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Full-Text Articles in Medicine and Health Sciences
The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore
The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid beta plaques and neurofibrillary tangles, along with cognitive impairments that progress to dementia and eventually death. The development of drug treatments that rescue memory deficits could be a promising therapy given in the early stages of AD. In the following studies, we tested the potential for systemic treatment with histone deacetylase (HDAC) inhibitors to ameliorate cognitive deficits in a mouse model of AD. Using the APPSwe/PS1dE9 mouse model of AD, we showed that giving HDAC inhibitors systemically for 3 weeks reversed contextual memory deficits, stably maintained memories over a 2-week …
Modulation Of Intrinsic Activity In Sensory Cortex Facilitates Task Performance, Aburahman Elkhetali
Modulation Of Intrinsic Activity In Sensory Cortex Facilitates Task Performance, Aburahman Elkhetali
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Due to the changing demands of the environment and our behavioral intentions the brain has to adapt in order to produce task appropriate responses. Part of the challenge is the large amount of sensory information received by the brain. Depending on individu-al goals, the brain must select and react to task appropriate stimuli while ignoring other irrelevant sensory input. Since behavioral intentions are dynamic, this requires the re-sponses within the brain to also be dynamic. Cognitive control, exerted by higher centers on sensory cortex allow for selection of task relevant stimuli. In this study we find that intrinsic, non-stimulus driven …
The Role Of O-Glcnacylation In Synaptic Function, Erica Wynette Taylor
The Role Of O-Glcnacylation In Synaptic Function, Erica Wynette Taylor
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O-GlcNAcylation is a dynamic protein posttranslational modification that adds the monosaccharide ß-N-acetylglucosamine (GlcNAc) to specific serine and threonine residues on nucleocytoplasmic proteins. The hippocampus is a part of brain that has been shown to play a crucial role in learning and memory. Hippocampal neurons have high expression of O-GlcNAc transferase and O-GlcNAcase, which catalyze the addition and removal of GlcNAc from proteins respectively. Moreover, synaptic plasticity which is the strengthening or weakening of synaptic function on short- and long-term time scales is believed to be a cellular correlate of learning and memory. Several forms of synaptic plasticity have been characterized …
Role Of Kca3.1, A Calcium-Activated Potassium Channel, In Cell Migration In The Adult Brain, Kathryn L. Turner
Role Of Kca3.1, A Calcium-Activated Potassium Channel, In Cell Migration In The Adult Brain, Kathryn L. Turner
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A limited amount of migration occurs in the adult brain, including migration of neuroblasts during adult neurogenesis and pathological migration of primary brain tumors. Ion channels are commonly utilized during migration to allow shape and volume changes required for cell movement, and we specifically examine the role of KCa3.1 in the adult brain. These channels are well-suited to facilitate movement because they respond to common migration signals, i.e. intracellular Ca2+ changes, and efflux K+, allowing the outflow of water and cell volume regulation. Our findings suggest that KCa3.1 is highly expressed in migratory cells, adult neuroblasts and glioma cells, but …
The Role Of Pneumococcal Choline-Binding Protein A (Pcpa) In The Mechanism Of Virulence And Protective Immunity, Melissa Marie Walker
The Role Of Pneumococcal Choline-Binding Protein A (Pcpa) In The Mechanism Of Virulence And Protective Immunity, Melissa Marie Walker
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pcpA is under control of the Mn 2-dependent repressor PsaR. In the high manganese environment of mucosal sites pcpA gene expression is repressed and at the low manganese environment of the lung and blood derepression of pcpA gene expressionis observed. Previous data has shown that immunization of mice with rPcpA elicits protection against pneumonia and sepsis but had no effect on nasal colonization. We and others have shown that pcpA expression significantly enhances adherence of pneumococci to lung epithelial cell lines and although it is a virulence factor for pneumonia in mice there is no biologically relevant role for PcpA …
Anti-Group B Streptococci Monoclonal Antibodies Protect Against Invasive Aspergillosis, Rebekah Wharton
Anti-Group B Streptococci Monoclonal Antibodies Protect Against Invasive Aspergillosis, Rebekah Wharton
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Aspergillus fumigatus is a ubiquitous saprophytic fungus which can potentially cause life-threatening infections in immunocompromised individuals. Although a serious threat, current treatments are largely ineffective at reducing morbidity and mortality. To this end, we have characterized a monoclonal antibody generated against Group B Streptococci, type Ib, which also recognizes Aspergillus fumigatus conidia and hyphae. We show that this antibody appears to bind a similar epitope on both pathogens and provides a significant degree of protection in a murine model of invasive aspergillosis via a mechanism that appears to be dependent on complement. The studies we performed using this antibody should …
Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig
Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig
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SURVEYING THE SERUM PROTEOME FOR BIOMARKERS OF EARLY STAGE PANCREATIC CANCER MICHAEL ROBERT LUDWIG MICROBIOLOGY ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a uniformly fatal disease due to its refractory nature to conventional therapies at the time of initial diagnosis. In order to in-crease the curative potential of surgical resection, early detection of organ-confined neoplasia is needed. Currently, no effective diagnostic tools are available to detect early-stage pancreatic ductal lesions termed pancreatic intraepithelial neoplasia (PanIN) or lo-cally invasive, organ-confined disease. One way to identify biomarkers that may be use-ful for the early detection of PDAC is through the study of the …
The Phenotypic Expression Of Usp14 Deficiency Is Dependent Upon Genetic Background, Andrea Gail Marshall
The Phenotypic Expression Of Usp14 Deficiency Is Dependent Upon Genetic Background, Andrea Gail Marshall
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The ubiquitin proteasome system (UPS) plays a critical role in regulating a diversity of cellular processes that are essential to neuronal function, such as synaptic transmission, axon guidance, and neurite outgrowth. Dysfunctions of the UPS are linked with many neurodegenerative disorders, including motor neuron diseases like spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), although it is not known how UPS dysfunction contributes to disease pathology. The proteasome, an approximate 2.5 megadalton protein complex comprised of a 20S core particle and 19S regulatory particle, is the site of ubiquitin-mediated proteolysis in the cell. Recent studies have linked ubiquitin specific …
Epigenetic Regulation Of Kir4.1 In Normal And Pathological States: A Focus On Spinal Cord Injury, Sinifunanya Elvee Nwaobi
Epigenetic Regulation Of Kir4.1 In Normal And Pathological States: A Focus On Spinal Cord Injury, Sinifunanya Elvee Nwaobi
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Astrocytes are the most numerous cells in the brain and play a critical role in maintaining homeostatic extracellular potassium ([K+]e). This process is mediated, in part, by a glial-specific, inwardly rectifying potassium channel, Kir4.1. Pharmacological inhibition, knock down, or complete knock out of this channel results in astrocytes with increased membrane resistance, depolarized resting membrane potential, and altered extracellular potassium dynamics. Subsequent to the dysregulation of [K+]e, Kir4.1 knockout (KO) animals suffer from ataxia, seizures, and early postnatal death. Interestingly, Kir4.1 has long been characterized as a seizure susceptibility gene. The importance of Kir4.1 is further underscored by recent studies …
Understanding The Function And Regulation Of Eukaryotic Release Factor 1, Erf1, Sara Elisabeth Conard
Understanding The Function And Regulation Of Eukaryotic Release Factor 1, Erf1, Sara Elisabeth Conard
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Translation termination is an essential eukaryotic process that facilitates the end of protein synthesis and mediates the release of the nascent peptide chain. Two release factors, eRF1 and eRF3, with the help of a ribosome recycling factor assist in this process. eRF1 and eRF3 form a stable complex through conserved regions in their C-terminal domains. The eRF1/eRF3 complex, along with GTP, is absolutely vital for efficient termination in vitro and in vivo. The role of eRF1 during translation termination is to recognize the stop codon located in the ribosome aminoacyl site, stimulate GTP hydrolysis of eRF3 and enable peptide release …
Gabaergic Dysfunction In Huntington Disease, Sarah Elizabeth Dougherty
Gabaergic Dysfunction In Huntington Disease, Sarah Elizabeth Dougherty
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GABAergic neurons are responsible for regulation of neuronal signaling through inhibition. Alterations in the delicate balance of excitation and inhibition have been observed in many neurological disorders, including neurodegenerative diseases. Huntington disease (HD) is an autosomal dominant neurodegenerative disorder that is characterized by motor, psychiatric, and cognitive disturbances. As the hallmark movement pathology of HD is hyperkinesis it is intriguing to postulate that alterations in inhibition, and by extension within GABAergic cell networks, could be part of the pathogenesis of this disorder. In order to elucidate the role of GABAergic cell populations in HD we have used behavioral paradigms, molecular …
Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li
Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li
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Nonsteroidal anti-inflammatory drugs (NSAIDs) display promising antineoplastic activity for colorectal and other cancers, but toxicity from cyclooxygenase (COX) inhibition limits their long-term use for chemoprevention. However, many investigators have concluded that COX-independent mechanisms are responsible for their antineoplastic activity. We previously reported that cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) is a non-COX target of sulindac sulfide (SS). However, the specific isozyme families involved have not been well studied. Here we demonstrate that SS inhibits the growth of colon tumor cells through a novel mechanism involving inhibition of two cGMP degrading isozymes, PDE5 and PDE10, to activate cGMP-dependent protein kinase (PKG). …
Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah
Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah
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Fc receptors provide an interface between humoral immunity and cellular immunity by binding to the Fc portion of immunoglobulin and mediating effector functions. Cells expressing Fc receptors play a major role in immune complex clearance via phagocytosis, leading to a context dependent pro- or anti-inflammatory environment. Signaling by multi-chain Fc receptor complexes, including FcgRI, FcgRIII, FceRI and FcaRI is mediated by the ITAM-containing common FceRIg (g-chain) subunit. However, despite the use of a common g-chain, different Fc receptor complexes elicit specific cellular programs, suggesting additional layers of regulation of tyrosine based signaling by g-chain. We hypothesized that the unique g-chain …
The Role Of Palmitoylation And Other Post-Translational Modifications In Cftr Biogenesis, Michelle Mcclure
The Role Of Palmitoylation And Other Post-Translational Modifications In Cftr Biogenesis, Michelle Mcclure
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Post-translational modifications (PTMs) are important contributors to protein bio-genesis and function. CFTR in particular is known to be regulated by multiple PTMs, in-cluding glycosylation, phosphorylation, and ubiquitination. The functional significance and specific CFTR residues responsible for the majority of PTMs within CFTR are not known. The goal of this dissertation was to identify and characterize novel PTMs that influence wild-type and F508del CFTR. The study employed a combination of tandem and multiple reaction ion monitoring mass spectrometry to identify covalent side chain attachments. Analysis revealed the specific locations of numerous phosphorylated resi-dues, several sites of methylation, and more than twenty-five …
The Development Of An In Vitro Surrogate Assay For Screening Protective Antibodies Against Pneumococcal Surface Protein A (Pspa), Kristopher Ruben Genschmer
The Development Of An In Vitro Surrogate Assay For Screening Protective Antibodies Against Pneumococcal Surface Protein A (Pspa), Kristopher Ruben Genschmer
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PCV13 is the current pneumococcal protein conjugated vaccine made up of the 13 most clinically relevant capsular polysaccharides. While protective, it is limited to a small portion of the overall serotypes of Streptococcus pneumoniae. The possibility of "serotype replacement" by serotypes not covered by the vaccine and the high cost of producing this conjugated polysaccharide vaccine stress the need for a protein based vaccine, one that is more broad in its protection. Pneumococcal surface protein A (PspA) has been shown to be both immunogenic and protective in mice and is a promising protein vaccine candidate. However, there are no current …
The Role Of Gadd45b In Hippocampus-Dependent Cognition, Synaptic Plasticity And Activity-Associated Transcriptional Dynamics, Faraz Sultan
The Role Of Gadd45b In Hippocampus-Dependent Cognition, Synaptic Plasticity And Activity-Associated Transcriptional Dynamics, Faraz Sultan
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An expanding body of literature argues for a pivotal role of molecular epigenetic mechanisms in memory. Defined as mechanisms that regulate gene expression in the absence of DNA sequence modifications, these regulate various stages of memory-associated transcription. These phenomena are present at diverse anatomical subregions of the central nervous system (CNS) and regulate corresponding behaviors. Epigenetic mechanisms comprise a unique category of behavioral and physiological modulators because of their potential to modify the cellular phenotype in a stable manner. Hence, epigenetics offers a novel potential solution to a central paradox in memory retention: the finding that most putative molecular substrates …
Potential Roles Of The Immunostimulatory Signals Il-15 And Mica In Oncolytic Hsv-1 Therapy For Malignant Glioma, David Curtis Gaston
Potential Roles Of The Immunostimulatory Signals Il-15 And Mica In Oncolytic Hsv-1 Therapy For Malignant Glioma, David Curtis Gaston
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Malignant gliomas are the most frequently diagnosed and the most fatal primary brain tumors. Innovative therapeutic approaches are necessary to combat these devastating cancers, and oncolytic herpes simplex virus type-1 (oHSV) deleted of the γ134.5 neurovirulence gene is a promising adjunctive therapy. The primary mechanism of tumor clearance by oHSV is lytic replication specifically within malignant cells. oHSV also stimulates tumor infiltration of cytotoxic immune effector cells that can participate in tumor clearance. However, cytotoxic immune cells target oHSV as well as tumor, which may limit therapeutic efficacy. Further knowledge regarding the nature of these interactions and how the interactions …
Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar
Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar
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Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac sulfide (SS) have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from cyclooxygenase (COX) inhibition limit their use in cancer prevention. We recently described a N,N-dimethylethyl amine derivative of SS, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth inhibitory activity. Here, we studied the basis for the growth inhibitory effects of SSA on human lung adenocarcinoma cell lines and evaluated its preclinical pharmacology. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2-5 μ compared with 44-52 …
Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs
Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs
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ABSTRACT Multiple Myeloma (MM) remains the second most common hematologic malig-nancy occurring in adults, which primarily affects the skeletal system causing severe bone destruction, spinal cord compression and hypercalcemia. Current therapies, which include chemotherapy, radiotherapy, autologouos stem cell transplantation and in some cases surgery, have extended the median survival between 3 and 10 years. However, MM is still incurable and therefore improving current therapies or developing newer ones to reduce the burden of osteolytic damage and extend survival rate will be highly beneficial for patient management. The long-term goal of this study is to develop a novel therapeutic approach to …
Genetic And Biochemical Characterizations Of The Capsular Glycosyltransferases In Streptococcus Pneumoniae Serotype 2, David Boyd Anthony James
Genetic And Biochemical Characterizations Of The Capsular Glycosyltransferases In Streptococcus Pneumoniae Serotype 2, David Boyd Anthony James
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The principle objective of this dissertation is to develop a thorough understanding of the genetics and biochemistry of capsule synthesis. Specifically, it involves the identification and characterization of the capsular glycosyltransferases in Streptococcus pneumoniae serotype 2, with investigations into their regulation. S. pneumoniae (the pneumococcus) is a significant human pathogen that has the ability to persist as a commensal and then transition to a virulent state, the latter of which is a major contributor to global morbidity and mortality. The capsular polysaccharide (CPS) of S. pneumoniae is a protective surface structure that plays an integral role in this disease process. …
Intracellular Quantitation And Pharmacokinetic Modeling Of Nucleoside Analogs In The Female Genital Tract, Amanda Marie James
Intracellular Quantitation And Pharmacokinetic Modeling Of Nucleoside Analogs In The Female Genital Tract, Amanda Marie James
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Human Immunodeficiency Virus (HIV) is one of the leading infectious diseases in the world. In spite of substantial progress in the advancement of antiretroviral therapy for HIV treatment, new infections outpace the number of infected persons initiating ART. Therefore, the prevention of HIV remains a crucial health issue. Pre-Exposure Prophylaxis, (PrEP), which involves using one or more antiretroviral agents to reduce the risk of HIV infection prior to potential exposure, has shown effectiveness at reducing HIV transmission in study volunteers with different sexual orientation around the world. The clinical pharmacology of antiretroviral drugs, specifically tenofovir (TFV) and emtricitabine (FTC), in …
Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe
Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe
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Glioblastoma multiforme (GBM) is the most common and deadly primary brain malignancy necessitating improved understanding of GBM biology. In this study, we explore the role of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS) in the context of GBM. We have discovered that the MARCKS protein regulates GBM growth as well as response to radiation therapy through its effects on proliferation, senescence, and DNA repair based on our studies in cell culture and in patient-derived xenograft tumors implanted in mice. Importantly, our analysis of clinical patient data demonstrates that MARCKS is an independent predictor for outcome in GBM patients. Indeed, high MARCKS …
Usp49 And H2b Deubiquitination In Chromatin And Cellular Function, Amanda E. Jones
Usp49 And H2b Deubiquitination In Chromatin And Cellular Function, Amanda E. Jones
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Histones are globular proteins which help package and organize DNA in the eukaryotic nucleus. The four core histones, H2A, H2B, H3 and H4, combine with approximately 146 base pairs of DNA to form a nucleosome, the fundamental unit of chromatin. Post-translational modifications to the C-terminal and N-terminal histone tails regulate chromatin structure and function, and play important roles in transcriptional regulation, replication, DNA damage response, and mRNA processing. Histone H2B ubiquitination is an evolutionarily conserved modification with roles in gene expression and DNA damage repair. In addition, H2B ubiquitination may also regulate mRNA splicing. Here, we identify USP49, a cysteine …
Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi
Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi
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Basal-like breast cancers (BLBC) display aggressive clinical behavior attributed to the presence of cancer stem cells (CSCs). TRA-8, a monoclonal antibody that binds specifically to TRAIL death receptor 5, preferentially induces apoptosis in BLBC subtype cells; however it is unknown if TRA-8 is also cytotoxic to the CSC population. Moreover, some BLBC cell lines are resistant to TRA-8, and overcoming resistance is critical for clinical translation of this therapy. One potential approach to overcome TRA- 8 resistance is to target the Wnt/ß-catenin pathway. LRP6 is a cell surface receptor that is an indispensable element of the Wnt/ß-catenin signaling pathway that …
Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy
Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy
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The molecular mechanisms regulating the preferential metastasis of breast cancer to bone have not been fully elucidated, but it is hypothesized that local conditions in the bone create an environment conducive to colonization by breast cancer cells and that the breast cancer cells interact directly with cells in the bone. In this dissertation, two goals were pursued: (1) to explore breast cancer secreted interleukin (IL)-11's role on osteoclast function and (2) investigate the expression and potential role of CD68 in breast cancer adhesion to bone. Higher rates of bone metastasis occur in human breast cancer tumors expressing IL-11, a cytokine …
Phenotypic Analysis Of B Cells In Hla*B44 Positive Patients That Exhibit Common Variable Immunodeficiency And Recurrent Sino-Pulmonary Infections, Eva Szymanska Mroczek
Phenotypic Analysis Of B Cells In Hla*B44 Positive Patients That Exhibit Common Variable Immunodeficiency And Recurrent Sino-Pulmonary Infections, Eva Szymanska Mroczek
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Depressed serum immunoglobulin levels and recurrent sinopulmonary infections mark Common Variable Immune Deficiency (CVID). Many family members of CVID patients also suffer Recurrent Sino-Pulmonary Infection (RESPI) but have normal serum immunoglobulins. We identified HLAB44 positive identical female twins who suffer sinopulmonary infections and are discordant for CVID and RESPI. Flow cytometry subsets showed equivalent numbers of immature B cells (BC) in both twins, but lower numbers of transitional and mature BC in the CVID twin. Presented is an in-depth comparison of V (D) J gene usage, hydrophobicity, length, DH reading frame, and amino acid usage between µ H chain repertoires …
Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson
Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson
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Pathological hallmarks of AD include neurofibrillary tau tangles, amyloid beta (Abeta) accumulation and cholinergic degeneration. Cholinergic degeneration can be mimicked in rats by lesioning cholinergic neurons in medial septum. Hippocampal cholinergic denervation disrupts retrograde transport of nerve growth factor (NGF), leading to its accumulation, which subsequently triggers sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. Dr. McMahon's lab previously reported that coincident with this sprouting, there is an increase in cholinergic innervation that correlates with a recovery of M1 muscarinic receptor dependent plasticity at CA3-CA1 synapses and visual cortex. These findings suggest that noradrenergic sympathetic sprouting …
Microevolution Of Capsule Synthesis Genes Contributes To Pneumococcal Capsule Diversity, Melissa Beth Oliver
Microevolution Of Capsule Synthesis Genes Contributes To Pneumococcal Capsule Diversity, Melissa Beth Oliver
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Streptococcus pneumoniae (pneumococcus) is an important human pathogen that expresses a capsular polysaccharide (PS) to shield underlying antigenic structures from complement-mediated opsonophagocytosis. Thus, capsular PS is the major virulence factor, the target of primary immune responses to pneumococcal infections, and the antigenic component of pneumococcal vaccines. Pneumococci have diverse capsular PS synthesis (cps) loci and express over 90 different capsule types. Such diversity helps pneumococci escape immune detection and adapt to changing environments. Recombination of cps genes has been recognized as the main driver of capsule diversity. However, we show point mutations in cps genes encoding glycosyltransferases can broaden enzymes' …
Regulation Of Stim1 By O-Glcnacylation In Cardiomyocytes, Xiaoyuan Zhu-Mauldin
Regulation Of Stim1 By O-Glcnacylation In Cardiomyocytes, Xiaoyuan Zhu-Mauldin
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In non-excitable cells, STIM1 and Orai1 are the primary mediators of store-operated Ca2+ entry (SOCE); however little is known about their roles in cardiomyocyte Ca2+ handling. We have previously shown that acute increases in the levels of O-GlcNAcylation (the attachment of O-linked N- acetylglucosamine (O-GlcNAc) to target proteins) are cardioprotective through attenuating Ca2+-mediated injury and increased O-GlcNAcylation blunts SOCE in cardiomyocytes. Therefore, the goals here were to determine the regulation of STIM1 and STIM1-mediated SOCE by O-GlcNAcylation in cardiomyocytes. Immunohistochemical analysis demonstrated the co-localization of STIM1 with SERCA and RyR in adult cardiomyocytes. NRVMs were transfected with the eYFP-tagged STIM1 …
The Genetic Complexity Of The Human Fc-Gamma Receptor 1q23 Locus And Its Relationship To Autoimmunity, Travis Samuel Ptacek
The Genetic Complexity Of The Human Fc-Gamma Receptor 1q23 Locus And Its Relationship To Autoimmunity, Travis Samuel Ptacek
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The human immune system must be able to adapt to a wide spectrum of invading pathogens in order to keep the human body alive. This variation includes directed recombination and mutation at the level of the individual and genetic variation and natural selection at the population level. A direct consequence of the adaptability of the immune system is autoimmunity: as the immune system adapts to a shifting spectrum of antigens, it can shift to self-antigens, and therefore attack the body and cause disease. Since genetic factors are part of this adaptability, they are also connected with autoimmune disease. SLE is …