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Full-Text Articles in Medicine and Health Sciences
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
All ETDs from UAB
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 …
Targeting The Tumor-Promoting Microenvironment With Inhibitors Of Pro-Hgf Activation, Benjamin Yaw Owusu
Targeting The Tumor-Promoting Microenvironment With Inhibitors Of Pro-Hgf Activation, Benjamin Yaw Owusu
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The tumor microenvironment plays a key role in tumor progression and therapeutic resistance. Hepatocyte growth factor (HGF), commonly expressed by cancer-associated fibroblasts, mediates signaling via its receptor, MET, and promotes survival, proliferation, migration and invasion of cancer cells. In addition, HGF dependence has emerged as a hallmark of therapeutic resistance. HGF is secreted as an inactive precursor, pro-HGF, which requires proteolytic cleavage and processing to form the mature, active HGF. This is the rate-limiting step in the HGF/MET signaling pathway and it is achieved by one of the serine proteases, matriptase, hepsin and HGF activator (HGFA). At Southern Research, we …
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 …
Microglia Orchestrate The Inflammatory Response To Alpha-Synuclein In Parkinson Disease Models, Aaron Thome
Microglia Orchestrate The Inflammatory Response To Alpha-Synuclein In Parkinson Disease Models, Aaron Thome
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Parkinson disease (PD) is the most common neurodegenerative movement disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and widespread aggregates of the protein alpha-synuclein (α-syn). Increasing evidence points to inflammation as a chief mediator of PD with many of the inflammatory manifestations of human PD cases recapitulated in animal models of PD. We began by examining the inflammatory potential of α-syn fibrils, a newly characterized α-syn conformation that is neurotoxic and prion-like in its endogenous α-syn recruitment and cellular transmission. Our studies provide evidence that the α-syn fibrils evoke a pro-inflammatory response …
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, …
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 …
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 …
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 …
Novel Biomarkers For Parkinson Disease, Kyle Bradley Fraser
Novel Biomarkers For Parkinson Disease, Kyle Bradley Fraser
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Parkinson disease (PD) is the most common neurodegenerative movement disorder for which no treatments exist capable of slowing progression of the disease. One obstacle slowing the development of novel therapies is the lack of molecular biomarkers for PD prognosis, tracking of disease progression, and assessing efficacious target engagement of compounds that do reach clinical trials. Missense mutations in LRRK2 account for between 1-5% of late onset PD and lead to increases in LRRK2 kinase activity and LRRK2 autophosphorylation. This thesis characterizes the secretion of LRRK2 into extracellularly secreted microvesicles called exosomes. We find that kinase-active LRRK2 is secreted within exosomes …
Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover
Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover
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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, …
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
All ETDs from UAB
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 …
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 …
Development Of A Split Luciferase Complementation Assay To Investigate Growth Hormone Receptor/ Prolactin Receptor Homo-/ Hetero-Association, Ying Liu
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Growth hormone receptor (GHR) and prolactin receptor (PRLR) are transmembrane glycoproteins cytokine receptors that are structurally homologous. Each can pre-homodimerize and ligand binding of each activates JAK2-STAT signaling pathways by inducing conformational change within the receptor homodimer. Human GHR can be activated by growth hormone (GH) while human PRLR can be activated by both GH and prolactin (PRL). We devised a split luciferase complementation assay, in which one receptor is fused to the N-terminal fragment of luciferase and the other receptor is fused to the C-terminal fragment of luciferase. When the two receptors approximate, luciferase activity (complementation) results. Using this …
Neurodevelopmental Alterations In A Rodent Model Of Temperamental Differences, Chelsea Mccoy Mccoy
Neurodevelopmental Alterations In A Rodent Model Of Temperamental Differences, Chelsea Mccoy Mccoy
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Understanding biological mechanisms that shape brain development and susceptibility to emotional dysfunction is crucial for generating improved treatments for depression and anxiety disorders. To study neurodevelopmental factors that influence emotionality, we use model rats that were bred for distinct behavioral responses to novelty. Rats bred for low novelty response (LRs) exhibit a high anxiety-/depressive-like phenotype compared to high novelty responder rats (HRs), which vigorously explore novelty and exhibit high impulsivity, aggression, and risk-taking. Transcriptome profiling revealed multiple gene expression differences in the early postnatal hippocampus and amygdala and in the adult amygdala of HR/LR rats. Through gene ontology analysis, we …
Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell
Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell
All ETDs from UAB
It is known that the vacuolar ATPase has a number of functions related to tumor growth and progression such as involvement in drug resistance, pH regulation, autophagy, and lysosomal acid protease activation, as well as invasion and metastasis. Here we specifically describe the role of ATP6v1c1 in murine and human models of breast cancer. ATP6v1c1 is the dominant isoform of the coordinating subunit (ATP6v1c) involved in the assembly of the vacuolar ATPase complex which plays a key role in cancer growth and progression. We also describe how ATP6v1c1 knockdown impairs tumor nutrient signaling through mTORC1 and tumor cell proliferation, by …
Cell-Specific Pgc-1Α-Dependent Transcription: Implications For Cognitive And Motor Dysfunction, Laura Mcmeekin
Cell-Specific Pgc-1Α-Dependent Transcription: Implications For Cognitive And Motor Dysfunction, Laura Mcmeekin
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Expression and/or function of transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is reduced in a variety of both neurodegenerative and psychiatric disorders. However, it is difficult to determine the significance of decreased PGC-1α expression and/or function in disease without knowing 1) the localization of these changes, 2) what the normal function of PGC-1α is in that specific cell-type, and 3) how its role in one neuronal population is different from its role in another. PGC-1α is highly expressed in GABAergic interneurons, and although it plays a significant role in interneuron function, several reports suggest that it also plays …
Transcriptional Regulation Of Interleukin 10 In Cd4+ T Cells, Carson Edward Moseley
Transcriptional Regulation Of Interleukin 10 In Cd4+ T Cells, Carson Edward Moseley
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Autoimmune and autoinflammatory diseases are a collection of disorders that are mediated by reaction of the adaptive immune system against self or commensal antigens. Altered transcription of genes involved in T cell activation and function is a key mediator of predisposition to numerous autoimmune disorders, including Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). However, we have an inadequate understanding of how the transcriptional circuits controlling these genes are dysregulated in disease. Interleukin-10 (IL-10) is cytokine with potent anti-inflammatory activity that is critical for restraining immune-mediated pathology to self-tissues. Notably, patients with nullifying mutations in IL10 develop a severe IBD …
Neonatal Microbial Exposure And Its Effects On The B Cell Repertoire And Development Of Respiratory Allergies, Preeyam Patel
Neonatal Microbial Exposure And Its Effects On The B Cell Repertoire And Development Of Respiratory Allergies, Preeyam Patel
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The incidence of asthma has increased dramatically among children living in developed countries, and the hygiene hypothesis suggests that this is the result of decreased neonatal exposure to microbes. Microbes and allergens can bear similar antibody-reactive epitopes, and exposure to microbes bearing these epitopes during early life can permanently alter the frequency and clonality of the antigen-specific B cell repertoire. The objective of this dissertation was to determine if B cells stimulated by microbes during early life could suppress the development of respiratory allergies during adult life. Both Streptococcus pneumoniae (pneumococcus) and house dust mite (HDM) express antibody-reactive phosphorylcholine (PC) …
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 …
Genome-Wide Transcription And Dna Methylation Profiling In An App Mouse Model Of Alzheimer’S Disease, Mikael C. Guzman Karlsson
Genome-Wide Transcription And Dna Methylation Profiling In An App Mouse Model Of Alzheimer’S Disease, Mikael C. Guzman Karlsson
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The ability to encode information for long-term behavioral adaptation relies on experience-dependent alterations in neuronal plasticity. Neuronal plasticity encompasses the cellular and molecular changes that modulate synaptic communication between neurons as well as intrinsic electrophysiological properties within neurons. Epigenetic mechanisms, including DNA cytosine methylation and histone post-translational modifications, are powerful regulators of neuronal gene expression, allowing for dynamic, bidirectional regulation of transcriptional signatures necessary for neuronal plasticity. Emerging evidence using candidate-gene and microarray-based approaches suggest that the deficits in neuronal plasticity and cognitive impairment observed in Alzheimer’s disease (AD) is attributable, in part, to aberrant cytosine methylation and transcription of …
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 …
Genetic Enhancer Screen With Transition Zone Mutant Nphp-4 Reveals Novel Interactions With Mutation Affecting Intraflagellar Transport And Endocytic Pathways, Scott Henke
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Cilia are hair-like microtubule based protrusions from the cell membrane. The Transition Zone (TZ) is a vital sub-domain of cilia and is located at the base of the cilium above the basal body at the entry point into the cilium. While multiple proteins associated with Nephronophthisis (NPHP), Bardet-Biedl Syndrome (BBS) and Meckel Gruber Syndrome (MKS) have been found to specifically localize to this region, little is known about their function. However, because non-ciliary proteins ectopically localize to the cilium in TZ mutants, it is hypothesized that TZ proteins control the trafficking of signaling proteins into and out of the cilium. …
What's Up, Dut? Help, Help I'M Being Derepressed; The Great Derepression Of Sapis Or How I Learned To Stop Worrying And Love Mobilization, Rosanne Lorin Lee Hill
What's Up, Dut? Help, Help I'M Being Derepressed; The Great Derepression Of Sapis Or How I Learned To Stop Worrying And Love Mobilization, Rosanne Lorin Lee Hill
All ETDs from UAB
Staphylococcus aureus is known to cause disease in both human and animal populations. Many of the virulence factors important for S. aureus pathogenesis are found on mobile genetic elements known as S. aureus pathogenicity islands (SaPIs). SaPIs can transduce into surrounding cells, giving those cells the ability to produce virulence factors. Derepression allows SaPIs to be excised from S. aureus genome to initiate mobilization. Derepressors have been identified for multiple SaPIs, but it remains unknown if the same SaPI can be derepressed by multiple derepressors. It has been shown that SaPIbov1 can be derepressed by the type 1 dUTPase from …
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 …
Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough
Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough
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Cerebral blood flow is regulated by vasoactive molecules released by astroglial cell processes that ensheath the entire cerebrovasculature. This regulation of blood flow in response to neuronal activity is a process known as functional hyperemia. Astrocytes, along with their associated neurons and microvessels, are organized into a functional system called the gliovascular unit (GVU). The astroglial component of the GVU is integral in both regulation of blood flow and maintenance of the blood-brain barrier (BBB). In disease, this system can be disrupted. We found that glioma cells displace astrocytic processes, called endfeet, and prevent their communication with associated vessels, leading …
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 …
Leukemia Stem Cell Markers And Inv(16) In Acute Myeloid Leukemia, Jason Legrand
Leukemia Stem Cell Markers And Inv(16) In Acute Myeloid Leukemia, Jason Legrand
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Although greater than 85% of inv(16) acute myeloid leukemia patients are able to achieve first complete remission after anthracycline- and cytarabine-based therapy, only about 60% of patients survive the disease long-term due to relapsed disease or treatment-related mortality. Multiple studies have shown that acute myeloid leukemia is composed of heterogeneous populations of leukemic clones that can exhibit a wide degree of genetic, epigenetic, and functional diversity, accounting for different outcomes in response to therapy. Genomic analysis of leukemic clones in paired diagnostic and relapse samples of acute myeloid leukemia has shown that all relapses stem from surviving leukemic or ancestral …
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 …
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 …