked anti-tumor efficacy and significant …

The Adjuvanticity Of An O. Volvulus-Derived Rov-Asp-1 Protein In Mice Using Sequential Vaccinations And In Non-Human Primates, Jing Wang, Nancy Trichoche, Lanying Du, Meredith Hunter, Bin Zhan, Gaddam Goud, Elizabeth S. Didier, Jing Liu, Lu Lu, Preston A. Marx, Shibo Jiang, Sara Lustigman

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulusrecombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the r …

Chhs January 2012 E-Newsletter, Dr. John Bonaguro, Dean, Vashon S. Wells, Editor, Wku College Of Health & Human Services

College of Health & Human Services Publications

No abstract provided.

Nuclear Receptor Expression And Characterization Of The Major Retinoic Acid Target Gene In Melanoma, Linda L. Eastham

Theses, Dissertations and Capstones

Malignant melanoma is the primary cause of death from all diseases arising from the skin and it is one of the most resistant tumors to standard treatment options. The increasing incidence of melanoma and its poor prognosis makes the understanding of melanoma cell biology very important. Melanoma progression is a complex, multi-step process, and the molecular events leading to melanoma tumor cell proliferation and invasion still need further examination. This study is focused on measuring the expression and activity of two specific genes and their protein counterparts that are altered during melanoma progression. It also examines the mechanism through which …

Loss Of Renal Allografts Secondary To Candida Vascular Complications In Two Recipients From The Same Donor, Govardhana R. Yannam, Lucile E. Wrenshall, R. Brian Stevens

Neuroscience, Cell Biology & Physiology Faculty Publications

Infections remain a major cause of morbidity and mortality in transplant patients. Organ recipients are also susceptible to donor-derived pathogens and the majority of donor infections are easily treatable. Rarely, some pathogens have produced life-threatening complications by compromising the vascular anastomosis. In this case series we report loss of two kidney allografts secondary to vascular complications due to Candida albicans. Both recipients received grafts from a common donor, in whom Candida bacteremia in the donor was not apparent at the time of organ acceptance but became apparent on delayed cultures.

Acid Sphingomyelinase Gene Knockout Ameliorates Hyperhomocysteinemic Glomerular Injury In Mice Lacking Cystathionine-Β-Synthase, Krishna M. Boini, Min Xia, Justine M. Abais, Ming Xu, Cai-Xia Li, Pin-Lan Li

Pharmacology and Toxicology Publications

Acid sphingomyelinase (ASM) has been implicated in the development of hyperhomocysteinemia (hHcys)-induced glomerular oxidative stress and injury. However, it remains unknown whether genetically engineering of ASM gene produces beneficial or detrimental action on hHcys-induced glomerular injury. The present study generated and characterized the mice lacking cystathionine β-synthase (Cbs) and Asm mouse gene by cross breeding Cbs+/− and Asm+/− mice. Given that the homozygotes of Cbs−/−/Asm−/− mice could not survive for 3 weeks. Cbs+/−/Asm+/+, Cbs+/−/Asm+/− and Cbs+/−/Asm−/− as well as their Cbs wild type littermates were used to study the role of Asm−/− under a background of Cbs+/− with hHcys. HPLC …

New Portable Tool To Screen Vestibular And Visual Function—National Institutes Of Health Toolbox Initiative, Rose Marie Rine, Dale Roberts, Bree A. Corbin, Roberta Mckean-Cowdin, Rohit Varma, Jennifer Beaumont, Jerry Slotkin, Michael C. Schubert

Physical Therapy Faculty Research

As part of the National Institutes of Health Toolbox initiative, we developed a low-cost, easy-to-administer, and time-efficient test of vestibular and visual function. A computerized test of dynamic visual acuity (cDVA) was used to measure the difference in visual acuity between head still and moving in yaw. Participants included 318 individuals, aged 3 to 85 years (301 without and 17 with vestibular pathology). Adults used Early Treatment of Diabetic Retinopathy Study (ETDRS) optotypes; children used ETDRS, Lea, and HOTV optotypes. Bithermal calorics, rotational chair, and light box testing were used to validate the cDVA. Analysis revealed that the cDVA test …

Erlin2 Promotes Breast Cancer Cell Survival By Modulating Endoplasmic Reticulum Stress Pathways, Guohui Wang, Gang Liu, Xiaogang Wang, Seema Sethi, Rouba Ali-Fehmi, Judith Abrams, Ze Zheng, Kezhong Zhang, Stephen Ethier, Zeng-Quan Yang

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Amplification of the 8p11-12 region has been found in approximately 15% of human breast cancer and is associated with poor prognosis. Previous genomic analysis has led us to identify the endoplasmic reticulum (ER) lipid raft-associated 2 (ERLIN2) gene as one of the candidate oncogenes within the 8p11-12 amplicon in human breast cancer, particularly in the luminal subtype. ERLIN2, an ER membrane protein, has recently been identified as a novel mediator of ER-associated degradation. Yet, the biological roles of ERLIN2 and molecular mechanisms by which ERLIN2 coordinates ER pathways in breast carcinogenesis remain unclear.

Methods

We established the MCF10A-ERLIN2 …

Vascular Inflammatory Cells In Hypertension., David G Harrison, Paul J. Marvar, Jens M Titze

Pharmacology and Physiology Faculty Publications

Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients, and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. …

Keratinocyte-Targeted Expression Of Human Laminin Γ2 Rescues Skin Blistering And Early Lethality Of Laminin Γ2 Deficient Mice., Tracy L Adair-Kirk, Gail L Griffin, Michelle J Meyer, Diane G Kelley, Jeffrey H Miner, Douglas R Keene, M Peter Marinkovich, J Michael Ruppert, Jouni Uitto, Robert M Senior

Department of Dermatology and Cutaneous Biology Faculty Papers

Laminin-332 is a heterotrimeric basement membrane component comprised of the α3, ß3, and γ2 laminin chains. Laminin-332 modulates epithelial cell processes, such as adhesion, migration, and differentiation and is prominent in many embryonic and adult tissues. In skin, laminin-332 is secreted by keratinocytes and is a key component of hemidesmosomes connecting the keratinocytes to the underlying dermis. In mice, lack of expression of any of the three Laminin-332 chains result in impaired anchorage and detachment of the epidermis, similar to that seen in human junctional epidermolysis bullosa, and death occurs within a few days after birth. To bypass the early …

Statin-Mediated Attenuation Of Chemokine Expression In Peripheral Nerve Vascular Endothelial Cells, Kelly Ann Langert

Dissertations

Pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), play a pivotal role in the pathogenesis of Guillain-Barré Syndrome (GBS), a debilitating autoimmune disorder that affects the peripheral nervous system. By up-regulating endothelial expression of chemokines and cell adhesion molecules (CAMs), TNF-α facilitates the recruitment and trafficking of autoreactive leukocytes across the blood-nerve barrier and into peripheral nerves, an early pathological hallmark of GBS. Literature indicates that TNF-α, monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) are locally increased in patients with GBS, correlating with disease severity. Similar findings have been demonstrated in an animal model of GBS, experimental autoimmune neuritis …

The Effects Of Smooth Muscle Cells On Engineered Microvasculatures In Fibrin Hydrogels, Areck A. Ucuzian

Dissertations

Capillaries are comprised of two cell types: the endothelial cells (ECs) which line the lumen of the capillary, and the supporting pericytes which are closely apposed to the abluminal surface of the capillary wall (sometimes called mural cells). These pericytes are phenotypic derivations of mesenchymal organ stromal cells (from smooth muscle cells and fibroblasts in blood vessels, for example), are recruited and incorporate into the neocapillaries, and are known to mediate reciprocal interactions with ECs during angiogenesis. The overall purpose of this project is to determine how smooth muscle cells (SMCs) affect angiogenesis during microvascular development in fibrin hydrogels using …

Effects Of Adipocyte Deficiency Of Angiotensin Type 1a Receptors In Models Of Obesity And Hypercholesterolemia, Kelly Anne Putnam

Theses and Dissertations--Nutritional Sciences

Adipocytes express angiotensin II (AngII) receptors; however the direct effects of AngII at the adipocyte remain unclear. Knockout mouse models of renin-angiotensin system components exhibit reduced body weight, reduced adiposity, improved glucose tolerance, and improved blood pressure when fed high fat diets, which may be due to reduced action of AngII through the AT1aR in adipocytes. Additionally, hypercholesterolemic AT1aR deficient mice are protected from AngII-induced increases in atherosclerosis and abdominal aortic aneurysm (AAA) formation. We hypothesized that deficiency of AT1aR in adipocytes would reduce the development of obesity, obesity-induced disorders, and vascular diseases. To test this hypothesis, we created a …

Relation Of Total Homocysteine Level With Metabolic And Anthropometric Variables In Obese Children And Adolescents, Ayhan Abaci, Ahmet Zülfi̇kar Akelma, Osman Özdemi̇r, Şami̇l Hizli, Cem Hasan Razi, Kadi̇r Okhan Akin

Turkish Journal of Medical Sciences

To evaluate the total homocysteine (tHcy) level, a risk factor for atherosclerosis, atherothrombosis, and insulin resistance, for sex and pubertal state differences in obese children. Its relationship with metabolic and anthropometric parameters was also investigated. Materials and methods: The study involved obese children with a body mass index (BMI) above the 95th percentile who presented with the complaint of excessive weight gain, and healthy children with a BMI below the 85th percentile. Results: The study included 100 obese (mean age: 10.2 ± 2.7 years) and 71 healthy nonobese (mean age: 10.9 ± 2.6) children. A comparison of the data from …

Investigation Of The Results Of A Smoking Cessation Clinic And The Factors Associated With Success, Leyla Sağlam

Turkish Journal of Medical Sciences

To investigate the success rate and factors affecting success at a smoking cessation clinic. Materials and methods: In this study, 608 patients (397 male and 211 female) admitted to a smoking cessation clinic to quit smoking between 1 January 2006 and 1 June 2010 were investigated. Routine biochemical and hematological tests, pulmonary function tests, exhaled carbon monoxide levels, electrocardiographs, and chest X-rays were obtained from all of the patients. The questionnaire forms, including the Fagerström Test for Nicotine Dependence (FTND), were filled by all of the participants. At the end of months 6, 12, and 18, the smoking cessation success …

Regulation And Function Of Interleukin-21-Producing T Cells And Immune-Mediated Control Of Hiv-1 Infection, Latonya Denise Williams

All ETDs from UAB

CD8 T cells play a critical role in controlling intracellular pathogens, particularly viruses. However, during persistent viral infections, such as human immunodeficiency virus-1 (HIV-1) infection, virus-specific CD8 T cells become increasingly impaired by poorly understood mechanisms. Massive CD4 T cell depletion is a hallmark of HIV-1 infection and is associated with CD8 T cell dysfunction and ineffective viral containment. CD4 T cells provide critical helper signals to CD8 T cells, especially during uncontrolled viral infections. Mouse models of chronic viral infection implicate interleukin-21 (IL-21), produced primarily by CD4 T cells, as a vital factor necessary for the maintenance of fully …

Development Of Electrospun Bone-Mimetic Matrices For Bone Regenerative Applications, Matthew Christopher Phipps

All ETDs from UAB

Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein …

Evaluating The Efficacy Of Radiofrequency Amplitude-Modulated Electromagnetic Fields As A Novel Treatment For Hepatocellular Carcinoma, Jacquelyn Winifred Zimmerman

All ETDs from UAB

Hepatocellular carcinoma (HCC) incidence in the US is dramatically increasing. Five-year survival has remained 3-5% for the past several decades, demonstrating urgent need for additional therapies. Intrabuccal administration of amplitude-modulated radiofrequency electromagnetic fields (RF EMF) is a novel, minimally invasive treatment modality. Clinical evidence demonstrates this treatment approach elicits therapeutic responses in cancer patients. In vitro we have described a phenotype in HCC cells following RF EMF exposure that included proliferative inhibition, modulation of gene expression, and disruption of the mitotic spindle. This phenotype was specific for HCC cells exposed to HCC-specific RF EMF. We have demonstrated similar efficacy in …

Structural And Molecular Studies Of Nucleic Acid Chaperones, Lei Ding

All ETDs from UAB

Nucleic acids are the storage of genetic information that needs to be expressed and inherited. As abundant cellular macromolecules they are also major players of a wide variety of biological processes. They usually undergo post-transcriptional modifications and/or fold into higher order structures in order to accomplish their distinct functions. Most biological events involving nucleic acids are achieved by proteins that interact with them. The functionality requires specific recognition of nucleic acids by proteins at molecular level. Nucleic acid chaperones are a group of nucleic acids binding proteins that associate with structured RNAs or DNAs and assist correct folding of their …

Modulation Of Autoimmune Diabetes By B Cells Specific For N-Acetyl-D-Glucosamine, Brian L. Dizon

All ETDs from UAB

Type I diabetes (T1D) is an autoimmune disease in which ß cells are destroyed by the immune system; however, role of infections in type I diabetes (T1D) pathogenesis is unclear. Reports suggesting that childhood Group A Streptococcal (GAS) infections protected against T1D prompted us to study how antibodies to N-acetyl-D-glucosamine (GlcNAc), which are induced by GAS infection, influenced T1D development. We found that GlcNAc-specific antibodies reacted with ß cell secretory granules, and neonatal NOD mice immunized with GAS or given GAS-immune sera were protected from spontaneous diabetes. Monoclonal GlcNAc-specific IgM blocked activation and effector responses to islet antigens by diabetogenic …