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Mechanisms And Countermeasures Of Microgravity Induced Bone Loss: In Vitro And In Vivo Model Systems, Ritu Saxena Jan 2009

Mechanisms And Countermeasures Of Microgravity Induced Bone Loss: In Vitro And In Vivo Model Systems, Ritu Saxena

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Rapid bone loss occurs during prolonged periods of weightlessness experienced by astronauts during spaceflights which leads to osteopenia and increased fracture risk upon return to earth. Spaceflight studies have shown that the bone loss occurs as a result of both a decrease in bone formation and an increase in bone resorption, however, the molecular mechanisms still need to be elucidated. Previous studies from our laboratory and other groups have indicated that modeled microgravity leads to inhibition of osteoblastogenesis and a stimulation of adipogenesis of human mesenchymal stem cells in osteogenic medium which is most likely mediated by a decrease in …

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Non-Shared Familial Environment As A Determinant Of Discordant Patterns Of Disordered Eating Behaviors Among Sibling Pairs In A Family, Suparna Bagchi Jan 2009

Non-Shared Familial Environment As A Determinant Of Discordant Patterns Of Disordered Eating Behaviors Among Sibling Pairs In A Family, Suparna Bagchi

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Worldwide 15-40% of adolescents practice Disordered Eating Behavior (DEB). This study examined DEB development and the role of 1) shared familial factors among sibling pairs; and 2) non-shared familial experiences among discordant sibling pairs adjusted for individual and shared familial factors. The "National Longitudinal Study of Adolescent Health" data on 3274 adolescents were analyzed. The sample contained: twins (n=952), full siblings (n=1434), half siblings (n=418), and biologically not-related siblings (n=470). Multivariable regression analysis examined familial factors associated with DEB in the overall sample and sibling pair types. Adolescents engaging in DEB (~16%) were more likely to be white females with …

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Immunotherapy Of Cancer Employing Γδ-T Cells: A Study Examining Their Utility And Feasibility, Benjamin Hester Beck Jan 2009

Immunotherapy Of Cancer Employing Γδ-T Cells: A Study Examining Their Utility And Feasibility, Benjamin Hester Beck

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Unlike antigen-specific alpha beta-T cells, gamma delta-T cells can recognize and lyse cancerous cells rapidly upon encounter in a manner that does not require the recognition of tumor-specific antigens. Given the well-documented capacity of gamma delta-T cells to innately kill malignant cells, efforts are now underway to exploit the antitumor properties of gamma delta-T cells for clinical purposes. Here, we present for the first time preclinical in vivo mouse models of gamma delta-T cell-based immunotherapy directed against breast cancer. These studies were explicitly designed to approximate clinical situations in which adoptively-transferred gamma delta-T cells would be employed therapeutically against breast …

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Identification Of New Strategies For The Treatment Of Glioblastoma Multiforme Utilizing A Pharmacogenomic Approach: Genetic Profiles Associated With Patient Prognosis And Outcome To Capecitabine Treatment, Jessica Marie Grunda Jan 2009

Identification Of New Strategies For The Treatment Of Glioblastoma Multiforme Utilizing A Pharmacogenomic Approach: Genetic Profiles Associated With Patient Prognosis And Outcome To Capecitabine Treatment, Jessica Marie Grunda

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Glioblastoma multiforme (GBM) is the most lethal form of primary brain neoplasm with average patient survival between 9 and 15 months even with the most aggressive treatment modalities. Unfortunately, this poor outcome has not appreciably changed in the past 50 years emphasizing the lack of traditional `trial and error' methods in identifying an efficacious treatment for GBM. Pharmacogenomics is greatly impacting cancer research through the development of personalized medicine and rationally designed treatment paradigms for the development of more efficacious and less toxic treatment modalities. The main objective of this research was to utilize a pharmacogenomic approach to identify new …

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Identification Of The Function Of Rv0194 In Mycobacterium Tuberculosis, Rachel Philpott Jan 2009

Identification Of The Function Of Rv0194 In Mycobacterium Tuberculosis, Rachel Philpott

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No abstract provided.

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The Role Of The Ss2-Integrin Family On T Cell Subsets, Jillian E. Wohler Jan 2009

The Role Of The Ss2-Integrin Family On T Cell Subsets, Jillian E. Wohler

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Members of the ß2-integrin family of adhesion molecules, CD11a, CD11b, and CD11c, have all been shown to play a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). CD11d had yet to be studied in demyelinating disease and its functions remained unclear. We report here that CD11d is the only member of the ß2-integrin family of adhesion molecules that fails to protect against the development of EAE. Surprisingly, the EAE studies suggested that CD11a, CD11b, and CD11c were all contributing to T cell activity during disease development by mechanisms beyond the migration of these cells into the CNS. However, the …

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Monosodium L-Glutamate Exposure Adversely Affects Early Development In The Sea Urchin Lytechinus Variegatus, Dorothy B. Moseley Jan 2009

Monosodium L-Glutamate Exposure Adversely Affects Early Development In The Sea Urchin Lytechinus Variegatus, Dorothy B. Moseley

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No abstract provided.

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Mechanism Of Centaurin Alpha -1 Control Of Neuronal Differentiation, Donna Monique Hill Jan 2009

Mechanism Of Centaurin Alpha -1 Control Of Neuronal Differentiation, Donna Monique Hill

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No abstract provided.

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“I Talk To God But The Sky Is Empty:” W.B. Yeats’S Influence On Sylvia Plath’S Renunciation Of Christianity, Rachel Leigh Anderson Jan 2009

“I Talk To God But The Sky Is Empty:” W.B. Yeats’S Influence On Sylvia Plath’S Renunciation Of Christianity, Rachel Leigh Anderson

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No abstract provided.

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Bone Properties Surrounding Ha-Coated Custom Osseous Integrated Dental Implants, Maribel Ibañez Baker Jan 2009

Bone Properties Surrounding Ha-Coated Custom Osseous Integrated Dental Implants, Maribel Ibañez Baker

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No abstract provided.

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A Comparison Of Two Soft Tissue Gingivectomy Techniques, James R. Durham Jan 2009

A Comparison Of Two Soft Tissue Gingivectomy Techniques, James R. Durham

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No abstract provided.

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A Detailed Look At The Familial, Social, And Clinical Contexts For Children After The Identification Of Maltreatment, Lindsay M. Duty Jan 2009

A Detailed Look At The Familial, Social, And Clinical Contexts For Children After The Identification Of Maltreatment, Lindsay M. Duty

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No abstract provided.

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A Comparison Of Allogenous Bone Graft Versus Particulate Autogenous Bone Graft To Gain Increase In Vertical And Horizontal Dimension Prior To Implant Placement. A Human Clinical Study., Elfa Gudmundsdottir Jan 2009

A Comparison Of Allogenous Bone Graft Versus Particulate Autogenous Bone Graft To Gain Increase In Vertical And Horizontal Dimension Prior To Implant Placement. A Human Clinical Study., Elfa Gudmundsdottir

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No abstract provided.

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Development And Application Of A Technique To Measure Soft Tissue Changes Following Noncarious Cervical Lesion Restorations, Prabhavathi Jampani Jan 2009

Development And Application Of A Technique To Measure Soft Tissue Changes Following Noncarious Cervical Lesion Restorations, Prabhavathi Jampani

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No abstract provided.

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Effects Of Cyclic Strain On Tgf-Ss1 Activation And Phenotype Modulation The Aortic Valve Interstitial Cells, Michael P. Nilo Jan 2009

Effects Of Cyclic Strain On Tgf-Ss1 Activation And Phenotype Modulation The Aortic Valve Interstitial Cells, Michael P. Nilo

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No abstract provided.

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Development And Implementation Of Knock-In And Bac-In Il-2 Reporter Mouse Models To Characterize Il2 Gene Regulation In Cd4 T Cells, Rita Jeanne Luther Jan 2009

Development And Implementation Of Knock-In And Bac-In Il-2 Reporter Mouse Models To Characterize Il2 Gene Regulation In Cd4 T Cells, Rita Jeanne Luther

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Maintenance of immune homeostasis involves a balance between T cell effector responses to antigen stimulus and reciprocal downregulation of this response through peripheral tolerance mechanisms. Upon exposure to pathogen, cytokine production and signaling serve to tightly coordinate cell-mediated clearance of antigen followed by contraction of the immune response. Interkeukin-2 (IL-2) is a type I family cytokine critical for expansion of activated T cells in vitro and enhancement of T cell memory responses in vivo. Deficiency of IL-2 in vivo also revealed a critical role for IL-2 in immune tolerance through the maintenance of T regulatory cell populations (Treg) in peripheral …

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The Significance Of Heavy Chain Cdr3 Diversity In The Antibody Response To Polysaccharides, Tamer Mahmoud Jan 2009

The Significance Of Heavy Chain Cdr3 Diversity In The Antibody Response To Polysaccharides, Tamer Mahmoud

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An understanding of the molecular mechanisms involved in the generation of protective antibody responses to polysaccharides associated with pathogenic microorganisms is of importance for improving vaccine design. The heavy chain third complementarity-determining region (HCDR3) of an antibody molecule is at the center of its antigen-binding site and plays a determinative role in antigen recognition. The goal of this dissertation was to investigate the role of HCDR3 diversity and composition on the antibody response to the polysaccharide α 1→3 Dextran (DEX). In the first study, we investigated the role of TdT, a DNA polymerase that plays a major role in generating …

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The Acute Onset Of Insulin Resistance In Adipose Tissue Following Trauma And Hemorrhage, Vanessa L. Williams Jan 2009

The Acute Onset Of Insulin Resistance In Adipose Tissue Following Trauma And Hemorrhage, Vanessa L. Williams

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Insulin resistance and hyperglycemia are common findings in patients following acute illnesses or injuries, such as surgical trauma, thermal injury, infection, hemorrhage, and sepsis. Insulin has three main target tissues: liver, skeletal muscle, and adipose tissue. Insulin resistance in the liver results in an increase in gluconeogenesis. In skeletal muscle, insulin resistance causes a decrease in insulin-stimulated glucose uptake. However, little is known about the contribution that adipose tissue makes to the insulin resistant state. The goals of the research presented in this dissertation were to: 1) determine whether insulin resistance developed in adipose tissue following acute trauma and hemorrhage; …

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Analysis Of Cystic Kidney Disease-Related Genes In Caenorhabditis Elegans, Corey L. Williams Jan 2009

Analysis Of Cystic Kidney Disease-Related Genes In Caenorhabditis Elegans, Corey L. Williams

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Cilia are evolutionarily conserved, membrane-bound, microtubule-based organelles found on a diverse array of cell types in eukaryotic organisms. Inherited diseases of cilia protein dysfunction include Nephronophthisis (NPHP), Joubert Syndrome (JBTS), Meckel-Gruber Syndrome (MKS), and Bardet-Biedl Syndrome (BBS). Important insight in the basic cell biological functions of BBS and NPHP proteins has been gained from analysis in the nematode Caenorhabditis elegans. My goal in this dissertation was to model MKS protein function in cilia biology utilizing the powerful genetic malleability of C. elegans. mks-1 and mks-3, the C. elegans homologs of two MKS-associated proteins in humans, were selected for this analysis. …

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Modification Of Adenovirus Capsid Proteins For Gene Therapy Applications, Yizhe Tang Jan 2009

Modification Of Adenovirus Capsid Proteins For Gene Therapy Applications, Yizhe Tang

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Adenovirus (Ad) is the most commonly used viral vector in gene therapy applications to date for a broad range of diseases. Although Ad-based viral vectors have many advantages in a variety of gene therapy designs, the commonly used adenoviral vectors have several key shortcomings. Those shortcomings include (1) inefficient transduction in cell types devoid of Ad’s native receptors and the incapability of gene delivery to targets behind physical barriers; (2) restricted accessibility to the central nerve system due to the existence of the blood-brain barrier (BBB); (3) lack of a useful strategy and platform to generate multi-functionality displaying Ad vectors …

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Axonal Trafficking Of Bmp Signals In Drosophilia Motoneurons, Rebecca Burt Smith Jan 2009

Axonal Trafficking Of Bmp Signals In Drosophilia Motoneurons, Rebecca Burt Smith

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The Drosophila Bone Morphogenetic Protein (BMP) Glass bottom boat (Gbb) is a ligand for the BMP type II receptor, Wishful thinking (Wit). Mutations in either of these proteins impair synaptic growth at the neuromuscular junction (NMJ). Gbb is a retrograde signal (from target to innervating neuron) that is essential for proper NMJ development and function. Tissue-specific rescue of pathway mutants and immunolocalization experiments indicate that the receptor-ligand interaction occurs at the NMJ, and results in the nuclear accumulation of the phosphorylated form of the transcription factor Mad, indicating that retrograde transport along the axon is critical for pathway activation. We …

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The Essential Role Of Macrophages And Tlr Signaling In The Host Response To Mycoplasma Pneumoniae, Jen-Feng Lai Jan 2009

The Essential Role Of Macrophages And Tlr Signaling In The Host Response To Mycoplasma Pneumoniae, Jen-Feng Lai

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Several reports have suggested that Mycoplasma pneumoniae (Mp) can contribute importantly to the expression of symptoms in asthmatic human subjects. As a foundation for understanding the interactions between Mp and asthma susceptibility, we first studied the mechanisms by which the host normally eliminated Mp. Mice were inoculated with 4x106 Mp intranasally. Twenty-four hours after inoculation with Mp, subpopulations of CD11b+ macrophages/monocytes had been recruited into the lungs. The clearance of Mp was impaired both in macrophage-depleted and in macrophage-deficient mice. Furthermore, mice deficient in MyD88, a major adaptor for TLR signaling, showed dramatically defective clearance of Mp, associated with reduced …

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Structural Studies Of Yeast Mitochondrial Peripheral Membrane Protein Tim44, Ratnakar Josyula Jan 2009

Structural Studies Of Yeast Mitochondrial Peripheral Membrane Protein Tim44, Ratnakar Josyula

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Tim44 is a peripheral membrane protein and a component of the TIM23 translocon on the matrix side. It is well established that Tim44 tethers the presequence associated motor (PAM) complex to the Inner Mitochondrial Membrane (IMM), through its C-Terminal Domain (CTD). This study focuses on understanding the high resolution structure of Tim44 CTD and the molecular basis for its membrane anchoring mechanism. The crystal structure of Tim44 CTD revealed that it exists as a single domain. The N-terminal amphipathic helices A1 and A2 protrude away from the main body of Tim44 CTD. These two flexible helices have been tested for …

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Multi-Component Nanofibrous Scaffolds With Tunable Properties For Bone Tissue Engineering, Moncy V. Jose Jan 2009

Multi-Component Nanofibrous Scaffolds With Tunable Properties For Bone Tissue Engineering, Moncy V. Jose

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Bone is a highly complex tissue which is an integral part of vertebrates and hence any damage has a major negative effect on the quality of life. Tissue engineering is regarded as an ideal route to resolve the issues related to the scarcity of tissue and organ for transplantation. Apart from cell line and growth factors, the choice of materials and fabrication technique for scaffold are equally important. The goal of this work was to develop a multi-component nanofibrous scaffold based on a synthetic polymer (poly(lactic-co-glycolide) (PLGA)), a biopolymer (collagen) and a biomineral (nano-hydroxyapatite (na-no-HA)) by electrospinning technique, which mimics …

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Mouse Model Of Cooley's Anemia, Yongliang Huo Jan 2009

Mouse Model Of Cooley's Anemia, Yongliang Huo

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β thalassemia major or Cooley’s anemia (CA) is a heterogeneous group of inherited disorders characterized by deficient β globin chain production. Newborns with CA are healthy because of the high fetal hemoglobin (HbF) levels present in their red blood cells (RBCs). As HbF levels decline during the first year of life, patients develop severe anemia that necessitates regular blood transfusion to maintain life. CA has been difficult to model in the mouse due to the lack of a fetal hemoglobin equivalent in the mouse. By utilizing a human fetal to adult delayed hemoglobin switching cassette, I hypothesize that a CA …

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Polycistronic Lentiviral Vector For Hit And Run Reprogramming Of Mouse And Human Somatic Cells To Induced Pluripotent Stem Cell, Chia-Wei Chang Jan 2009

Polycistronic Lentiviral Vector For Hit And Run Reprogramming Of Mouse And Human Somatic Cells To Induced Pluripotent Stem Cell, Chia-Wei Chang

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Embryonic stem (ES) cells are pluripotent and, therefore, can differentiate into most if not all somatic cell types. Because of this characteristic, ES cells have great potential for medical therapies. Since the first cloned mammal, Dolly the sheep, was published in 1996 (1), several groups have successfully cloned other animals by the same nuclear transfer method (2). Isogenic ES cell lines can also be established from donor cells by the same technique (3). However, to date there has been no report of successful derivation of human ES cells by nuclear transfer. Based on the cell fusion (4) and nuclear transfer …

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The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng Jan 2009

The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng

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Zinc is an essential cation for life that is involved in numerous physiology and pathophysiology processes. Despite its wide use as a cytoprotective agent in medications, its cellular and molecular mechanisms of action have not been well established. In order to define the potential therapeutic benefit of zinc, I used several Cystic Fibrosis (CF) and non-CF human airway epithelial cell lines as models in my studies. Extracellular zinc caused release calcium from the endoplasmic reticulum though zinc-sensitive Gq-coupled receptor(s) that may subsequently modulate ion channels. In addition, zinc also exhibited anti-inflammatory effects. Zinc inhibited pro-inflammatory molecular TNFα-induced cytokine and chemokine …

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Theoretical Context Of A Common Reproductive Health Behavior: Vaginal Douching Among A National Sample Of Young Adult Women, Disa Cornish Jan 2009

Theoretical Context Of A Common Reproductive Health Behavior: Vaginal Douching Among A National Sample Of Young Adult Women, Disa Cornish

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Current research suggests that up to 75% of American women have engaged in vaginal douching during their lives. Prevalence of the behavior is disproportionately high among minority women (especially African American) and women of low SES. Two bodies of research present conflicting results regarding the benefits or risks to reproductive health that are posed by vaginal douching, although the majority of research on this topic suggests that douching is associated with negative health outcomes. Although studies have suggested prevalence rates, behavioral correlates, and biological associations of vaginal douching, very few studies have used behavioral theory when examining the practice. The …

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Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck Jan 2009

Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck

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Capsule has been associated with virulence in numerous bacterial pathogens. The Mollicutes are a host-specific group of pathogens that cause a variety of economically relevant diseases important to man. Mycoplasma pneumoniae is responsible for 2 million cases of atypical pneumonia and 100,000 hospitalizations every year in the United States (Atkinson et al., 2008) (Krause and Taylor-Robinson, 1992). There was a toxic galactan molecule described as early as 1958 in Mycoplasma mycoides subsp. mycoides (Plackett and Buttery, 1958), although no evidence was presented that it was produced by the bacteria. Over the intervening fifty years the evidence to support the production …

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Biological Characterization Of Fc Receptor-Like 6 (Fcrl6), Daniel M. Schreeder Jan 2009

Biological Characterization Of Fc Receptor-Like 6 (Fcrl6), Daniel M. Schreeder

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Members of the Fc receptor-like (FCRL) family are cell-surface proteins with ancient conservation, distinct lymphocyte expression patterns, and tyrosine-based signaling capa-bilities that imply a fundamental role for them in modulating immune responses. Though they share many features with the Fc receptors (FCR) for IgG and IgE, FCRLs have not been found to bind immunoglobulin. In these studies, we sought to characterize the cellu-lar expression pattern, binding partner, and function of a recently identified FCRL family member, human FCRL6. By developing specific monoclonal antibodies (mAbs) we determined that FCRL6 is dis-tinctly expressed by cytotoxic lymphocytes, namely NK cells, CD8+ T cells, …

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