Digital Commons Network^™

Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa

Department of Urology Faculty Papers

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived …

Sand Fly Fever: What Have We Learned In One Hundred Years?, David Brett-Major, David M. Claborn

Journal Articles: Epidemiology

Sand fly fever has severely impacted military missions in southern Europe and the Middle East for hundreds of years. After a brief respite following the malaria eradication programs of World War II, it has returned as a significant disease among residents in and travelers to the Mediterranean rim. It is a more severe disease now, with potential vectors in the United States. Sand fly fever is discussed in terms of its viruses, vectors, disease, control, and potential domestic impact.

Apd2: The Updated Antimicrobial Peptide Database And Its Application In Peptide Design., Guangshun Wang, Xia Li, Zhe Wang

Journal Articles: Pathology and Microbiology

The antimicrobial peptide database (APD, http://aps.unmc.edu/AP/main.php) has been updated and expanded. It now hosts 1228 entries with 65 anticancer, 76 antiviral (53 anti-HIV), 327 antifungal and 944 antibacterial peptides. The second version of our database (APD2) allows users to search peptide families (e.g. bacteriocins, cyclotides, or defensins), peptide sources (e.g. fish, frogs or chicken), post-translationally modified peptides (e.g. amidation, oxidation, lipidation, glycosylation or d-amino acids), and peptide binding targets (e.g. membranes, proteins, DNA/RNA, LPS or sugars). Statistical analyses reveal that the frequently used amino acid residues (>10%) are Ala and Gly in bacterial peptides, Cys and Gly in plant …

Snai1 And Snai2 Are Asymmetrically Expressed At The 2-Cell Stage And Become Segregated To The Te In The Mouse Blastocyst., Christine E Bell, Andrew J Watson

Obstetrics & Gynaecology Publications

SNAI1 and SNAI2 are transcription factors that initiate Epithelial-to-Mesenchymal cell transitions throughout development and in cancer metastasis. Here we show novel expression of SNAI1 and SNAI2 throughout mouse preimplantation development revealing asymmetrical localization of both SNAI1 and SNAI2 in individual blastomeres beginning at the 2-cell stage through to the 8-cell stage where SNAI1 and SNAI2 are then only detected in outer cells and not inner cells of the blastocyst. This study implicates SNAI1 and SNAI2 in the lineage segregation of the trophectoderm and inner cell mass, and provides new insight into these oncogenes.

Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M. Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela

Natural Sciences and Mathematics | Faculty Scholarship

In November-December 2007 a widespread seabird mortality event occurred in Monterey Bay, California, USA, coincident with a massive red tide caused by the dinoflagellate Akashiwo sanguinea. Affected birds had a slimy yellow-green material on their feathers, which were saturated with water, and they were severely hypothermic. We determined that foam containing surfactant-like proteins, derived from organic matter of the red tide, coated their feathers and neutralized natural water repellency and insulation. No evidence of exposure to petroleum or other oils or biotoxins were found. This is the first documented case of its kind, but previous similar events may have gone …

Genetic And Hormonal Factors Modulate Spreading Depression And Transient Hemiparesis In Mouse Models Of Familial Hemiplegic Migraine Type 1, Katharina Eikermann-Haerter, Ergin Dileköz, Chiho Kudo, Sean I Savitz, Christian Waeber, Michael J Baum, Michel D Ferrari, Arn M J M Van Den Maagdenberg, Michael A Moskowitz, Cenk Ayata

Faculty, Staff and Student Publications

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have …

Osteoarthritis Associated With Estrogen Deficiency., Jorge A Roman-Blas, Santos Castañeda, Raquel Largo, Gabriel Herrero-Beaumont

Jefferson Institute of Molecular Medicine Papers and Presentations

Osteoarthritis (OA) affects all articular tissues and finally leads to joint failure. Although articular tissues have long been considered unresponsive to estrogens or their deficiency, there is now increasing evidence that estrogens influence the activity of joint tissues through complex molecular pathways that act at multiple levels. Indeed, we are only just beginning to understand the effects of estrogen deficiency on articular tissues during OA development and progression, as well as on the association between OA and osteoporosis. Estrogen replacement therapy and current selective estrogen receptor modulators have mixed effectiveness in preserving and/or restoring joint tissue in OA. Thus, a …

Rhoa/Rho-Kinase Signaling: A Therapeutic Target In Pulmonary Hypertension, Scott A. Barman, Shu Zhu, Richard E. White

PCOM Scholarly Works

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling as well as inflammation. Rho-kinases (ROCKs) are one of the best-described effectors of the small G-protein RhoA, and ROCKs are involved in a variety of cellular functions including muscle cell contraction, proliferation and vascular inflammation through inhibition of myosin light chain phosphatase and activation of downstream mediators. A plethora of evidence in animal models suggests that heightened RhoA/ROCK signaling is important in the pathogenesis of pulmonary hypertension by causing enhanced constriction and remodeling of …

Mrn Complex Function In The Repair Of Chromosomal Rag-Mediated Dna Double-Strand Breaks, Beth A. Helmink, Andrea L. Bredemeyer, Baeck-Seung Lee, Ching-Yu Huang, Girdhar G. Sharma, Laura M. Walker, Jeffrey J. Bednarski, Wan-Ling Lee, Tej K. Pandita, Craig H. Bassing, Barry P. Sleckman

Open Access Publications

The Mre11-Rad50-Nbs1 (MRN) complex functions in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) at postreplicative stages of the cell cycle. During HR, the MRN complex functions directly in the repair of DNA DSBs and in the initiation of DSB responses through activation of the ataxia telangiectasia-mutated (ATM) serine-threonine kinase. Whether MRN functions in DNA damage responses before DNA replication in G0/G1 phase cells has been less clear. In developing G1-phase lymphocytes, DNA DSBs are generated by the Rag endonuclease and repaired during the assembly of antigen receptor genes by the process of V(D)J recombination. Mice and …

Comparative Efficacy Of Bioud To Other Commercially Available Arthropod Repellants Against The Ticks Amblyomma Americanum And Dermacentor Variabilis On Cotton Cloth, Brooke W. Bissinger, Jiwei Zhu, Charles S. Apperson, Daniel E. Sonenshine, D. Wesley Watson, R. Michael Roe

Biological Sciences Faculty Publications

BioUD is an arthropod repellent that contains the active ingredient 2-undecanone originally derived from wild tomato plants. Repellency of BioUD was compared with five commercially available arthropod repellents against the ticks Amblyomma americanum (L.) and Dermacentor variabilis Say in two-choice bioassays on treated versus untreated cotton cheesecloth. Overall mean percentage repellency against both species was greatest for and did not differ significantly between BioUD (7.75% 2-undecanone) and products containing 98.1% DEET, 19.6% IR3535, and 30% oil of lemon eucalyptus. Products containing 5% and 15% Picaridin and 0.5% permethrin were also repellent compared with untreated controls but to a lesser degree …

An Occupational Therapist's Manual For Animal Assisted Therapy With Emotionally Distrubed Adolescents, Ann Marie. Bilek, Hannah Osborne

Occupational Therapy Capstones

According to the comprehensive literature review, animals are currently being used as an effective tool during therapy and have been reported to promote improvement with communication, behaviors, quality of life, and self esteem of different treatment populations. Since emotionally disturbed adolescents often lack appropriate skills in the areas of communication, social interactions, self-esteem, independence, and boundaries, it can be challenging for occupational therapists to provide opportunities for development of these skills. Animal assisted therapy may be a tool that can assist in bridging the gap between the adult therapist and emotionally disturbed adolescents and provide a medium to promote skill …

A Reference Tool For Occupational Therapists To Utilize When Planning Occupation-Based Interventions Using Animal-Assisted Therapy, Jennifer L. Hamre, Kathryn E. Nagorka

Occupational Therapy Capstones

The purpose of this scholarly project was to develop a reference tool for occupational therapists to implement an animal-assisted therapy (AAT) program utilizing small animals in preparatory, purposeful, and occupation-based interventions. A thorough literature review was completed using PubMed, CINAHL, EBSCO, and OT Search to gain a comprehensive understanding of the current uses for small animals in a variety of settings. Cumulative resources included books, journal articles, editorials, magazines, and electronic organizational resources. Upon completion of a review of literature, we determined animals may be a beneficial modality and serve as an alternative mode of treatment to utilize with other …

Functional Interleukin-17 Receptor A Is Expressed In Central Nervous System Glia And Upregulated In Experimental Autoimmune Encephalomyelitis., Jayasri Das Sarma, Bogoljub Ciric, Ryan Marek, Sanjoy Sadhukhan, Michael L. Caruso, Jasmine Shafagh, Denise C. Fitzgerald, Kenneth S. Shindler, Am Rostami

Department of Neurology Faculty Papers

BACKGROUND: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.

METHODS: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ …

Combined Effects Of Hyperglycemic Conditions And Hiv-1 Nef: A Potential Model For Induced Hiv Neuropathogenesis., Edward A Acheampong, Cassandra Roschel, Muhammad Mukhtar, Alagarsamy Srinivasan, Mohammad Rafi, Roger J Pomerantz, Zahida Parveen

Department of Neurology Faculty Papers

Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using both in vitro and in vivo models. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for our in vitro study. The results show that in vitro hyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and …

Ca125/Muc16 Is Dispensable For Mouse Development And Reproduction, Dong-Joo Cheon, Ying Wang, Jian Min Deng, Zhen Lu, Lianchun Xiao, Chun-Ming Chen, Robert C Bast, Richard R Behringer

Faculty, Staff and Student Publications

Cancer antigen 125 (CA125) is a blood biomarker that is routinely used to monitor the progression of human epithelial ovarian cancer (EOC) and is encoded by MUC16, a member of the mucin gene family. The biological function of CA125/MUC16 and its potential role in EOC are poorly understood. Here we report the targeted disruption of the of the Muc16 gene in the mouse. To generate Muc16 knockout mice, 6.0 kb was deleted that included the majority of exon 3 and a portion of intron 3 and replaced with a lacZ reporter cassette. Loss of Muc16 protein expression suggests that Muc16 …

Mutation I810n In The Α3 Isoform Of Na+,K +-Atpase Causes Impairments In The Sodium Pump And Hyperexcitability In The Cns, Steven J. Clapcote, Steven Duffy, Gang Xie, Greer Kirshenbaum, Allison R. Bechard, Vivien Rodacker Schack, Janne Petersen, Laleh Sinai, Bechara J. Saab, Jason P. Lerch, Berge A. Minassian, Cameron A. Ackerley, John G. Sled, Miguel A. Cortez, Jeffrey T. Henderson, Bente Vilsen, John C. Roder

Psychology

In a mouse mutagenesis screen,weisolated a mutant, Myshkin (Myk), with autosomal dominant complex partial and secondarily generalized seizures, a greatly reduced threshold for hippocampal seizures in vitro, posttetanic hyperexcitability of the CA3-CA1 hippocampal pathway, and neuronal degeneration in the hippocampus. Positional cloning and functional analysis revealed that Myk/+ mice carry a mutation (I810N) which renders the normally expressed Na +,K+-. ATPase α3 isoform inactive. Total Na +,K+-ATPase activity was reduced by 42% in Myk/+ brain. The epilepsy in Myk/+ mice and in vitro hyperexcitability could be prevented by delivery of additional copies of wild-type Na+,K+-ATPase α3 by transgenesis, which also …

Behavioral Changes In Aging But Not Young Mice After Neonatal Exposure To The Polybrominated Flame Retardant Decabde, Deborah C. Rice, W. Douglas Thompson, Elizabeth A. Reeve, Kristen D. Onos, Mina Assadollahzadeh, Vincent P. Markowski

Psychology

BACKGROUND: After several decades of commercial use, the flame-retardant chemicals polybrominated diphenyl ethers (PBDEs) and their metabolites are pervasive environmental contaminants and are detected in the human body. Decabrominated diphenyl ether (decaBDE) is currently the only PBDE in production in the United States. oBjectives: Little is known about the health effects of decaBDE. In the present study we examined the effects of neonatal decaBDE exposure on behavior in mice at two ages. METHODS: Neonatal male and female C57BL6/J mice were exposed to a daily oral dose of 0, 6, or 20 mg/kg decaBDE from postnatal days 2 through 15. Two …

Noninvasive Measurement Of Aminolevulinic Acid-Induced Protoporphyrin Ix Fluorescence Allowing Detection Of Murine Glioma In Vivo, Summer L. Gibbs-Strauss, Julia A. O'Hara, P Jack Hoopes, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

Aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence is studied as a contrast agent for noninvasive detection of murine glioma, using the fluorescence-to-transmission ratio measured through the cranium. Signals measured prior to administration of ALA are very similar between control animals, 9L-GFP, and U251 tumor-bearing animals. However, 2 h after ALA administration, the PpIX signal from both tumor-bearing groups is significantly higher than the control group (9L-GFP group p-value=0.016, and U251 group p-value=0.004, relative to the control group). The variance in signal from the 9L-GFP group is much larger than either the control group or the U251 group, which is consistent …

Quantitative Imaging Of Scattering Changes Associated With Epithelial Proliferation, Necrosis And Fibrosis In Tumors Using Microsampling Reflectance Spectroscopy, Venkataramanan Krishnaswamy, P Jack Hoopes, Kimberley S. Samkoe, Julia A. O'Hara, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

Highly localized reflectance measurements can be used to directly quantify scatter changes in tissues. We present a microsampling approach that is used to raster scan tumors to extract parameters believed to be related to the tissue ultrastructure. A confocal reflectance imager was developed to examine scatter changes across pathologically distinct regions within tumor tissues. Tissue sections from two murine tumors, AsPC-1 pancreas tumor and the Mat-LyLu Dunning prostate tumor, were imaged. After imaging, histopathology-guided region-of-interest studies of the images allowed analysis of the variations in scattering resulting from differences in tissue ultra-structure. On average, the median scatter power of tumor …

Structure Altering Effects Of A Multicomponent Reading Intervention: An Application Of The Direct And Inferential Mediation (Dime) Model Of Reading Comprehension In Upper Elementary Grades, Georgios Kalantzis, Harel Z Shouval

Faculty, Staff and Student Publications

BACKGROUND: Synaptic plasticity underlies many aspect of learning memory and development. The properties of synaptic plasticity can change as a function of previous plasticity and previous activation of synapses, a phenomenon called metaplasticity. Synaptic plasticity not only changes the functional connectivity between neurons but in some cases produces a structural change in synaptic spines; a change thought to form a basis for this observed plasticity. Here we examine to what extent structural plasticity of spines can be a cause for metaplasticity. This study is motivated by the observation that structural changes in spines are likely to affect the calcium dynamics …

Molluscan Memory Of Injury: Evolutionary Insights Into Chronic Pain And Neurological Disorders, Edgar T Walters, Leonid L Moroz

Faculty, Staff and Student Publications

Molluscan preparations have yielded seminal discoveries in neuroscience, but the experimental advantages of this group have not, until now, been complemented by adequate molecular or genomic information for comparisons to genetically defined model organisms in other phyla. The recent sequencing of the transcriptome and genome of Aplysia californica, however, will enable extensive comparative studies at the molecular level. Among other benefits, this will bring the power of individually identifiable and manipulable neurons to bear upon questions of cellular function for evolutionarily conserved genes associated with clinically important neural dysfunction. Because of the slower rate of gene evolution in this molluscan …

Key Role Of T Cell Defects In Age-Related Vulnerability To West Nile Virus, James D. Brien, Jennifer L. Uhrlaub, Alec Hirsch, Clayton A. Wiley, Janko Nikolich-Zugich

Open Access Publications

West Nile virus (WNV) infection causes a life-threatening meningoencephalitis that becomes increasingly more prevalent over the age of 50 and is 40-50x more prevalent in people over the age of 70, compared with adults under the age of 40. In a mouse model of age-related vulnerability to WNV, we demonstrate that death correlates with increased viral titers in the brain and that this loss of virus control with age was the result of defects in the CD4 and CD8 T cell response against WNV. Specific age-related defects in T cell responses against dominant WNV epitopes were detected at the level …

Trem-2 (Triggering Receptor Expressed On Myeloid Cells 2) Is A Phagocytic Receptor For Bacteria, Elsa-Noah N'Diaye, Catherine S. Branda, Steven S. Branda, Lisette Nevarez, Marco Colonna, Clifford Lowell, Jessica A. Hamerman, William E. Seaman

Open Access Publications

Phagocytosis, which is essential for the immune response to pathogens, is initiated by specific interactions between pathogens and cell surface receptors expressed by phagocytes. This study identifies triggering receptor expressed on myeloid cells 2 (TREM-2) and its signaling counterpart DAP12 as a molecular complex that promotes phagocytosis of bacteria. Expression of TREM-2-DAP12 enables nonphagocytic Chinese hamster ovary cells to internalize bacteria. This function depends on actin cytoskeleton dynamics and the activity of the small guanosine triphosphatases Rac and Cdc42. Internalization also requires src kinase activity and tyrosine phosphorylation. In bone marrow-derived macrophages, phagocytosis is decreased in the absence of DAP12 …

Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima

Department of Biochemistry and Molecular Biology Faculty Papers

The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial …

Revealing Genes Associated With Vitellogenesis In The Liver Of The Zebrafish (Danio Rerio) By Transcriptome Profiling., Liraz Levi, Irena Pekarski, Ellen Gutman, Paolo Fortina, Terry Hyslop, Jakob Biran, Berta Levavi-Sivan, Esther Lubzens

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: In oviparous vertebrates, including fish, vitellogenesis consists of highly regulated pathways involving 17beta-estradiol (E2). Previous studies focused on a relatively small number of hepatic expressed genes during vitellogenesis. This study aims to identify hepatic genes involved in vitellogenesis and regulated by E2, by using zebrafish microarray gene expression profiling, and to provide information on functional distinctive genes expressed in the liver of a vitellogenic female, using zebrafish as a model fish. RESULTS: Genes associated with vitellogenesis were revealed by the following paired t-tests (SAM) comparisons: a) two-month old vitellogenic (Vit2) females were compared with non-vitellogenic (NV) females, showing 825 …

Developing Tta Transgenic Rats For Inducible And Reversible Gene Expression., Hongxia Zhou, Cao Huang, Min Yang, Carlisle P Landel, Pedro Yuxing Xia, Yong-Jian Liu, Xu Gang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

To develop transgenic lines for conditional expression of desired genes in rats, we generated several lines of the transgenic rats carrying the tetracycline-controlled transactivator (tTA) gene. Using a vigorous, ubiquitous promoter to drive the tTA transgene, we obtained widespread expression of tTA in various tissues. Expression of tTA was sufficient to strongly activate its reporter gene, but was below the toxicity threshold. We examined the dynamics of Doxycycline (Dox)-regulated gene expression in transgenic rats. In the two transmittable lines, tTA-mediated activation of the reporter gene was fully subject to regulation by Dox. Dox dose-dependently suppressed tTA-activated gene expression. The washout …

Micrornas: Key Modulators Of Posttranscriptional Gene Expression., Steven P. O'Hara, Justin L. Mott, Patrick L. Splinter, Gregory J. Gores, Nicholas F. Larusso

Journal Articles: Biochemistry & Molecular Biology

No abstract provided.

Mitochondrial Fragmentation Is Involved In Methamphetamine-Induced Cell Death In Rat Hippocampal Neural Progenitor Cells., Changhai Tian, L. Charles Murrin, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

Methamphetamine (METH) induces neurodegeneration through damage and apoptosis of dopaminergic nerve terminals and striatal cells, presumably via cross-talk between the endoplasmic reticulum and mitochondria-dependent death cascades. However, the effects of METH on neural progenitor cells (NPC), an important reservoir for replacing neurons and glia during development and injury, remain elusive. Using a rat hippocampal NPC (rhNPC) culture, we characterized the METH-induced mitochondrial fragmentation, apoptosis, and its related signaling mechanism through immunocytochemistry, flow cytometry, and Western blotting. We observed that METH induced rhNPC mitochondrial fragmentation, apoptosis, and inhibited cell proliferation. The mitochondrial fission protein dynamin-related protein 1 (Drp1) and reactive oxygen …

Effector Memory T Cell Responses Are Associated With Protection Of Rhesus Monkeys From Mucosal Simian Immunodeficiency Virus Challenge., Scott G. Hansen, Cassandra Vieville, Nathan Whizin, Lia Coyne-Johnson, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Michael K. Axthelm, Kelli Oswald, Charles M. Trubey, Michael Piatak, Jeffrey D. Lifson, Jay A. Nelson, Michael A. Jarvis, Louis J. Picker

School of Biomedical Sciences

The rapid onset of massive, systemic viral replication during primary HIV or simian immunodeficiency virus (SIV) infection and the immune evasion capabilities of these viruses pose fundamental problems for vaccines that depend upon initial viral replication to stimulate effector T cell expansion and differentiation. We hypothesized that vaccines designed to maintain differentiated effector memory T cell (TEM cell) responses at viral entry sites might improve efficacy by impairing viral replication at its earliest stage, and we have therefore developed SIV protein-encoding vectors based on rhesus cytomegalovirus (RhCMV), the prototypical inducer of life-long TEM cell responses. RhCMV vectors expressing SIV Gag, …

The Eagleville Times,Volume 6, Issue 24, Debbie Ryan

Eagleville Times

No abstract provided.