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Cell Biology

2010

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Articles 1 - 30 of 31

Full-Text Articles in Molecular Biology

Dynamic Remodeling Of The Stressed Heart: Role Of Protein Degradation Pathways, Deborah Vela Dec 2010

Dynamic Remodeling Of The Stressed Heart: Role Of Protein Degradation Pathways, Deborah Vela

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The heart is a remarkable organ. In order to maintain its function, it remodels in response to a variety of environmental stresses, including pressure overload, volume overload, mechanical or pharmacological unloading and hormonal or metabolic disturbances. All these responses are linked to the inherent capacity of the heart to rebuild itself. Particularly, cardiac pressure overload activates signaling pathways of both protein synthesis and degradation. While much is known about regulators of protein synthesis, little is known about regulators of protein degradation in hypertrophy. The ubiquitin-proteasome system (UPS) selectively degrades unused and abnormal intracellular proteins. I speculated that the UPS may ...


Novel Constitutively Active Point Mutations In The Nh2 Domain Of Cxcr2 Capture The Receptor In Different Activation States, Giljun Park Dec 2010

Novel Constitutively Active Point Mutations In The Nh2 Domain Of Cxcr2 Capture The Receptor In Different Activation States, Giljun Park

Doctoral Dissertations

Chemokines are structurally and functionally related 8-10 kDa proteins defined by four conserved cysteine residues. They consist of a superfamily of proinflammatory mediators that promote the recruitment of various kinds of leukocytes and other cell types through binding to their respective chemokine receptor, a member of the GPCR family. Abnormal control of this system results in various diseases including tumorigenesis and cancer metastasis. Deregulation can occur when constitutively active mutant (CAM) chemokine receptors are locked in the “on” position. This can lead to cellular transformation/tumorigenesis. A viral CAM receptor, ORF74, that can cause tumors in humans, also has homology ...


Production, Purification And Crystallization Of Membrane Integrated Multimeric Bax, Adelbert Mark Villoso Dec 2010

Production, Purification And Crystallization Of Membrane Integrated Multimeric Bax, Adelbert Mark Villoso

UNLV Theses, Dissertations, Professional Papers, and Capstones

Apoptosis, or programmed cell death, is a vital process intimately involved in the embryonic development and homeostatic maintenance of all multicellular organisms. The committing step to apoptosis is regulated by a key protein, Bax, and its ability to integrate and form a pore structure at the outer mitochondrial membrane.


Unfortunately, the molecular details of apoptosis remain largely unclear due to the lack of structural data of integral membrane (IM) Bax. Experimental limitations of membrane protein production have slowed the pursuit of an IM-Bax structure simply because standard protocols for producing recombinant IM-Bax are inefficient in producing adequate quantities of IM-Bax ...


Virulence Of An Emerging Respiratory Pathogen, Genus Pandoraea, In Vivo And Its Interactions With Lung Epithelial Cells, Gillian Herbert, Anne Costello, Lydia Fabunmi, Kirsten Schaffer, Kevin Kavanagh, Emma M. Caraher, Máire Callaghan, Siobhan Mcclean Nov 2010

Virulence Of An Emerging Respiratory Pathogen, Genus Pandoraea, In Vivo And Its Interactions With Lung Epithelial Cells, Gillian Herbert, Anne Costello, Lydia Fabunmi, Kirsten Schaffer, Kevin Kavanagh, Emma M. Caraher, Máire Callaghan, Siobhan Mcclean

Articles

Pandoraea species have emerged as opportunistic pathogens among cystic fibrosis (CF) and non-CF patients. Pandoraea pulmonicola is the predominant Pandoraea species among Irish CF patients. The objective of this study was to investigate the pathogenicity and potential mechanisms of virulence of Irish P. pulmonicola isolates and strains from other Pandoraea species. Three patients from whom the P. pulmonicola isolates were isolated have since died. The in vivo virulence of these and other Pandoraea strains was examined by determining the ability to kill Galleria mellonella larvae. The P. pulmonicola strains generally were the most virulent of the species tested, with three ...


Molecular Mechanism Of Agc Kinases In Human Malignant, Shaokun Shu Oct 2010

Molecular Mechanism Of Agc Kinases In Human Malignant, Shaokun Shu

Graduate Theses and Dissertations

The maintenance of normal cell function and tissue homeostasis is dependent on the precise regulation of multiple signaling pathways that control cellular decisions to either proliferate, differentiate, arrest cell growth, or initiate programmed cell death (apoptosis). Cancer arises when clones of mutated cells escape this balance and proliferate inappropriately without compensatory apoptosis. Deregulated cell growth occurs as a result of perturbed signal transduction that modulates or alters cellular behavior or function to keep the critical balance between the rate of cell-cycle progression (cell division) and cell growth (cell mass) on one hand, and programmed cell death (apoptosis, autophagy) on the ...


Hippocampal C-Jun-N-Terminal Kinases Serve As Negative Regulators Of Associative Learning, Tessi Sherrin, Thomas Blank, Cathrin Hippel, Martin Rayner, Roger J. Davis, Cedomir Todorovic Oct 2010

Hippocampal C-Jun-N-Terminal Kinases Serve As Negative Regulators Of Associative Learning, Tessi Sherrin, Thomas Blank, Cathrin Hippel, Martin Rayner, Roger J. Davis, Cedomir Todorovic

Davis Lab Publications

In the adult mouse, signaling through c-Jun N-terminal kinases (JNKs) links exposure to acute stress to various physiological responses. Inflammatory cytokines, brain injury and ischemic insult, or exposure to psychological acute stressors induce activation of hippocampal JNKs. Here we report that exposure to acute stress caused activation of JNKs in the hippocampal CA1 and CA3 subfields, and impaired contextual fear conditioning. Conversely, intrahippocampal injection of JNKs inhibitors sp600125 (30 mum) or D-JNKI1 (8 mum) reduced activity of hippocampal JNKs and rescued stress-induced deficits in contextual fear. In addition, intrahippocampal administration of anisomycin (100 mug/mul), a potent JNKs activator, mimicked ...


Requirement Of Jip1-Mediated C-Jun N-Terminal Kinase Activation For Obesity-Induced Insulin Resistance, Caroline Morel, Claire L. Standen, Dae Young Jung, Susan Gray, Helena Ong, Richard A. Flavell, Jason K. Kim, Roger J. Davis Oct 2010

Requirement Of Jip1-Mediated C-Jun N-Terminal Kinase Activation For Obesity-Induced Insulin Resistance, Caroline Morel, Claire L. Standen, Dae Young Jung, Susan Gray, Helena Ong, Richard A. Flavell, Jason K. Kim, Roger J. Davis

Davis Lab Publications

The c-Jun NH(2)-terminal kinase (JNK) interacting protein 1 (JIP1) has been proposed to act as a scaffold protein that mediates JNK activation. However, recent studies have implicated JIP1 in multiple biochemical processes. Physiological roles of JIP1 that are related to the JNK scaffold function of JIP1 are therefore unclear. To test the role of JIP1 in JNK activation, we created mice with a germ line point mutation in the Jip1 gene (Thr(103) replaced with Ala) that selectively blocks JIP1-mediated JNK activation. These mutant mice exhibit a severe defect in JNK activation caused by feeding of a high-fat ...


The Human In 3d: Advanced Morphometric Analysis Of High-Resolution Anatomically Accurate Computed Models, Summer J. Decker Oct 2010

The Human In 3d: Advanced Morphometric Analysis Of High-Resolution Anatomically Accurate Computed Models, Summer J. Decker

Graduate Theses and Dissertations

Computed virtual models of anatomical structures are proving to be of increasing value in clinical medicine, education and research. With a variety of fields focused on craniofacial and pelvic anatomy there is a need for accurate anatomical models. Recent technological advancements in computer and medical imaging technologies have provided the tools necessary to develop three-dimensional (3D) functional models of human anatomy for use in medicine (surgical planning and education), forensics and engineering (computer-aided design (CAD) and finite element analysis).

Traditionally caliper methodologies are used in the quantitative analysis of human anatomy. In order for experts in anatomy and morphometrics to ...


Characterization Of Metastasis-Associated Cell Surface Glycoproteins In Prostate Cancer, Lifang Yang Oct 2010

Characterization Of Metastasis-Associated Cell Surface Glycoproteins In Prostate Cancer, Lifang Yang

Theses and Dissertations in Biomedical Sciences

Prostate cancer (PCa) is a major health problem in males in the United States. Its lethality is mostly attributed to the primary tumor metastasizing to distant sites that are highly resistant to conventional therapies. Serum Prostate Specific Antigen (PSA) is the only protein biomarker used in clinic for prediction of prostate cancer recurrence following local therapies. Nonetheless, PSA lacks the ability to predict the behavior of an individual tumor in an individual patient. Therefore, development of reliable biomarkers for detection of metastatic potential in primary tumors, as well as discovery of new therapeutic targets, is in a great need for ...


The Biogeochemistry Of Submerged Coastal Karst Features In West Central Florida, Keith Michael Garman Sep 2010

The Biogeochemistry Of Submerged Coastal Karst Features In West Central Florida, Keith Michael Garman

Graduate Theses and Dissertations

West Central Florida is a complex karst environment with numerous sinkholes, springs, and submerged cave systems. Many of these karst features are anchialine, located within the subterranean estuary where freshwater and saltwater mix. Water quality data and/or fauna data were obtained from twenty-one karst features and their associated cave systems. The anchialine karst environment of the study area has a wide range of habitats with measured salinities ranging from freshwater at <0.2 ppt to sulfidic, hypersaline water at 38.5 ppt and measured pH readings ranging from 6.39 in water impacted by sulfur oxidizing bacteria to 10.3 in an isolated room of a cave. Stygobitic crustaceans were identified in conduits extending beneath the Gulf of Mexico supporting the hypotheses that freshwater crustaceans could survive higher sea levels in freshwater conduits beneath saltwater. The fauna associated with the anchialine cave systems included Sabellidae and Polychaeta worms, hydroids, cnidarians and hydrobiid snails. Jewfish Sink, like other anaerobic marine basins that were submarine springs, has four zones: oxic zone, transition zone, upper anoxic zone and anoxic bottom water. The upper zones have seasonal water quality variations from winter cooling and sinking of surface water and changes in the microbial communities. Activity of sulfate reducing bacteria is carbon limited in the anoxic zones, where sulfate reduction is the major metabolic process, and primary production is phosphate limited in the oxic zones. Organic input from the Gulf of Mexico drives the bacterial anaerobic ecosystem, resulting in a “sulfide pump”, in which sulfide percolates upward removing oxygen from the overlying sediment.


Role And Regulation Of Epha2 In Pancreatic Cancer, Pavel A. Levin Aug 2010

Role And Regulation Of Epha2 In Pancreatic Cancer, Pavel A. Levin

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cancer cause of death in the US. Gemcitabine is the first-line therapy for this disease, but unfortunately it shows only very modest benefit. The focus of the current study was to investigate the role and regulation of EphA2, a receptor tyrosine kinase expressed in PDAC, to further understand this disease and identify new therapeutic targets.

The role of EphA2 was determined in PDAC by siRNA mediated silencing. In combination with gemcitabine, silencing of EphA2 caused a dramatic increase in apoptosis even in highly resistant cells in vitro. Furthermore, EphA2 silencing was found ...


The P38 Mapk Pathway Is Essential For Skeletogenesis And Bone Homeostasis In Mice, Matthew B. Greenblatt, Jae-Hyuck Shim, Weiguo Zou, Despina Sitara, Michelle Schweitzer, Dorothy Hu, Sutada Lotinun, Yasuyo Sano, Roland Baron, Jin Mo Park, Simon Arthur, Min Xie, Michael D. Schneider, Bo Zhai, Steven Gygi, Roger J. Davis, Laurie H. Glimcher Jul 2010

The P38 Mapk Pathway Is Essential For Skeletogenesis And Bone Homeostasis In Mice, Matthew B. Greenblatt, Jae-Hyuck Shim, Weiguo Zou, Despina Sitara, Michelle Schweitzer, Dorothy Hu, Sutada Lotinun, Yasuyo Sano, Roland Baron, Jin Mo Park, Simon Arthur, Min Xie, Michael D. Schneider, Bo Zhai, Steven Gygi, Roger J. Davis, Laurie H. Glimcher

Davis Lab Publications

Nearly every extracellular ligand that has been found to play a role in regulating bone biology acts, at least in part, through MAPK pathways. Nevertheless, much remains to be learned about the contribution of MAPKs to osteoblast biology in vivo. Here we report that the p38 MAPK pathway is required for normal skeletogenesis in mice, as mice with deletion of any of the MAPK pathway member-encoding genes MAPK kinase 3 (Mkk3), Mkk6, p38a, or p38b displayed profoundly reduced bone mass secondary to defective osteoblast differentiation. Among the MAPK kinase kinase (MAP3K) family, we identified TGF-beta-activated kinase 1 (TAK1; also known ...


Distinct Roles Of C-Jun N-Terminal Kinase Isoforms In Neurite Initiation And Elongation During Axonal Regeneration, Monia Barnat, Herve Enslen, Friedrich Propst, Roger J. Davis, Sylvia Soares, Fatiha Nothias Jun 2010

Distinct Roles Of C-Jun N-Terminal Kinase Isoforms In Neurite Initiation And Elongation During Axonal Regeneration, Monia Barnat, Herve Enslen, Friedrich Propst, Roger J. Davis, Sylvia Soares, Fatiha Nothias

Davis Lab Publications

c-Jun N-terminal kinases (JNKs) (comprising JNK1-3 isoforms) are members of the MAPK (mitogen-activated protein kinase) family, activated in response to various stimuli including growth factors and inflammatory cytokines. Their activation is facilitated by scaffold proteins, notably JNK-interacting protein-1 (JIP1). Originally considered to be mediators of neuronal degeneration in response to stress and injury, recent studies support a role of JNKs in early stages of neurite outgrowth, including adult axonal regeneration. However, the function of individual JNK isoforms, and their potential effector molecules, remained unknown. Here, we analyzed the role of JNK signaling during axonal regeneration from adult mouse dorsal root ...


Mechanisms Of The Downregulation Of Prolactin Receptor And Their Role In Cell Proliferation, Bentley J. Varghese May 2010

Mechanisms Of The Downregulation Of Prolactin Receptor And Their Role In Cell Proliferation, Bentley J. Varghese

Publicly Accessible Penn Dissertations

Cells react to diverse stimuli by expressing specific receptors that recognize these stimuli and initiate specific signaling pathways that enable a cell to change with the environment. Downregulation of these signaling receptors represents the most direct method for limiting the magnitude and duration of downstream signal transduction. For cell surface transmembrane receptors, ligand-stimulated endocytosis is a major mechanism by which the ability of a cell to react to a ligand is restricted. In order to investigate the downregulation of the prolactin receptor (PRLr), we investigated the mechanism and key determinants in the endocytosis and downregulation of PRLr. In Chapter 2 ...


Determination Of The Myogenic Potential Of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells, Rory Coleman May 2010

Determination Of The Myogenic Potential Of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells, Rory Coleman

Honors Scholar Theses

Human embryonic stem cells (hESCs) have the potential to

differentiate to all adult somatic cells. This property makes hESCs a very promising area of research for the treatment of disorders in which specific cell populations need to be restored. Despite this potential, research that focuses on producing mesodermally derived cell populations from hESCs is decidedly limited, notwithstanding the prevalence of disorders involving mesodermal tissues for which treatment options are limited. Skeletal muscle myoblasts are derivatives of mesodermal cells and are characterized by the expression of the MyoD gene. These cells are difficult to obtain from hESCs in a reproducible and ...


Characterization Of The Putative Xyloglucan Glycosyltransferase Gt14 In Arabidopsis Thaliana, Najam R. Syed May 2010

Characterization Of The Putative Xyloglucan Glycosyltransferase Gt14 In Arabidopsis Thaliana, Najam R. Syed

Honors Scholar Theses

Plant cell walls largely consist of matrix polysaccharides that are linked to cellulose microfibrils. Xyloglucan, the primary hemicellulose of the cell wall matrix, consists of a repeating glucose tetramer structure with xylose residues attached to the first three units ('XXXG'). In Arabidopsis thaliana, the core XXXG structure is further modified by enzymatic addition of galactose and fucose residues to the xylose side chains to produce XLXG, XXLG, XLLG and XLFG structures. GT14 is a putative glycosyltransferase in the GT47 gene family. Initial predictions of GT14's hydrophobic regions, based on its translated amino acid sequence, are almost identical to its ...


Alkylphenol Contamination In Homarus Americanus, Jennifer Renee Urban May 2010

Alkylphenol Contamination In Homarus Americanus, Jennifer Renee Urban

Honors Scholar Theses

Alkylphenols are pollutants that are present in marine sediments and fishes. In earlier work it has been discovered that alkylphenols are present in the Homarus americanus, or the American lobster. Research suggests that alkylphenols could behave as endocrine disruptors as they have been found to affect juvenile hormone activity. It has been hypothesized that lobsters may be able to rid themselves of alkylphenol contamination through secreting these compounds into the environment or sequestering them in their tissues. In this study, I address the question of how lobsters may rid themselves of alkylphenols by analyzing hemolymph, muscle, gill, and shell samples ...


Functional Analysis Of Chromodomain Helicase Dna Binding Protein 2(Chd2) Mediated Genomic Stability, Sangeetha Rajagopalan May 2010

Functional Analysis Of Chromodomain Helicase Dna Binding Protein 2(Chd2) Mediated Genomic Stability, Sangeetha Rajagopalan

Doctoral Dissertations

Histone modifying enzymes and chromatin remodeling complexes play an important regulatory role in chromatin dynamics that dictate the interaction of regulatory factors involved in processes such as DNA replication, recombination, repair and transcription, with DNA template. The CHD (Chromodomain Helicase DNA Binding Protein) family of proteins is known to be involved in the regulation of gene expression, recombination and chromatin remodeling via their chromatin specific interactions and activities. Phenotypic analysis of the Chd2 mutant mouse model developed by our laboratory indicates that the Chd2 protein plays a critical role in tumor suppression as the heterozygous mutant mice develop spontaneous lymphomas ...


Analysis Of Apoptosis Of Memory T Cells And Dendritic Cells During The Early Stages Of Viral Infection Or Exposure To Toll-Like Receptor Agonists, Kapil Bahl, Anette Hubner, Roger J. Davis, Raymond M. Welsh May 2010

Analysis Of Apoptosis Of Memory T Cells And Dendritic Cells During The Early Stages Of Viral Infection Or Exposure To Toll-Like Receptor Agonists, Kapil Bahl, Anette Hubner, Roger J. Davis, Raymond M. Welsh

Davis Lab Publications

Profound type I interferon (IFN-I)-dependent attrition of memory CD8 and CD4 T cells occurs early during many infections. It is dramatic at 2 to 4 days following lymphocytic choriomeningitis virus (LCMV) infection of mice and can be elicited by the IFN-inducing Toll receptor agonist poly(I:C). We show that this attrition occurs in many organs, indicating that it is due to T cell loss rather than redistribution. This loss correlated with elevated intracellular staining of T cells ex vivo for activated caspases but with only low levels of ex vivo staining with annexin V, probably due to the ...


Microtubule Stabilization By Bone Morphogenetic Protein Receptor-Mediated Scaffolding Of C-Jun N-Terminal Kinase Promotes Dendrite Formation, Monika Podkowa, Xin Zhao, Chi-Wing Chow, Eleanor T. Coffey, Roger J. Davis, Liliana Attisano May 2010

Microtubule Stabilization By Bone Morphogenetic Protein Receptor-Mediated Scaffolding Of C-Jun N-Terminal Kinase Promotes Dendrite Formation, Monika Podkowa, Xin Zhao, Chi-Wing Chow, Eleanor T. Coffey, Roger J. Davis, Liliana Attisano

Davis Lab Publications

Neuronal outgrowth occurs via coordinated remodeling of the cytoskeleton involving both actin and microtubules. Microtubule stabilization drives the extending neurite, yet little is known of the molecular mechanisms whereby extracellular cues regulate microtubule dynamics. Bone morphogenetic proteins (BMPs) play an important role in neuronal differentiation and morphogenesis, and BMP7 in particular induces the formation of dendrites. Here, we show that BMP7 induces stabilization of microtubules in both a MAP2-dependent neuronal cell culture model and in dendrites of primary cortical neurons. BMP7 rapidly activates c-Jun N-terminal kinases (JNKs), known regulators of microtubule dynamics, and we show that JNKs associate with the ...


Genetic And Biochemical Studies Of Plasmid Pir52-1 In Lactobacillus Helveticus, Cody Alexander Tramp May 2010

Genetic And Biochemical Studies Of Plasmid Pir52-1 In Lactobacillus Helveticus, Cody Alexander Tramp

Undergraduate Honors Capstone Projects

Lactobacillus helveticus is a species of lactic acid bacteria. These bacteria, which produce lactic acid as a major product of carbohydrate metabolism, are used industrially to produce cheese and other fermented dairy products (Ebringer et al., 2008). Many species of lactic acid bacteria also possess probiotic characteristics and when ingested potentially confer increased immune function, regulate gut microbiota, and improve digestion in the host (Reid, 2008). Genetic studies of these probiotic effects and other characteristics of L. helveticus and related species have been hindered by the lack of stably replicating plasmid vectors. Plasmid vectors for several Lactobacillus species have been ...


Md-2-Mediated Ionic Interactions Between Lipid A And Tlr4 Are Essential For Receptor Activation, Jianmin Meng, Egil Lien, Douglas T. Golenbock Mar 2010

Md-2-Mediated Ionic Interactions Between Lipid A And Tlr4 Are Essential For Receptor Activation, Jianmin Meng, Egil Lien, Douglas T. Golenbock

Infectious Diseases and Immunology Publications

Lipopolysaccharide (LPS) activates innate immune responses through TLR4.MD-2. LPS binds to the MD-2 hydrophobic pocket and bridges the dimerization of two TLR4.MD-2 complexes to activate intracellular signaling. However, exactly how lipid A, the endotoxic moiety of LPS, activates myeloid lineage cells remains unknown. Lipid IV(A), a tetra-acylated lipid A precursor, has been used widely as a model for lipid A activation. For unknown reasons, lipid IV(A) activates proinflammatory responses in rodent cells but inhibits the activity of LPS in human cells. Using stable TLR4-expressing cell lines and purified monomeric MD-2, as well as MD-2-deficient bone marrow-derived ...


Reverse Genetic And Cell Biological Approaches To The Study Of Developmental Functions Of Class Xi Myosin In Arabidopsis Thaliana, Eunsook Park Mar 2010

Reverse Genetic And Cell Biological Approaches To The Study Of Developmental Functions Of Class Xi Myosin In Arabidopsis Thaliana, Eunsook Park

Doctoral Dissertations

Myosin proteins function as molecular motors that drive the ATP-dependent movement of cellular components along actin filaments. Vascular plants encode two different types of myosin, referred to as class VIII and class XI. Although class XI myosins have been suggested to function in organelle movement and cytoplasmic streaming, little is known about their cellular function in detail.

The Arabidopsis genome encodes 13 class XI myosin genes. The reasons for the relatively large number of myosin XI isoforms present within a single plant species are unknown. To investigate the function of these gene products in the cell, we determined the spatial ...


C-Jun Nh2-Terminal Kinase Is Required For Lineage-Specific Differentiation But Not Stem Cell Self-Renewal, Ping Xu, Roger J. Davis Mar 2010

C-Jun Nh2-Terminal Kinase Is Required For Lineage-Specific Differentiation But Not Stem Cell Self-Renewal, Ping Xu, Roger J. Davis

Davis Lab Publications

The c-Jun NH(2)-terminal kinase (JNK) is implicated in proliferation. Mice with a deficiency of either the Jnk1 or the Jnk2 genes are viable, but a compound deficiency of both Jnk1 and Jnk2 causes early embryonic lethality. Studies using conditional gene ablation and chemical genetic approaches demonstrate that the combined loss of JNK1 and JNK2 protein kinase function results in rapid senescence. To test whether this role of JNK was required for stem cell proliferation, we isolated embryonic stem (ES) cells from wild-type and JNK-deficient mice. We found that Jnk1(-/-) Jnk2(-/-) ES cells underwent self-renewal, but these cells proliferated ...


Role Of The Hypothalamic-Pituitary-Thyroid Axis In Metabolic Regulation By Jnk1, Guadalupe Sabio, Julie Cavanagh-Kyros, Tamera Barrett, Dae Young Jung, Hwi Jin Ko, Helena Ong, Caroline Morel, Alfonso Mora, Judith Reilly, Jason K. Kim, Roger J. Davis Feb 2010

Role Of The Hypothalamic-Pituitary-Thyroid Axis In Metabolic Regulation By Jnk1, Guadalupe Sabio, Julie Cavanagh-Kyros, Tamera Barrett, Dae Young Jung, Hwi Jin Ko, Helena Ong, Caroline Morel, Alfonso Mora, Judith Reilly, Jason K. Kim, Roger J. Davis

Davis Lab Publications

The cJun N-terminal kinase 1 (JNK1) is implicated in diet-induced obesity. Indeed, germline ablation of the murine Jnk1 gene prevents diet-induced obesity. Here we demonstrate that selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. The failure to increase body mass is mediated, in part, by increased energy expenditure that is associated with activation of the hypothalamic-pituitary-thyroid axis. Disruption of thyroid hormone function prevents the effects of nervous system JNK1 deficiency on body mass. These data demonstrate that the hypothalamic-pituitary-thyroid axis represents an important target of metabolic signaling by JNK1.


The Role Of Ledgf/P75 In Transcriptional Regulation, Jeffrey Ryan Kugelman Jan 2010

The Role Of Ledgf/P75 In Transcriptional Regulation, Jeffrey Ryan Kugelman

Open Access Theses & Dissertations

The Lens Epithelial Derived Growth Factor p75 (LEDGF/p75) is a chromatin bound protein whose cellular function is not yet clearly known. A role in transcriptional regulation had been previously proposed based on its interaction with the basal transcriptional machinery and on its effects on the expression of genes involved in the cellular response to environmental stresses. To further elucidate the function of LEDGF/p75, we conducted a global and unbiased evaluation of the role of this protein in gene expression. To that aim, we performed a microarray analysis of cellular gene expression in cells that are severely depleted of ...


Phosphorylation Of The Glycine Transporter 1, Javier Vargas Medrano Jan 2010

Phosphorylation Of The Glycine Transporter 1, Javier Vargas Medrano

Open Access Theses & Dissertations

The extracellular levels of the neurotransmitter glycine in the brain are tightly regulated by the high-affinity glycine transporter 1 (GlyT1) and the clearance of glycine depends on its rate of transport and the levels of cell surface GlyT1. Over the past years, it has been shown that PKC activation diminishes the activity and promoted phosphorylation of several neurotransmitter transporters including the dopamine, serotonin and norepinephrine transporters however, its role is unknown for the glycine transporter. To get insights into the role of PKC activation on GlyT1 regulation, we used three N-terminus GlyT1 isoforms stably expressed in porcine aortic endothelial (PAE ...


Role Of Muscle C-Jun Nh2-Terminal Kinase 1 In Obesity-Induced Insulin Resistance, Guadalupe Sabio, Norman J. Kennedy, Julie Cavanagh-Kyros, Dae Young Jung, Hwi Jin Ko, Helena Ong, Tamera Barrett, Jason K. Kim, Roger J. Davis Jan 2010

Role Of Muscle C-Jun Nh2-Terminal Kinase 1 In Obesity-Induced Insulin Resistance, Guadalupe Sabio, Norman J. Kennedy, Julie Cavanagh-Kyros, Dae Young Jung, Hwi Jin Ko, Helena Ong, Tamera Barrett, Jason K. Kim, Roger J. Davis

Davis Lab Publications

Obesity caused by feeding of a high-fat diet (HFD) is associated with an increased activation of c-Jun NH(2)-terminal kinase 1 (JNK1). Activated JNK1 is implicated in the mechanism of obesity-induced insulin resistance and the development of metabolic syndrome and type 2 diabetes. Significantly, Jnk1(-)(/)(-) mice are protected against HFD-induced obesity and insulin resistance. Here we show that an ablation of the Jnk1 gene in skeletal muscle does not influence HFD-induced obesity. However, muscle-specific JNK1-deficient (M(KO)) mice exhibit improved insulin sensitivity compared with control wild-type (M(WT)) mice. Thus, insulin-stimulated AKT activation is suppressed in muscle, liver, and ...


Functional Cooperation Of The Proapoptotic Bcl2 Family Proteins Bmf And Bim In Vivo, Anette Hubner, Julie Cavanagh-Kyros, Mercedes Rincon, Richard Flavell, Roger J. Davis Jan 2010

Functional Cooperation Of The Proapoptotic Bcl2 Family Proteins Bmf And Bim In Vivo, Anette Hubner, Julie Cavanagh-Kyros, Mercedes Rincon, Richard Flavell, Roger J. Davis

Davis Lab Publications

Bcl2-modifying factor (Bmf) is a member of the BH3-only group of proapoptotic proteins. To test the role of Bmf in vivo, we constructed mice with a series of mutated Bmf alleles that disrupt Bmf expression, prevent Bmf phosphorylation by the c-Jun NH(2)-terminal kinase (JNK) on Ser(74), or mimic Bmf phosphorylation on Ser(74). We report that the loss of Bmf causes defects in uterovaginal development, including an imperforate vagina and hydrometrocolpos. We also show that the phosphorylation of Bmf on Ser(74) can contribute to a moderate increase in levels of Bmf activity. Studies of compound mutants ...


The Pax-5 Gene Is Alternatively Spliced In Trout B Cells, Raaj Mahendra Talauliker Jan 2010

The Pax-5 Gene Is Alternatively Spliced In Trout B Cells, Raaj Mahendra Talauliker

Dissertations, Theses, and Masters Projects

No abstract provided.