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Full-Text Articles in Medicine and Health Sciences
Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover
Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover
All ETDs from UAB
Selective serotonin reuptake inhibitors (SSRIs) have been a mainstay pharmacological treatment for women experiencing depression during pregnancy and postpartum for nearly three decades. Recently, though, growing evidence indicates that early-life SSRI exposure triggers long-lasting behavioral abnormalities. Clinically, children exposed to SSRIs in early life exhibit increased internalizing behavior, reduced social behavior, and increased risk for depression in adolescence. Similarly, in rodents, perinatal SSRI exposure leads to increased traits of anxiety- and depression-like behavior. Interestingly, certain individuals are more susceptible to early-life SSRI exposure than others, suggesting that perinatal SSRI exposure poses greater risks for negative outcome within certain populations; however, …
The Matricellular Protein Ccn1 Potentiates Fibrogenic Responses To Lung Injury, Ashish Kurundkar
The Matricellular Protein Ccn1 Potentiates Fibrogenic Responses To Lung Injury, Ashish Kurundkar
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Normal wound healing is a well-coordinated reparative response to injury aimed at restoring the normal tissue function. The dynamic interactions between cells and ex-tracellular matrix (ECM) regulate and dictate the fate of tissue repair process. Fibrosis is a dysregulated wound healing with excessive deposition of ECM and loss of tissue func-tion. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic disease of lung with no cure. Matricellular proteins are non-structural matrix proteins which regulates the cellular functions by directly binding to cell surface integrins and/or indirectly modulating growth factor signaling. Matricellular proteins are emerging as critical mediators of tissue injury …
14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley
14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley
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Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of inherited Parkinson’s disease (PD), and LRRK2 is a risk factor for idiopathic PD. How LRRK2 function is regulated is not well understood. Recently, the highly-conserved 14-3-3 proteins, which play a key role in many cellular functions including cell death, have been shown to interact with LRRK2. In this study, we investigated whether 14-3-3s can regulate mutant LRRK2-induced neurite shortening and kinase activity. In the presence of 14-3-3θ overexpression, neurite length of primary neurons from BAC transgenic G2019S-LRRK2 mice returned back to wildtype levels. Similarly, 14-3-3θ overexpression …
Exploring Bacteriophage P22 As A Selective Molecular Scaffold And Molecular Sensor, Gregory Joseph Bedwell
Exploring Bacteriophage P22 As A Selective Molecular Scaffold And Molecular Sensor, Gregory Joseph Bedwell
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The virus capsids of many dsDNA bacteriophage are finely tuned macromolecular machines. Their functionality begins at assembly, when their capsids are built under the guidance of a class of proteins referred to as scaffolding proteins. The scaffolding protein of bacteriophage P22 is a flexible, highly elongated protein that binds to the interior surface of the P22 procapsid via its C-terminal domain. The finding that N-terminus is dispensable for procapsid binding prompted the development of chimeric scaffolding protein molecules, wherein N-terminal residues of scaffold are replaced with a variety of different peptide sequences or functional proteins that are then encapsidated within …
Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer
Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer
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Overcoming cancer cell immune escape represents a fundamental obstacle in the treatment of cancer. Indoleamine 2,3-dioxygenase (IDO)-expressing myeloid-derived suppressor cells (MDSCs) are known to induce oxidative stress and alter amino acid metabolism within the tumor microenvironment (TME). The tryptophan (Trp)-catabolizing action of IDO not only promotes T cell tolerance and evasion but is also associated with impaired quality of life in cancer patients. We have previously demonstrated that a novel combination therapy, consisting of MDSC-depleting gemcitabine and a superoxide dismutase mimetic, prolonged survival of tumor-bearing mice by enhancing CD8+ memory T cell metabolism. We identify that combination therapy inhibits IDO …
The Role Of Glutamate In Immune Cell Infiltration And Excitotoxic Mechanisms In Autoimmune Demyelination, Kirsten Scarlett Evonuk
The Role Of Glutamate In Immune Cell Infiltration And Excitotoxic Mechanisms In Autoimmune Demyelination, Kirsten Scarlett Evonuk
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Multiple sclerosis is the most common neurological disorder in young adults. Current treatments modulate the immune system, but no treatments prevent central nervous system damage. Inflammation occurs even during disease remission, contributing to ongoing damage and resulting in disease progression. The lack of neuroprotective treatments despite continued inflammatory onslaught in the central nervous system indicates the need for therapeutic discovery in this area. One potential therapeutic target is glutamate, whose dysregulation in multiple sclerosis has been implicated in excitotoxic cellular death. Herein we describe the roles of glutamate in multiple sclerosis and explore the blockade of a source of excitotoxic …
Role Of Autocrine And Paracrine Wnt Signaling In Chronic Myeloid Leukemia Stem Cells, Puneet Agarwal
Role Of Autocrine And Paracrine Wnt Signaling In Chronic Myeloid Leukemia Stem Cells, Puneet Agarwal
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Treatment of chronic myeloid leukemia (CML) with BCR-ABL tyrosine kinase inhibitors (TKIs) fails to eradicate the leukemia stem cells (LSCs) from which the disease arises. Previously, we and others have shown that LSC persistence is related to kinase-independent mechanisms and mediated in part by signals from the bone marrow microenvironment (BMM). Specifically, we found that WNT signaling from the BMM may contribute to preservation of CML LSC following TKI treatment. Wnt secretion and activity requires their palmitoylation by the Porcupine acyltransferase (PORCN). WNT974 (formerly LGK974) is a potent PORCN inhibitor that blocks WNT signaling and demonstrates in vivo efficacy against …
Structure-Function Relationships In The Sec7 Guanine Nucleotide Exchange Factor Gbf1, Jay Manoj Bhatt
Structure-Function Relationships In The Sec7 Guanine Nucleotide Exchange Factor Gbf1, Jay Manoj Bhatt
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All eukaryotic cells contain a secretory pathway composed of membrane-bound compartments connected by vesicles that transport cargo from the endoplasmic reticulum (ER) through the Golgi apparatus to various destination within and outside the cell. The Golgi Brefeldin A-resistant Factor 1 (GBF1) is required for protein traffic between ER and Golgi and within the Golgi. GBF1 belongs to a family of Guanine nucleotide Exchange Factors (GEFs) that stimulate the nucleotide exchange of GDP for GTP on small GTPases called ADP-ribosylation factors (ARFs). Once GTP-bound, ARFs become active and initiate a cascade of events that lead to vesicle formation. Thus, GBF1 is …
Behavioral And Developmental Abnormalities In Sult4a1 Deficient Zebrafish, Francis Crittenden
Behavioral And Developmental Abnormalities In Sult4a1 Deficient Zebrafish, Francis Crittenden
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Since its identification in 2000, sulfotransferase (SULT) 4A1 has presented an enigma to the field of cytosolic SULT biology. SULT4A1 is exclusively expressed in neural tissue, is highly conserved, and has been identified in every vertebrate studied to date. Despite this singular level of conservation, no substrate or function for SULT4A1 has been identified. Previous studies demonstrated that SULT4A1 does not bind the obligate sulfate donor, 3’-phosphoadenosine-5’-phosphosulfate (PAPS), yet SULT4A1 is classified as a SULT superfamily member based on sequence and structural similarities to the other SULTs. In this study, RNA-seq was used to search for alterations in gene ex-pression …
The Role Of Mammalian Tribbles Homolog 3 (Trb3) In Macrophage Biology; Evidence For Reciprocal Regulation Of Macrophage Function In Foam Cell Formation, Dennis Steverson
The Role Of Mammalian Tribbles Homolog 3 (Trb3) In Macrophage Biology; Evidence For Reciprocal Regulation Of Macrophage Function In Foam Cell Formation, Dennis Steverson
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Atherosclerosis is disease characterized by dysregulated lipid metabolism and chronic inflammation. Macrophages are critical to the progression of the disease and are involved in the pathophysiology at all stages of the disease. In the early stages, macrophages are responsible for fatty streak formation by becoming foam cells through lipid uptake. In the later stages, macrophages contribute to the degradation of the fibrous cap and are largely responsible for chronic inflammation in atherosclerotic plaques. Tribbles homolog 3 (TRB3) is a pseudokinase that inhibits Akt activation by blocking its phosphorylation site. TRB3 is expressed on numerous cell types in the body (pancreatic …
Human Cytosolic Sulfotransferase (Sult) 1b1 Half-Site Reactivity And The Identification And Characterization Of A Novel Variant Sult1b1 Isoform (L145v), Zachary Evan Tibbs
Human Cytosolic Sulfotransferase (Sult) 1b1 Half-Site Reactivity And The Identification And Characterization Of A Novel Variant Sult1b1 Isoform (L145v), Zachary Evan Tibbs
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The human cytosolic sulfotransferases (hSULTs) are a fourteen-member family of phase II drug-metabolizing enzymes that catalyze the transfer of a sulfonate moiety from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to a recipient substrate. SULT-mediated sulfation serves to deactivate physiological hormones and detoxify xenobiotics. SULT1B1 is primarily resident to the gastrointestinal tract, liver, and possibly peripheral white blood cells (WBCs), whereby it performs its supposed physiological role. The iso-form has the capacity to sulfate thyroid hormones, small phenols, and polyaromatic hy-drocarbons resulting in their inactivation, detoxification, and bioactivation/detoxification, respectively. Immunohistochemistry was used to show hSULT1B1 protein is present in periph-eral lymphocytes and neutrophils. Further, …
Germline Restriction Of B Cell Receptor Repertoire Influences Antigenic Epitope Recognition And Primary Antibody Deficiency Pathogenesis, Yuge Wang
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Part I. Mouse Studies Complementarity determining region 3 of the immunoglobulin (Ig) H chain (CDR-H3) lies at the center of the antigen binding site where it often plays a decisive role in antigen recognition and binding. Amino acids encoded by the diversity (DH) gene segment are the main component of CDR-H3. Each DH has the potential to rearrange into one of six DH reading frames (RFs), each of which exhibits a characteristic amino acid hydrophobicity signature that has been conserved among jawed vertebrates by natural selection. A preference for use of RF1 promotes the incorporation of tyrosine into CDR-H3 while …
Epigenetic Dysregulation In Levodopa-Induced Dyskinesia, David Anthony Figge
Epigenetic Dysregulation In Levodopa-Induced Dyskinesia, David Anthony Figge
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Levodopa-induced dyskinesia (LID) is a persistent behavioral sensitization that develops after repeated levodopa (L-DOPA) exposure in Parkinson disease (PD) patients. LID is characterized by a “priming effect”, whereby initial administrations of L-DOPA trigger a sensitized biochemical and transcriptional response upon subsequent administrations of L-DOPA. In neurons, transcriptional regulation through dynamic changes to epigenetic modifications, including DNA methylation and histone acetylation, have been shown pivotal to many long-term behavioral modifications; however, their role in LID has been minimally explored. Using a rodent model, we show LID development leads to the aberrant expression of DNA demethylating enzymes and locus-specific changes to DNA …
The Role Of Hydrogen Peroxide In The Modulation Of Capsule Biosynthesis In Streptococcus Pneumoniae Serotype 2, Jocelyn Renee Hauser
The Role Of Hydrogen Peroxide In The Modulation Of Capsule Biosynthesis In Streptococcus Pneumoniae Serotype 2, Jocelyn Renee Hauser
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Streptococcus pneumoniae is a gram-positive bacterial pathogen that causes diseases such as pneumonia, meningitis, bacteremia and middle ear infections. The major virulence factor of S. pneumoniae is its polysaccharide capsule. The capsule enables the organism to evade host defenses by providing protection against complement-mediated opsonophagocytosis in systemic sites and by allowing the organism to successfully colonize the nasopharynx. The nasopharynx is the natural reservoir of S. pneumoniae. In the nasopharynx, S. pneumoniae is in a high oxygen (O2) environment, however when it has the opportunity to bypass host defenses and invade systemic sites, it reaches environments with low O2. Capsule …
Early-Life Programming Of Emotional Behaviors And Cardiovascular Function, Samir Rana
Early-Life Programming Of Emotional Behaviors And Cardiovascular Function, Samir Rana
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Extensive evidence implicates bi-directional relationship between mood disorders and cardiovascular disorders. Early-life experience can have strong effects both on emotional development and cardiovascular function throughout life. Studies in humans are limited to correlational analyses, which are necessarily limited in terms of revealing mechanistic underpinnings of these associations. Thus, various pre-clinical models are utilized to investigate the effects of early-life experience in various domains, such as behavior and cardiovascular function, which are likely mediated by epigenetic mechanisms. Previous studies have used maternal separation and neonatal handling in developing rodents as a way to model differences in early-life experience. The effect of …
Reorganization Of The Golgi Apparatus During Human Cytomegalovirus Infection, George Michael Rebmann
Reorganization Of The Golgi Apparatus During Human Cytomegalovirus Infection, George Michael Rebmann
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Human cytomegalovirus (HCMV) is the largest and most structurally complex of all the herpesviruses. HCMV is an important human pathogen that results in significant morbidity and disease in immunocompromised individuals. The assembly of herpesviruses is complex and involves a nuclear and cytoplasmic phase. The nuclear events of capsid assembly and genome incorporation as well as nuclear egress are believed to be similar in all herpesviruses and as such, are more clearly defined then the cytoplasmic phase; including the process of tegument and envelope acquisition. Human Cytomegalovirus induces the reorganization of the cellular secretory pathway including the Golgi apparatus and membranes …
The Effect Of Proinflammatory Cytokines On Thioredoxin-Interacting Protein In Pancreatic Beta-Cells, Kyunghee Hong
The Effect Of Proinflammatory Cytokines On Thioredoxin-Interacting Protein In Pancreatic Beta-Cells, Kyunghee Hong
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Pro-inflammatory cytokines, such as Interleukin (IL)-1β, Tumor necrosis factors (TNF) α, and Interferon (IFN)γ, have been implicated as critical mediators of β-cell destruction in diabetes. In addition, although a combination of these three cytokines has been used to mimic the inflammatory conditions of type 1 diabetes in vitro, the mechanisms underlying the effect are not fully understood. Previously, we discovered Thioredoxin-interacting protein (TXNIP) as a key regulator of glucotoxicity-induced β-cell apoptosis and β-cell dysfunction, while deletion of TXNIP prevented type 1 (T1D) and type 2 diabetes (T2D). However, the effects of proinflammatory cytokines on the regulation of TXNIP have not …
Motor Unit Remodeling During Neuromuscular Degeneration In Aging And Parkinson's Disease, Neil Anthony Kelly
Motor Unit Remodeling During Neuromuscular Degeneration In Aging And Parkinson's Disease, Neil Anthony Kelly
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The human neuromuscular system deteriorates progressively with age and disease. This results in denervation events and ultimately motor unit remodeling, which is revealed by abnormal “groups” of myofibers expressing the same myosin protein isoform – a phenomenon described as myofiber type grouping. Despite the acceptance of myofiber type grouping as a hallmark indicator of motor unit remodeling, traditional techniques of detecting it lack quantitative parameters and therefore comparative data in aging and disease are scarce. The purpose of this dissertation is to establish a statistically-driven, quantitative method for detecting myofiber type grouping and to use it to characterize the effects …
Regulation Of Breast Cancer Metastasis By Sin3 Chromatin Remodeling Complexes, Monica Jeanene Lewis
Regulation Of Breast Cancer Metastasis By Sin3 Chromatin Remodeling Complexes, Monica Jeanene Lewis
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Metastasis continues to be the most difficult clinical challenge for breast cancer. Survival rates for patients with metastatic breast cancer have not significantly changed in the past 20 years. Therefore, we need a better understanding of the molecular mechanisms that regulate breast cancer metastasis to develop effective therapies. SIN3 chromatin remodeling complexes have been implicated in breast cancer progression. Mammalian cells have two paralogs of SIN3 (SIN3A and SIN3B) that are encoded by distinct genes and have unique functions during development. However, specific roles for SIN3A and SIN3B in breast cancer progression have not been characterized. To better understand how …
Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu
Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu
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Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson disease (PD) , with pathogenic mutations located within each of the two catalytic cores of the protein, the GTPase and kinase domains. The most prevalent pathogenic mutation, G2019S increases kinase activity up to 5-fold, causing significant changes in the protein’s biochemical behavior. Other mutations such as R1441G and I2020T have also been demonstrated to increase LRRK2 kinase activity, however, the detailed mechanisms remains unclear. A major limitation in the field is the lack of structural information of LRRK2. This dissertation detailed …
Structural Basis For Lipid-And Calmodulin-Mediated Akt Activation In Breast Cancer Cells, Constance Agamasu
Structural Basis For Lipid-And Calmodulin-Mediated Akt Activation In Breast Cancer Cells, Constance Agamasu
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Growth and survival signals initiated at the cell surface by receptor-ligand interactions often involve a downstream activation of Akt, a serine/threonine kinase critical in regulating cell survival, apoptosis and oncogenesis. Hyper-activation of Akt is a common tumorigenic event, thereby making the Akt activation pathway a prime target for cancer therapy. The translocation of Akt to the plasma membrane (PM) for phosphorylation is a critical step in the Akt activation pathway. It has been established that membrane binding of Akt is mediated by direct interactions between its pleckstrin homology domain (PHD) and membrane lipid phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3]. There is now emerging …
Regulation Of Vibrio Cholerae Biofilm Formation By H-Ns Repression And Anti-Repression, Julio Cesar Ayala-Figueredo
Regulation Of Vibrio Cholerae Biofilm Formation By H-Ns Repression And Anti-Repression, Julio Cesar Ayala-Figueredo
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The diarrheal disease cholera is caused by the Gram-negative and motile bacterium Vibrio cholerae of serogroups O1 and O139. V. cholerae can switch between planktonic (motile) and sessile (biofilm) lifestyles. Biofilms are sessile communities encased in a self-produced extracellular matrix mainly composed of exopolysaccharide, proteins and extracellular DNA. Biofilm formation enhances the capacity of V. cholerae to persist in environmental waters and increases its infectivity. The bacterial second messenger cyclic diguanylic acid (c-di-GMP) regulates the transition between motile and biofilm lifestyles in V. cholerae. At low cell density, two c-di-GMP receptors, the LuxR-type regulator VpsT and the NtrC-type regulator VpsR …
Cell Signaling Pathways As Targets For Precision Medicine In Head And Neck Squamous Cell Carcinoma, Alice Weaver
Cell Signaling Pathways As Targets For Precision Medicine In Head And Neck Squamous Cell Carcinoma, Alice Weaver
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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high rates of recurrence and mortality. Unlike other cancer types, genome sequencing studies have failed to produce clinically actionable targets to improve HNSCC management. Therefore, alternative methods are needed to study the molecular mechanisms responsible for disease progression and response to therapy. The focus of this research was to determine how dysregulation of cell signaling pathways affects outcomes in HNSCC. In HPV-positive HNSCCs, we hypothesized that HPV induces dysregulation of the DNA damage response which mediates differences in therapeutic sensitivity and survival. We identified a defect in DNA …
Interplay Between Her2, Parp1, And Nf-Κb In Breast Cancer: Potential Therapeutic Implications, Monicka Ewa Wielgos
Interplay Between Her2, Parp1, And Nf-Κb In Breast Cancer: Potential Therapeutic Implications, Monicka Ewa Wielgos
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We previously reported that HER2+ breast cancers are susceptible to Poly (ADP-Ribose) polymerase inhibitors (PARPi) alone, agents that are efficacious against homologous recombination (HR) deficient tumors. However, this phenomenon was determined to be independent of a HR repair deficiency but rather due to suppression of NF-κB activity and signaling by PARP inhibition. Further, HER2 overexpression itself was necessary and sufficient to confer this susceptibility. Interestingly, PARP1 and phosphorylated RelA/p65 (NF-κB) levels were found to be elevated in human HER2+ breast cancers compared to luminal breast cancers. These data suggest a possible interplay between HER2, PARP1, and NF-κB, and how this …
The Impact Of Rrna And Trna Synthesis On Chromatin Structure And Cell Fate, Jessica Makofske Woolnough
The Impact Of Rrna And Trna Synthesis On Chromatin Structure And Cell Fate, Jessica Makofske Woolnough
All ETDs from UAB
The Central Dogma of molecular biology describes the process by which genetic material is faithfully converted into functional molecules across all domains of life. Originally, RNA was solely understood as an intermediate in this process. However, mounting evidence over the past 50 years has made clear that RNA have diverse functional roles as a class of molecule termed non-coding RNA. Two of the first described non-coding RNA have essential roles within the Central Dogma, itself: ribosomal RNA (rRNA) and transfer RNA (tRNA). These two non-coding RNA are highly abundant, collectively accounting for up to 90% of the total transcript in …
Ribosomal Protein L12 (Rpl12) As A Novel Target In Cystic Fibrosis, Kathryn E. Oliver
Ribosomal Protein L12 (Rpl12) As A Novel Target In Cystic Fibrosis, Kathryn E. Oliver
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Approximately 1,000 new cases of cystic fibrosis (CF) are diagnosed in the United States every year. The disease is caused by over 1,700 naturally occurring variants in the CF transmembrane conductance regulator (CFTR). Defects in the CFTR coding sequence contribute to variable disease severity in the patient population. The majority of individuals born with CF harbor at least one specific mutation in CFTR termed F508del. Clinical manifestations of CF include severe damage of multiple exocrine tissues, including the lungs, intestine, pancreas, reproductive and other organ systems. An overarching goal of our work is to identify cellular targets that contribute to …
Cd4 Regulatory T Cells Augment Hiv-1 Expression Of Polarized M1 And M2 Monocyte Derived Macrophages, Tanya Robinson
Cd4 Regulatory T Cells Augment Hiv-1 Expression Of Polarized M1 And M2 Monocyte Derived Macrophages, Tanya Robinson
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Polarization of macrophages is critical for an effective host immune response against invading pathogens. However, the HIV-1 virus can alter the cytokine/chemokine profile of polarized macrophages which may ultimately lead to their increased susceptibility to viral infection. M1 monocyte-derived macrophages (MDM) have been shown to suppress CCR5-tropic HIV-1 replication, while M2 MDM promote it. We generated M1 (GM-CSF + IFN-γ + LPS) and M2 (M-CSF + IL-4) MDM with predicted phenotypes and exposed them to a CCR5 (R5) “highly macrophage-tropic” viral strain, HIV-1BaL. M2 MDM had notably higher levels of HIV-1 infection than M1 MDM. We also investigated R5 HIV-1 …
Regulation Of The Mitochondrial Thiol Network With Targeted Electrohpiles, Matthew Ryan Smith
Regulation Of The Mitochondrial Thiol Network With Targeted Electrohpiles, Matthew Ryan Smith
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Cells possess a remarkable plasticity to alter their metabolism and change their function based on stimuli within their resident microenvironment. The mitochondria within these cells utilize a variety of sources such as pyruvate, glutamine, or fatty acids in order to generate metabolites, amino acids, and reducing equivalents needed for cellular proliferation.Many mitochondrial enzymes possess contain a cysteine which possesses a thiol group, a unique redox-signaling moiety that can be activated under specific circumstances by bio-reactive compounds forming a network of mitochondrial proteins which are responsible for mitochondrial respiration. However, it is unknown whether targeting these reactive thiol groups present a …
Analysis Of The Ciliary Genes Gas8 And Mks6 Reveal Conserved Roles In Cilia Motility And Transition Zone Function, Wesley Robert Lewis
Analysis Of The Ciliary Genes Gas8 And Mks6 Reveal Conserved Roles In Cilia Motility And Transition Zone Function, Wesley Robert Lewis
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Cilia are microtubule based cellular appendages that are present throughout the hierarchy of the animal kingdom. These appendages are utilized for a wide array of functions such as motility in single celled organisms to coordinating complex cellular signaling pathways in more complex organisms. Though these appendages are well conserved, the exact function of cilia in many cell types remains unknown. Recently, cilia are tied to a myriad of developmental diseases and diseases of adult homeostasis collectively referred to as ciliopathies. Dysfunction in cilia results in a wide array of phenotypes ranging from retinal degeneration to polydactyly, cystic kidney disease, and …
Examination Of 4-Hydroxy Tamoxifen- And Bh3 Mimetic-Induced Cell Death Pathways In Glioblastoma And Malignant Peripheral Nerve Sheath Tumor Cells, Christopher Dillon Graham
Examination Of 4-Hydroxy Tamoxifen- And Bh3 Mimetic-Induced Cell Death Pathways In Glioblastoma And Malignant Peripheral Nerve Sheath Tumor Cells, Christopher Dillon Graham
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Glioblastoma (GBM) is the most common and aggressive human primary malignant brain tumor with a 5-year survival rate of less than 5%. GBM is highly invasive, rendering complete surgical resection impossible. Additionally, this tumor type is relatively insensitive to radiotherapy. Thus, effective chemotherapeutic options present the last line of defense for GBM patients. Unfortunately, nearly 50% of all GBM tumors are resistant to the current chemotherapeutic standard, temozolomide (TMZ). TMZ is a DNA alkylating agent that promotes apoptosis via DNA damage. Resistance to TMZ-induced cell death is attributed to expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) resultant from …