Immunology and Infectious Disease Commons^™

Construction Of A Live-Attenuated Hiv-1 Vaccine Through Genetic Code Expansion, Nanxi Wang, Yue Li, Wei Niu, Ming Sun, Ronald Cerny, Qingsheng Li, Jiantao Guo

Qingsheng Li Publications

A safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) is urgently needed to combat the worldwide AIDS pandemic, but still remains elusive. The fact that uncontrolled replication of an attenuated vaccine can lead to regaining of its virulence creates safety concerns precluding many vaccines from clinical application. We introduce a novel approach to control HIV-1 replication, which entails the manipulation of essential HIV-1 protein biosynthesis through unnatural amino acid (UAA*)-mediated suppression of genome-encoded blank codon. We successfully demonstrate that HIV-1 replication can be precisely turned on and off in vitro.

Includes supporting information.

Light Stimulates The Mouse Adrenal Through A Retinohypothalamic Pathway Independent Of An Effect On The Clock In The Suprachiasmatic Nucleus, Silke Kiessling, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The brain’s master circadian pacemaker resides within the hypothalamic suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night cycle via the retinohypothalamic tract and the SCN provides temporal information to the central nervous system and to peripheral organs that function as secondary oscillators. The SCN clock-cell network is thought to be the hypothalamic link between the retina and descending autonomic circuits to peripheral organs such as the adrenal gland, thereby entraining those organs to the day/night cycle. However, there are at least three different routes or mechanisms by which retinal signals transmitted to the hypothalamus may be conveyed …

Dens Agenesis And Cervical Vertebral Malformation In A Labrador Retriever Puppy, Elisa Salas, Henry E. Cerny, Seth P. Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

Cervical vertebral malformations can cause acute or progressive pain, paralysis, and potentially death. Herein we present a case report of dens agenesis; cervical vertebral malformations of C1, C2, C6, and C7; subluxation of C1 and C2 and C4 and C5; and associated degenerative myelopathy in a 5-month-old female Labrador Retriever puppy. We additionally review current knowledge regarding pathogenesis and treatment.

Role Of Scavenger Receptor Class B Type I In Thymopoiesis, Zhong Zheng

Theses and Dissertations--Nutritional Sciences

T cells, which constitute an essential arm in the adaptive immunity, complete their development in the thymus through a process called thymopoiesis. However, thymic involution can be induced by a couple of factors, which impairs T cell functions and is slow to recover. Therefore, understanding how thymopoiesis is regulated may lead effort to accelerate thymic recovery and improve immune functions in thymocyte-depleted patients. In this project, we identified scavenger receptor BI (SR-BI), a high density lipoprotein (HDL) receptor, as a novel modulator in thymopoiesis. In mice, absence of SR-BI causes a significant reduction in thymus size after puberty and a …

The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence

Theses and Dissertations

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells. The affected cytokines …

Glut 4 And Insulin Resistance, Salmin Ali

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Five types of glucose transporters stimulate the transport of glucose from the bloodstream into cells such as muscle cells and adipocytes in response to insulin signaling or exercise. Skeletal muscle and adipose tissue are the main sites for glucose uptake and dispose in insulin action dependent pathway. In non-insulin stimulated condition, the GLUT4 storage vesicles stay away from the plasma membrane, so there is no GLUT4 translocation or GLUT4 mediated glucose uptake. However, in insulin stimulated state, insulin initiates insulin signaling cascade which results in rapid GLUT4 translocation and increased glucose uptake at the cell surface. Failure of the translocation …

The Impact Of Down Syndrome And Folate Depletion On Genomic Stabilizing Pathways Of Lymphoblastoid Cells, Khadijah Ibrahim Alnabbat

Wayne State University Theses

Understanding the role of nutrition plays in Down syndrome (DS) could help in the development and implementation of strategies that help overcome the negative consequences phenotypes of Down syndrome. Conserving genome integrity is crucial for cells to survive, and thus understanding how genetic defects induce damage to genomic DNA and impair subsequent repair of this damage is important. Evidence accumulated points to increased DNA damage and mutation accumulation associated with a decline in DNA repair capacity, Base Excision Repair (BER) in particular. Thus, the successful clinical management of DS resides in understanding the metabolic imbalance provoked by overexpression of genes …

Regulation Of Immune Response Genes By Vitamin D In Mammary Epithelial Cells With An Emphasis On Cd14, Katrina Marie Simmons

Legacy Theses & Dissertations (2009 - 2024)

Vitamin D is primarily known for its role in bone health, however recently vitamin D has been identified as a potent immunomodulator. Most research studying the effects of vitamin D on immune properties have focused on immune cells. Few have evaluated how vitamin D affects the immune functions of barrier epithelial cells, such as human mammary epithelial (HME) cells, that are exposed to pathogens both locally and systemically. The goals of the studies described in this thesis were to comprehensively and mechanistically evaluate the immune effects of vitamin D metabolites, 1α,25-dihydroxyvitamin D (1,25D) and 25-hydroxyvitamin D (25D), on HME cells. …

Resurrection And Redescription Of Varestrongylus Alces (Nematoda: Protostrongylidae), A Lungworm Of The Eurasian Moose (Alces Alces), With Report On Associated Pathology, Guilherme G. Verocai, Eric P. Hoberg, Turid Vikøren, Kjell Handeland, Bjørnar Ytrehus, Andrew M. Rezansoff, Rebecca K. Davidson, John S. Gilleard, Susan J. Kutz

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Background: Varestrongylus alces, a lungworm in Eurasian moose from Europe has been considered a junior synonym of Varestrongylus capreoli, in European roe deer, due to a poorly detailed morphological description and the absence of a type-series.

Methods: Specimens used in the redescription were collected from lesions in the lungs of Eurasian moose, from Vestby, Norway. Specimens were described based on comparative morphology and integrated approaches. Molecular identification was based on PCR, cloning and sequencing of the ITS-2 region of the nuclear ribosomal DNA. Phylogenetic analysis compared V. alces ITS-2 sequences to these of other Varestrongylus species …

Novel Gammaherpesvirus Functions 1 Encoded By Bovine Herpesvirus (Bovine Lymphotropic Virus), J. Jia, G. Delhon, E. R. Tulman, D. G. Diel, Fernando A. Osorio, X. Wen, G. F. Kutish, D. L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

The genus Macavirus of the subfamily Gammaherpesvirinae includes viruses that infect lymphoid cells of domestic and wild ruminants and swine, causing asymptomatic latent infections in reservoir hosts. Here, we describe the genome of bovine herpesvirus 6 (BoHV-6), a

macavirus ubiquitous in healthy cattle populations. The BoHV-6 genome exhibited architecture conserved in macaviruses, including a repetitive H-DNA region and unique, 141 kilobase pair L

DNA region predicted to encode 77 genes. BoHV-6 encoded in variable genomic regions a novel complement of genes relative to other characterized macaviruses, likely contributing to distinctive aspects of BoHV-6 infection biology and host range. Most notably, …

Role Of The Intestinal Microbiota In Gut Barrier Dysfunction Following Burn Injury, Zachary Earley

Master's Theses

Burn injury represents a major medical problem with half a million cases requiring medical attention and 4,000 deaths reported annually. Sepsis and multiple organ failure remain the leading causes of death following injury, and may be brought on by bacterial infections or toxins. The gastrointestinal tract contains approx. 100 trillion microbes; therefore, the indigenous commensal microbiota may play a role in leading to these complications or infections in burn patients. The overall objective of this project is to identify a potential mechanism whereby changes in gut bacteria may lead to intestinal inflammation or bacterial translocation--key factors which may lead to …

Differentiation Of U-937 Monocytes To Macrophage-Like Cells Polarized Into M1 Or M2 Phenotypes According To Their Specific Environment: A Study Of Morphology, Cell Viability, And Cd Markers Of An In Vitro Model Of Human Macrophages, Fatma Husien S. Abdulhadi

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In this study, the human leukemic monocyte lymphoma cell line U-937 was used as an in vitro model for monitoring monocyte/macrophage differentiation. Phorbol 12- myristate (13) (PMA) was used to activate U-937 cells into macrophage-like cells (M0). After 24 hours of PMA treatment, non- adherent U-937 cells became tightly adherent to the culture plates forming M0 cells. M0 cells were then polarized into the M1 macrophage phenotype by treatment with LPS and IFN-γ for another 24 hours. Each of the cytokines IL-4, IL-13, or IL-10 was applied separately to three M0 cultures for 24 hours to induce the M2 macrophage …

Modulation Of Vaccine-Induced Responses By Anthelmintic Treatment In Ponies, Emily Rubinson

Theses and Dissertations--Medical Sciences

Vaccines and anthelmintics induce an inflammatory response in equids. Since they are commonly given concurrently, it is practical to study any interaction between them. This study evaluated whether IVM and PYR would modulate the acute phase inflammatory response, the systemic gene expression of pro-inflammatory cytokines, and vaccine-specific titers induced by WNV, EHV, and KLH vaccines. Naturally-infected, yearling ponies were sorted by gender, then fecal epgs. They were randomly assigned to three treatment groups: IVM, PYR, and control. All ponies received vaccinations intramuscularly on days 0 and 29. Whole blood, serum, and plasma samples were collected 1, 3, and 14 days …

Role Of Viral And Host Factors In Influenza Virus Mediated Inhibition Of Interleukin-23, Ashish Tiwari

Theses and Dissertations--Veterinary Science

Influenza virus is one of the major respiratory pathogens of humans as well as animals, including equines. There is an increasing evidence that bacterial infections are the most common cause of the death during influenza. In horses also, secondary bacterial pneumonia can lead to death, and surviving horses may take up to six months for the complete recovery resulting in heavy economic loss to the equine industry. Interleukin (IL)-23 mediated innate immune response has been shown to protect the host from various respiratory bacterial infections. However, studies to investigate the role of host and viral factors in the regulation of …

The Modulation Of Mucosal Immune Markers, Urs, And Psychological Parameters Following Acute And Chronic Exercise, Carole Ann Sloan

Wayne State University Dissertations

The purpose of this dissertation was to evaluate changes in two antimicrobial markers, upper respiratory symptom (URS) variables, and mood state following participation in an acute (N = 93) and chronic (N = 88) observational study of college aerobic exercise, yoga exercise, and non-exercise classes.

METHODS: Unstimulated whole saliva was collected pre/post-acute (50 minutes) and pre/midpoint/post-chronic (12 weeks) during the study period. Saliva was analyzed for salivary immunoglobulin A (SIgA) and salivary alpha amylase (SAA) using protocols and assay kits by Salimetrics, upper respiratory symptoms (URS) were evaluated using the Wisconsin Upper Respiratory Symptom Survey (WURSS), and mood states were …

Socs1/Socs3 Expression And Virus Replication Of Denv2 And Hsv-1 In Cytokine-Polarized Subsets Of Raw 264.7 Macrophages, Nagarjuna Reddy Cheemarla

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Cytokine activation of macrophages leads to "macrophage polarizatio" The M1 subset is polarized by exposure to lipopolysaccharide (LPS) and interferon-gamma (IFN-γ) and M2 polarized cells develop after exposure to interleukin-4 (IL-4) or IL-13. In this study, the RAW 264.7 murine macrophage cell line was used to study the effect herpes simplex virus-Type I (HSV-1) and Dengue virus serotype-2 (DENV2) infections have on cultures of unpolarized (M0) or polarized subsets. The macrophage subsets were characterized using cluster of differentiation markers CD14 and CD86. Uninfected M1 macrophages showed up regulation in expression of the co-stimulatory factor B7.2 (CD86) compared to expression by …

Development Of A Co-Culture System To Mimic The Transfection Of Hsv-1 From Keratinocytes To Neuronal Cells, David A. Dixon

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To more closely mimic the in vivo progression of HSV-1 a novel in vitro method was created. In this study HEL-30 keratinocytes were infected with a 0.1 MOI of HSV-1 and plated unto a membrane with 8μm diameter pores. The membrane insert was then placed into culture wells that contained Neuro-2a cells (N2A). The neurites from the neuronal cells made cell-to-cell contact with the infected HEL-30 cells and the virus was transmitted into the neuronal cells. To determine if infection occurred in the N2A cells the cells were lysed and the lysate incubated with Vero cells to titrate virus plaque …

White Blood Cell Counts, Parasite Prevalence, And Plasma Cortisol Levels Of Dogs In A County Animal Shelter: Changes Over Days And Impact Of A Program Of Repeated Human Interaction, Emily S. Dudley

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Animal shelter housing is highly stressful for a dog, compromising welfare and leading to undesirable behaviors and unknown health consequences. We documented the changes in circulating numbers of white blood cells, plasma cortisol, and fecal parasite shedding of dogs housed for 10 days at a county animal shelter. White blood cell changes were most prominent on Day 10 after arrival to the shelter. Changes included increased total leukocytes, mature neutrophils, and lymphocytes, with less consistent increases in monocytes and neutrophil to lymphocyte ratio (N:L). Fecal parasite shedding was elevated and not affected by day. Cortisol levels of shelter dogs declined …

Identification Of The Sites Of Action Of Inhibitors Of Mammalian Phospholipase D2 (Pld2) And The Role Of Interacting Protein Partners, Ramya Ganesan

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Phospholipase D (PLD) is a key enzyme for the remodeling of phospholipids in the cell membrane. PLD has been implicated in many physiological functions such as chemotaxis and phagocytosis as well as pathological functions such as ischemia/reperfusion and cancer metastasis. Several small molecule inhibitors of PLD have been recently developed to overcome these pathological effects. We have concentrated on 5-Fluoro-2-Indolyl des-Chlorohalopemide (FIPI) which is an indole derivative of halopemide that inhibits the two mammalian isoforms PLD1 and PLD2. We also concentrate on N-[2-[1-(3-Fluorophenyl)-4-oxo-1,3,-8-triazaspiro[4.5]dec-8-yl]ethyl]-2-naphthalenecarboxamide (NFOT) and N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)ethyl]-2-naphthalenecarboxamide (NOPT) that are specific inhibitors of the PLD2 isoform. In spite of knowing their …

Comparison Between Flow Cytometry And Bead Method In Counting Cd4 And Cd8 T Lymphocytes In Mouse Spleen Cells Suspension, Abdulrahman Abdalla Allabidi

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The flow cytometry is gold standard method to count CD4, CD8 human T lymphocytes, and calculate CD8 to CD4 ratio in HIV patients peripheral blood to stage them and monitor their response to treatment. In this study, a comparison was made by counting CD4and CD8 mouse spleen T lymphocytes by flow cytometry, and a method involving antibody coated latex beads. The bead method yielded results comparable to those obtained by flow cytometry. These results indicate that antibody coated beads are suitable to determine CD4 and CD8 + T lymphocytes counts in situation where flow cytometry is not readily available.