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Articles 1 - 30 of 72
Full-Text Articles in Medicine and Health Sciences
Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano
Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano
All ETDs from UAB
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Two major factors in both familial and sporadic PD are mitochondrial dysfunction and insufficient autophagy. My thesis research focuses on the interplay between these activities in PD. To investigate the common and differential effects of PD-inducing neurotoxins on mitochondrial bioenergetics and their relationships to cell survival, we used an in vitro culture system, differentiated dopaminergic SH-SY5Y neuroblastoma cells. We found that the neurotoxins rotenone, 1-methyl-4- phenylyridinium (MPP+) and 6-hydroxydopamine (6-OHDA), decreased mitochondrial respiration and induced cell death in these cells. The extent and characteristics of mitochondrial dysfunction in response to …
Rhodopsin As A Model For Gpcr Trafficking And Its Role In Outer Segment Formation, Joshua D. Sammons
Rhodopsin As A Model For Gpcr Trafficking And Its Role In Outer Segment Formation, Joshua D. Sammons
All ETDs from UAB
Rhodopsin is a prototypical G-protein coupled receptor whose biological function has been well worked out, yet little is known about the mechanism by which it is so efficiently transported to the rod outer segment (ROS) after synthesis. If rhodopsin is not efficiently transported to the ROS, rod cells will apoptose leading to cone cell apoptosis as well which results in the blinding disease retinitis pigmentosa. Work has begun to elucidate proteins responsible for transporting rhodopsin to the ROS using Xenopus laevis as a model since the photoreceptors of this amphibian are large and transgenic animals are relatively easy to prepare. …
Modulation Of Neocortical Gabaergic Interneurons By Voltage-Gated Ion Channels, Sidney B. Williams
Modulation Of Neocortical Gabaergic Interneurons By Voltage-Gated Ion Channels, Sidney B. Williams
All ETDs from UAB
GABAergic interneurons provide the main source of inhibition in the neocortex and are important in regulating neocortical network activity. In the presence of the K+ channel blocker 4-AP and the glutamate receptor blockers, CNQX and D-APV, large amplitude evoked and spontaneous depolarizing responses are observed in the neocortex. These large propagating responses are blocked by GABAA receptor antagonists indicating that these events are due to synchronized activity of GABAergic interneurons. Cortical GABAergic networks are comprised of several types of interneurons, each with its own protein expression pattern, receptor profile, firing properties, synaptic targets and role in network activity. Voltage-gated ion …
Osteomimmunology Of Bone Fracture Healing And Cell And Gene Therapy Approaches For Nonunion Bone Defects, Seth G. Levy
Osteomimmunology Of Bone Fracture Healing And Cell And Gene Therapy Approaches For Nonunion Bone Defects, Seth G. Levy
All ETDs from UAB
Despite the body's ability to repair bone fractures under normal circumstances, up to 10% of the 7.9 million fractures suffered in the United States each year do not achieve bony union. Bone fractures heal with overlapping phases of inflammation, cell proliferation, and bone remodeling. Osteogenesis and angiogenesis are known to work in concert to control many stages of this process, but when one is impaired it leads to failure of bone healing, referred to as a nonunion. Such nonunion fractures often result from critical-size defects that will not completely heal over the natural lifetime of the animal. Based on this …
Modulation Of The Immune Response To Aspergillus Fumigatus By Antibodies To Conserved Bacterial Polysaccharides, Emily Stefanov
Modulation Of The Immune Response To Aspergillus Fumigatus By Antibodies To Conserved Bacterial Polysaccharides, Emily Stefanov
All ETDs from UAB
The incidence of asthma, allergies and autoimmune diseases has increased dramatically in developed countries. The hygiene hypothesis postulates that excessively sanitary conditions lead to a lack of critical immune stimulation during early life, leading to inappropriate responses to self or harmless antigens later in life. Many bacteria and potential allergens share common polysaccharide epitopes. We investigated the ability of antibodies against these shared polysaccharides to dampen the immune response to the ubiquitous fungus and potent allergen, Aspergillus fumigatus. We found that antibodies against these polysaccharides, specifically of the IgM isotype, induced by neonatal bacterial immunization or passive antibody transfer, dampened …
Characterization Of Phosphatidylinositol 4,5-Bisphosphate Regulation Of The Electrogenic Na/Bicarbonate Cotransporter Nbce1, Ian Michael Thornell
Characterization Of Phosphatidylinositol 4,5-Bisphosphate Regulation Of The Electrogenic Na/Bicarbonate Cotransporter Nbce1, Ian Michael Thornell
All ETDs from UAB
The electrogenic Na/bicarbonate cotransporter (NBCe1) is an acid/base regulator that is also involved in coordinating epithelial ion transport. Splice variants of NBCe1 differ at their cytosolic amino- (N-) and/or carboxy- (C-) termini. These different cytosolic termini impart differential regulation for each variant. For example, the N-terminus of NBCe1-A is autostimulatory, whereas the N-terminus of NBCe1-B and -C is autoinhibitory. We examine the regulatory role of PIP2 for NBCe1 splice variants. In the first study of this dissertation, we characterize the effect of increasing PIP2 on the activity of NBCe1-A, -B, and -C expressed in Xenopus laevis oocytes. Injecting PIP2 stimulated …
Targeting Reactive Oxygen Species Production To Prevent Left Ventricle Remodeling In Volume Overload, Danielle Marie Yancey
Targeting Reactive Oxygen Species Production To Prevent Left Ventricle Remodeling In Volume Overload, Danielle Marie Yancey
All ETDs from UAB
Mechanisms of left ventricular dysfunction in cardiac volume overload (VO) are not well understood and currently, no medical therapy exists to treat this condition. Cardiac VO is marked by eccentric remodeling and contractile dysfunction ultimately resulting in cardiac failure. Oxidative stress is implicated in the pathophysiology of heart failure and recent evidence suggests mitochondrially- produced reactive oxygen species play a role in VO. To study VO, we used a rat model of aortocaval fistula (ACF). ACF results in early diastolic stress on the left ventricle (LV) and recapitulates the progressive nature of heart failure with contractile function being initially maintained …
Usp16 And Histone H2a Deubiquitination In Mouse Embryonic Stem Cell Function, Wei Yang
Usp16 And Histone H2a Deubiquitination In Mouse Embryonic Stem Cell Function, Wei Yang
All ETDs from UAB
In eukaryotic cells, genomic DNA is packaged into a chromatin structure by association with histone and non-histone proteins. Posttranslational modifications of histones play important roles in the regulation of chromatin structure and function. Ubiquitination of histone H2A (ubH2A) represents a predominate modification, occurring on ~10% of total cellular H2A. While H2A ubiquitination is primarily conferred by Polycomb Repressive Complex 1 (PRC1), H2A deubiquitination has been attributed to multiple H2A deubiquitinases. Our laboratory previously reported the purification and functional characterization of a H2A-specific deubiquitinase, USP16 (initially named as Ubp-M) in human cells. However, whether USP16 represents a general and important regulator …
The Role Of Primary Cilia In Mammary Gland And Skeletal Development, Elizabeth Mitchell
The Role Of Primary Cilia In Mammary Gland And Skeletal Development, Elizabeth Mitchell
All ETDs from UAB
Primary cilia (PC) extend from the cell body into the microenvironment detecting chemical and mechanical signals, and are required for proper development. To evaluate loss of primary cilia in mammary gland development, we developed mouse models with deletion of PC in mammary epithelial compartments. No discernable alterations to mammary development were observed in MMTV-Cre- or K14-Cre; Ift88Del lines. PC were expressed at high levels on cells in mammosphere culture; however, PC were not required for mammosphere renewal. The inability to find a significant mammary developmental phenotype in our mouse models suggested primary cilia don't have a significant function in differentiated …
Sialic Acid: A Signal For Pneumococcal Egress From The Nasal Mucosa Into The Central Nervous System, Brandon L. Hatcher
Sialic Acid: A Signal For Pneumococcal Egress From The Nasal Mucosa Into The Central Nervous System, Brandon L. Hatcher
All ETDs from UAB
Streptococcus pneumoniae (pneumococcus) is one of the leading causes of bacterial meningitis world-wide. The classic paradigm in the establishment of bacterial meningitis is that in the absence of physical trauma, infection in the peripheral blood is needed to cause invasion of the central nervous system (CNS). Our previous studies have shown that pneumococci, a frequent colonizer of the nasopharynx, can cause bacterial meningitis through a nonhematogenous route by which bacteria appear to travel along the olfactory nerves, through the cribriform plate to the olfactory bulbs and into the rest of the CNS. However, with the frequency of nasopharyngeal colonization and …
Molecular And Functional Interaction Of Runx2 And Sp7 For Development Of The Osteoblast Phenotype, Harunur Rashid
Molecular And Functional Interaction Of Runx2 And Sp7 For Development Of The Osteoblast Phenotype, Harunur Rashid
All ETDs from UAB
Runx2 and Sp7 transcription factors are essential for skeletogenesis. Deletion of either gene in mice results in failure of bone tissue development. However, underlying mechanisms responsible for a surprisingly similar phenotype by two distinctly unrelated proteins remain unknown. Sp7 is a Runx2 downstream target gene and is not expressed in Runx2 null mice. Thus, the Runx2 null model represents a compound phenotype of loss of both proteins. In contrast, normal levels of Runx2 mRNA are noted in Sp7 null mice. The failure of Runx2 to promote bone formation in Sp7 null mice suggests that Sp7 is required for Runx2 function …
Francisella Tularensis Lvs Invasion Of Primary Murine Macrophages And Mtor Signaling, Michael Warren Edwards
Francisella Tularensis Lvs Invasion Of Primary Murine Macrophages And Mtor Signaling, Michael Warren Edwards
All ETDs from UAB
Francisella tularensis is an intracellular pathogen and the etiologic agent of tularemia. Because virulent strains cause morbidity and lethality in human, the attenuated live vaccine strain (LVS) has been used to study F. tularensis pathogenesis in murine models, since the disease in mice resembles human tularemia. Despite growing knowledge about host responses to Francisella infection, there is scarce information on the cell signaling events involved in Francisella host cell entry and in early immune re-sponses. Therefore, the purpose of this dissertation was to assess the involvement of the mammalian target of rapamycin (mTOR) in these processes. First, we evaluated the …
Modulating The Cxcl12/Cxcr4 Axis In The Pulmonary Vasculature By Adenoviral Vector-Mediated Delivery Of Soluble Cxcr4 (Scxcr4): A Prophylactic Approach To The Prevention Of Cancer Metastasis To The Lung, Anand Chandrasekaran Annan
Modulating The Cxcl12/Cxcr4 Axis In The Pulmonary Vasculature By Adenoviral Vector-Mediated Delivery Of Soluble Cxcr4 (Scxcr4): A Prophylactic Approach To The Prevention Of Cancer Metastasis To The Lung, Anand Chandrasekaran Annan
All ETDs from UAB
Cancer metastasis is a multi-step process, and different cancer cells metastasize to different organs. The process includes proliferation and angiogenesis of the primary tumor, detachment of the primary tumor and invasion of the tumor into the lymphatics and capillaries, with embolization of the tumor cells to distant organs. The tumor cells then undergo arrest followed by extravasation with establishment of the tumor microenvironment and proliferation/angiogenesis of tumor cells to develop metastatic clones. However, evidence of metastasis is almost always associated with a poor prognosis. Multiple treatment modalities are being evaluated for cancer metastasis targeting one or more of the aforementioned …
Assessing The Active Kinome Of Influenza Virus Infected A549 Cells, Colm Atkins
Assessing The Active Kinome Of Influenza Virus Infected A549 Cells, Colm Atkins
All ETDs from UAB
Influenza A Virus is a respiratory pathogen of the family Orthomyxoviridae and causes significant worldwide morbidity and mortality during seasonal epidemics and periodic pandemics. As with all viruses, influenza's limited coding capacity requires the use of host proteins and processes in its replication and release cycle. Phosphorylation, mediated by cellular kinases and phosphatases, represents a significant mechanism of post-translational modification of cellular products, and is responsible for regulating the activi-ty, lifespan and localization of many lipids and proteins in host-cells. Several cellular kinases have been associated with various steps of the Influenza lifecycle, including PKC-ßII (viral entry), PKR (host defense), …
Il-8 Is Necessary And Sufficient For X-Ray Radiation Enhanced Endothelial Adhesion., Stephen Kyle Babitz
Il-8 Is Necessary And Sufficient For X-Ray Radiation Enhanced Endothelial Adhesion., Stephen Kyle Babitz
All ETDs from UAB
Ionizing radiation (IR) is a potent inflammatory stimulus to the human body. In the vasculature, inflammation is a major contributing factor for atherosclerosis. In addition, radiation from several sources has been linked with increased risk for multiple cardiovascular complications. A key compnent of radiation associated inflammation is an increase in the adhesiveness of the endothelium which leads to a pathogenic accumulation of leukocytes in the vascular wall. This is one of the initial steps in vascular inflammation and leads to a number of adverse complications such as heart disease and stroke. The molecular mechanisms behind radiaton enhanced endothelial adhesion have …
Targeted Delivery Of Osteoinductive Peptides To Bone Graft Utilizing A Calcium Binding Domain To Enhance The Regenerative Potential, Jennifer Leigh Bain
Targeted Delivery Of Osteoinductive Peptides To Bone Graft Utilizing A Calcium Binding Domain To Enhance The Regenerative Potential, Jennifer Leigh Bain
All ETDs from UAB
Bone grafting procedures are common practice. Autogenous bone is considered optimal, however, complications associated with bone harvesting often lead clinicians to use off-the-shelf materials that have limited osteoinductivity. Alternatively, bioactive factors passively adsorbed onto various carriers are available. These materials, while effective, are expensive to produce, require supraphysiological doses, and have adverse side effects due to dissemination from the graft site. This dissertation aims to reintroduce osteoinductive factors to bone grafts to enhance regenerative capacity. Specifically, we utilized negatively-charged calcium-binding domains (polyglutamate) to anchor two osteoinductive peptides bone graft materials including an allograft, xenograft, alloplast, and bone cement. The peptides …
The Role Of The Developing Microbiome In Mucosal Defense Of The Neonatal Gut, Emily G. Blosser
The Role Of The Developing Microbiome In Mucosal Defense Of The Neonatal Gut, Emily G. Blosser
All ETDs from UAB
Neonatal late-onset sepsis is invasive infection occurring after the first 48 hours of life, and one of the leading causes of death among preterm infants in the United States and abroad. Infections with Gram-negative bacteria, such as Klebsiella pneumonia, occurring when bacteria translocate across premature gut epithelium into the bloodstream, can be particularly severe. Preterm infants in the neonatal intensive care unit undergo intense antibiotic regimens due to high risk of infection. Paradoxically, prolonged exposure of preterm infants to empiric antibiotic therapy early in the hospital stay is associated with increased risk of intestinal infection and death after adjustment for …
The Involvement Of The Ca2+-Independent Phospholipase A2ss In The Pathogenesis Of Type 1 Diabetes, Robert N. Bone
The Involvement Of The Ca2+-Independent Phospholipase A2ss In The Pathogenesis Of Type 1 Diabetes, Robert N. Bone
All ETDs from UAB
Type 1 diabetes is a metabolic disease characterized by hyperglycemia, an absolute deficiency in insulin, and the autoimmune-mediated destruction of pancreatic islet ß-cells. Since exogenous insulin does not effectively duplicate native ß-cell function and the need persists for life, strategies to prevent ß-cell death or promote ß-cell survival are expected to provide beneficial outcomes. Based on reports that Akt1 promotes ß-cell survival and proliferation, administration of viral vectors modified to effectively deliver constitutively active (CA)-Akt1 to ß-cells would be expected to be beneficial for the ß-cell. In freshly isolated islets, CA-Akt1 promoted ex vivo islet cell survival and ß-cell survival. …
Evaluation Of Tau As A Target For Alzheimer Disease And Other Conditions With Epileptiform Activity, Zhiyong Li
Evaluation Of Tau As A Target For Alzheimer Disease And Other Conditions With Epileptiform Activity, Zhiyong Li
All ETDs from UAB
Alzheimer disease (AD) is a devastating neurological condition that slowly destroys memory and thinking skills of the affected patients. No disease-modifying medications are available. While all the treatment against Aß (major component of one hallmark pathology of AD) failed in clinical trials, tau (major component of the other hallmark pathology of AD) is emerging as a better alternative. Germline knockout of tau does not cause overt abnormalities in young mice and prevents AD-like deficits in mouse models of AD. Germline knockout of tau also confers resistance to epileptiform activity in models of both AD and epilepsy. Therefore tau is proposed …
Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman
Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman
All ETDs from UAB
Calreticulin (CRT) is an ER chaperone and regulator of Ca2+ signaling which is increased following ER stress and in fibrotic and vascular fibroproliferative disorders. Previously, we demonstrated that ER CRT regulates type I collagen transcript, trafficking, secretion, and processing into the extracellular matrix (ECM). These studies investigated the role of CRT in regulating ECM production through control TGF-ß dependent signaling pathways. Our studies show that CRT -/- mouse embryonic fibroblasts (MEFs), rat lung fibroblasts, and human IPF lung fibroblasts with siRNA knockdown of CRT had impaired production of type I collagen and fibronectin when stimulated with TGF-ß. Similarly, knockdown of …
Expression Of The Influenza Protein M2 During Viral Infection Inhibits Cftr Activity, James David Londino
Expression Of The Influenza Protein M2 During Viral Infection Inhibits Cftr Activity, James David Londino
All ETDs from UAB
The purpose of these dissertation studies was to 1) determine whether influenza infection alters CFTR activity in polarized epithelium; 2) measure CFTR expression and activity in cells co-expressing influenza M2 protein; and 3) examine the role of M2 on the alteration of CFTR during viral infection. We determined that infection of polarized primary epithelial cells with influenza decreases CFTR expression and activity. In addition, individual cells infected with influenza had decreased CFTR conductance as measured by whole-cell patch clamp. We also found that the influenza ion channel, matrix protein 2 (M2), alone reduced CFTR expression and activity. M2 is expressed …
Contribution Of Kv4.2 To Neuronal Hyperexcitability In A Mouse Model Of Alzheimer's Disease, Alicia Marie Hall
Contribution Of Kv4.2 To Neuronal Hyperexcitability In A Mouse Model Of Alzheimer's Disease, Alicia Marie Hall
All ETDs from UAB
The incidence of Alzheimer's disease (AD) is increasing with the aging population and an astonishing 5.2 million Americans are affected by AD, the most common cause of dementia. Cognitive impairment worsens with declining hippocampal function. Neuronal hyperexcitability occurs early in the pathogenesis of AD and contributes to network imbalance and the seizure activity seen in AD patients. In other disorders with neuronal hyperexcitability, dysfunction in the dendrites often contributes, but dendritic excitability has not been studied in AD models. We used patch-clamp recordings to directly examine dendritic excitability in the CA1 region of the hippocampus. We found that dendrites, but …
Using Neuroimaging To Predict Treatment Response In Patients With Schizophrenia, Nathan Lyle Hutcheson
Using Neuroimaging To Predict Treatment Response In Patients With Schizophrenia, Nathan Lyle Hutcheson
All ETDs from UAB
Schizophrenia is a severe debilitating mental illness that affects approximately 1% of people worldwide. Compared to healthy controls (HC), patients with schizophrenia (SZ) have memory deficits, specifically prominent disruptions in their episodic memory. These memory disruptions are thought to be caused by altered structure and function of areas within the memory network, specifically the prefrontal and temporal lobe including the hippocampus. Recently, identifying biomarkers of treatment response by using neuroimaging has become a prominent area of interest in schizophrenia. Biomarkers in schizophrenia could help by allowing for more efficient treatment using current method and also the development of novel treatments. …
Mechanisms Of At101 [(-)-Gossypol] Induced Cytotoxicity In Malignant Peripheral Nerve Sheath Tumors, Niroop Kaza
Mechanisms Of At101 [(-)-Gossypol] Induced Cytotoxicity In Malignant Peripheral Nerve Sheath Tumors, Niroop Kaza
All ETDs from UAB
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived sarcomas and are the leading cause of mortality in patients with neurofibromatosis type 1 (NF1). Current treatment modalities have been largely ineffective resulting in a high rate of MPNST recurrence and poor five year patient survival. This necessitates the exploration of alternative chemotherapeutic options for MPNST patients. By evading apoptosis and utilizing protective mechanisms such as autophagy, cancer cells develop resistance to chemo- and radio-therapy. The overall goal of my thesis studies is to evaluate chemotherapeutic agents that can modulate both apoptosis and autophagy, thus target both cell death pathways …
Regulation Of Cks1 Protein Turnover In Cancer Cells, Vinayak Khattar
Regulation Of Cks1 Protein Turnover In Cancer Cells, Vinayak Khattar
All ETDs from UAB
Cks1 is a crucial cell cycle regulator which plays pleiotropic roles in cancer cell growth and is highly expressed at both the protein, and mRNA levels, in cancer cells. In contrast, normal cells exhibit barely detectable levels of this protein, even though they express substantial Cks1 mRNA. One reason for high Cks1 protein in cancers appears to be its stabilization in these cells. Cks1 is known to be ubiquitinated and degraded by the proteasome. Coordinated ubiquitination dependent proteasomal degradation of cell cycle proteins is a major mechanism that regulates their activity. Therefore aberrant accumulation of Cks1, frequently observed in cancer, …
Type I Interferons-Induced Follicular Translocation Of Lymphotoxin-Expressing Marginal Zone B Cells Initiates Lupus, Hao Li
All ETDs from UAB
Systemic lupus erythematosus (SLE) is characterized by elevation of type I interferon (IFN) signature genes and production of autoantibodies against apoptotic self-antigens. The complex nature of SLE, however, suggests that multiple immune dysregulations must integrate to initiate the disease. Here, we provided evidence that lupus can be initiated via type I IFNs-induced follicular translocation of membrane lymphotoxin (mLT)-expressing marginal zone (MZ) B cells in the spleen of lupus prone BXD2 mice. The mislocation of mLT+ MZ B cells induces two important pathogenic effects including deteriorations of marginal zone macrophages (MZMs) in the MZ, leading to defective clearance of apoptotic debris, …
Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker
Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker
All ETDs from UAB
Vitally important to HIV-1 vaccine and prevention studies is a well-characterized animal model that recapitulates the salient features of HIV infection in humans. SIVmac and SIVsmm infection of rhesus macaques share key virological and pathological parallels with HIV-1 infection of humans including target cell entry via CD4 and CCR5 (Edinger et al., 1997), progressive T cell loss (Swanstrom & Coffin, 2012), generalized immune activation and preferential loss of mucosal Th17 cells (Brenchley et al., 2008; Klatt & Brenchley, 2010), and a vigorous but ultimately ineffective adaptive immune response. Though commonly used as a vaccine challenge strain in the macaque model, …
Altered Dna Methylation Contributes To Temporal Lobe Epilepsy And Associated Memory Deficits, Robert Ryley Parrish
Altered Dna Methylation Contributes To Temporal Lobe Epilepsy And Associated Memory Deficits, Robert Ryley Parrish
All ETDs from UAB
Status epilepticus (SE) triggers molecular mechanisms that underlie the cellular and network changes that occur during the development of temporal lobe epilepsy (TLE). Additionally, gene expression alterations occur during epileptogenesis and in the epileptic brain that contribute to the persistence of the phenotype. However, the underlying epigenetic mechanisms responsible for aberrant gene expression that occur with epilepsy require further investigation. This dissertation investigates how DNA methylation in the hippocampus affects epilepsy and contributes to the memory impairments associated with the disorder. We found that DNA methylation was altered in a hippocampal subregion specific manner in the epileptic brain, displaying altered …
Translocation Of Shed Syndecan-1 To The Nucleus: A Novel Mechanism Of Tumor-Host Crosstalk, Mark Stewart
Translocation Of Shed Syndecan-1 To The Nucleus: A Novel Mechanism Of Tumor-Host Crosstalk, Mark Stewart
All ETDs from UAB
Multiple myeloma is a hematological malignancy of plasma cells that disseminates throughout the body. Crosstalk between myeloma and host cells is critical to the establishment of a microenvironment conducive to tumor growth and progression. An important mediator of this crosstalk is syndecan-1, a heparan sulfate proteoglycan. Syndecan-1 is proteolytically shed from the surface of myeloma cells and is abundant in the bone marrow microenvironment and serum of myeloma patients. Shed syndecan-1 facilitates tumor-host crosstalk within the microenvironment to drive tumor growth, angiogenesis, and metastasis. We now report for the first time that shed syndecan-1 can be taken up by a …
Targeting Tau-Mediated Nmdar Hypofunction Reverses Deficits In A Mouse Model Of Frontotemporal Dementia, Brian Andrew Warmus
Targeting Tau-Mediated Nmdar Hypofunction Reverses Deficits In A Mouse Model Of Frontotemporal Dementia, Brian Andrew Warmus
All ETDs from UAB
Frontotemporal dementia (FTD) is a rapidly progressive and lethal disease, with no disease-modifying treatments. It is known that tau mutations cause FTD, but the underlying neurobiology is undefined. We sought to identify how tau affects the neurobiology in order to find potential treatment targets. Here, we address this question using a new mouse model expressing human tau with an FTD-associated mutation. We studied behavior, physiology, biochemistry, and neuropathology in several cohorts of mice at different ages. These mutant tau mice had abnormal repetitive behavior characteristic of FTD and synaptic deficits selectively in regions associated with FTD (ventral striatum and insula). …