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Articles 61 - 80 of 80
Full-Text Articles in Life Sciences
Notch1 Functions As A Tumor Suppressor In A Model Of K-Ras–Induced Pancreatic Ductal Adenocarcinoma, Linda Hanlon, Jacqueline L Avila, Renée M Demarest, Scott Troutman, Megan Allen, Francesca Ratti, Anil K Rustgi, Ben Z Stanger, Fred Radtke, Volkan Adsay, Fenella Long, Anthony J Capobianco, Joseph L Kissil
Notch1 Functions As A Tumor Suppressor In A Model Of K-Ras–Induced Pancreatic Ductal Adenocarcinoma, Linda Hanlon, Jacqueline L Avila, Renée M Demarest, Scott Troutman, Megan Allen, Francesca Ratti, Anil K Rustgi, Ben Z Stanger, Fred Radtke, Volkan Adsay, Fenella Long, Anthony J Capobianco, Joseph L Kissil
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
K-ras is the most commonly mutated oncogene in pancreatic cancer and its activation in murine models is sufficient to recapitulate the spectrum of lesions seen in human pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that Notch receptor signaling becomes reactivated in a subset of PDACs, leading to the hypothesis that Notch1 functions as an oncogene in this setting. To determine whether Notch1 is required for K-ras-induced tumorigenesis, we used a mouse model in which an oncogenic allele of K-ras is activated and Notch1 is deleted simultaneously in the pancreas. Unexpectedly, the loss of Notch1 in this model resulted in increased …
Cannabinoid-Mediated Inhibition Of Recurrent Excitatory Circuitry In The Dentate Gyrus In A Mouse Model Of Temporal Lobe Epilepsy, Muthu D. Bhaskaran, Bret N. Smith
Cannabinoid-Mediated Inhibition Of Recurrent Excitatory Circuitry In The Dentate Gyrus In A Mouse Model Of Temporal Lobe Epilepsy, Muthu D. Bhaskaran, Bret N. Smith
Physiology Faculty Publications
Temporal lobe epilepsy (TLE) is a neurological condition associated with neuron loss, axon sprouting, and hippocampal sclerosis, which results in modified synaptic circuitry. Cannabinoids appear to be anti-convulsive in patients and animal models of TLE, but the mechanisms of this effect are not known. A pilocarpine-induced status epilepticus mouse model of TLE was used to study the effect of cannabinoid agonists on recurrent excitatory circuits of the dentate gyrus using electrophysiological recordings in hippocampal slices isolated from control mice and mice with TLE. Cannabinoid agonists WIN 55,212-2, anandamide (AEA), or 2-arachydonoylglycerol (2-AG) reduced the frequency of spontaneous and tetrodotoxin-resistant excitatory …
Ligand-Induced Conformations Of Extracellular Loop 2 Of At1r, Hamiyet Unal
Ligand-Induced Conformations Of Extracellular Loop 2 Of At1r, Hamiyet Unal
ETD Archive
Angiotensin II type 1 receptor (AT1R) is a G-protein coupled receptor (GPCR) and an important regulator of blood pressure. It is a target for drug development, because abnormalities in its function are linked to hypertension, cardiac hypertrophy and heart failure. AT1R is composed of seven transmembrane helices connected by three extracellular loops and three intracellular loops. The extracellular loop 2 (ECL2) of AT1R directly interacts with the ligands. This loop is targeted by autoantibodies that activate AT1R in several pathologies such as preeclampsia, malignant hypertension and vascular allograft rejection. Therefore, we proposed that the conformation of ECL2 in AT1R is …
Effects Of Simvastatin And 6-Hydroxydopamine Lesion On Histaminergic H1 Receptor Binding In Rat Brains, C H. Hu, C Deng, Xu-Feng Huang, J Chen, Q Wang
Effects Of Simvastatin And 6-Hydroxydopamine Lesion On Histaminergic H1 Receptor Binding In Rat Brains, C H. Hu, C Deng, Xu-Feng Huang, J Chen, Q Wang
Faculty of Health and Behavioural Sciences - Papers (Archive)
No abstract provided.
Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli
Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
BACKGROUND: The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS), which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of …
Excitatory And Inhibitory Neurotransmission Is Chronically Altered Following Perinatal Nmda Receptor Blockade, Kelly A. Newell, Xu-Feng Huang, Chao Deng, Teresa M. Du Bois, Mei Han
Excitatory And Inhibitory Neurotransmission Is Chronically Altered Following Perinatal Nmda Receptor Blockade, Kelly A. Newell, Xu-Feng Huang, Chao Deng, Teresa M. Du Bois, Mei Han
Faculty of Health and Behavioural Sciences - Papers (Archive)
N-methyl-d-aspartate (NMDA) receptor blockade in rodents induces behavioural and neurochemical changes reminiscent of schizophrenia symptoms and pathology. To examine how NMDA receptor blockade affects glutamatergic and GABAergic pathways when administered during early brain development, [3H]MK-801 and [3H]muscimol binding to NMDA and GABAA receptors was examined at four time-points following injections of phencyclidine (PCP) or saline on postnatal days (PN)7, 9 and 11. [3H]MK-801 binding was significantly increased in PCP-treated rats in the thalamus from PN18 to PN96, in the prefrontal and anterior cingulate cortices at PN32, and in the hippocampus at PN96. In a similar manner, [3H]muscimol binding was increased …
Characterizing The Polycation Receptor Of Paramecium, Eric D. Robinette, Heather G. Kuruvilla
Characterizing The Polycation Receptor Of Paramecium, Eric D. Robinette, Heather G. Kuruvilla
Science and Mathematics Faculty Presentations
Unicellular eukaryotes are complex systems, performing all the tasks needed for survival within the context of a single cell. Protozoans, such as Tetrahymena and Paramecium, use chemosensory systems to detect food and to avoid predation.
Both Tetrahymena and Paramecium have been used as models for studying chemorepellents. Lysozyme, ATP, and GTP have been found to have chemorepellent activity in both ciliates. In Tetrahymena, several PACAP isoforms have been shown to bind to the same receptor as lysozyme, indicating that this receptor may be a more general “polycation receptor” (Keedy et al., 2003). The polycation receptor in Tetrahymena appears to be …
Autocrine Effects Of Catecholamines On Macrophage Release Of Interleukin-6 (Il-6), Shaunta D. Poe
Autocrine Effects Of Catecholamines On Macrophage Release Of Interleukin-6 (Il-6), Shaunta D. Poe
Theses and Dissertations
Effects of norepinephrine (NE) on macrophage cytokine release are complex because the cells have both α2 and β2 adrenergic receptors, which mediate opposing actions. Furthermore, β2-adrenergic agonists are reported to have both stimulatory and inhibitory effects on interleukin-6 (IL-6). This study was designed to clarify the autocrine role of macrophage-derived NE on IL-6 production in activated peritoneal macrophages. Effects of NE on IL-6 production in the RAW264.7 macrophage cell-line also were investigated. Treatment of activated peritoneal macrophages with endotoxin, the α2-adrenergic antagonists yohimbine or RS79948 revealed that the α2-adrenergic receptor mediates a stimulatory autocrine action of catecholamines on IL-6 production. …
Novel Characteristics Of Murine Bone Marrow-Derived Macrophages And Human Macrophage-Like Cells, George Tharwat Georges
Novel Characteristics Of Murine Bone Marrow-Derived Macrophages And Human Macrophage-Like Cells, George Tharwat Georges
Theses and Dissertations
These studies provide evidence for novel properties of macrophages derived from bone marrow stem cells. In study 1, treatment of activated mouse bone marrow-derived macrophages (BMM) with either catecholamine synthesis inhibitors (α-methyl-para-tyrosine and fusaric acid) or the β2 adrenergic receptor antagonist ICI 118,551 demonstrated that BMM produce catecholamines. The catecholamines modulated macrophage cytokine production through autocrine actions on adrenergic receptors. In study II, undifferentiated human bone marrow cells were incubated in 30% mouse L929 fibroblast conditioned medium and generated adherent cells within three days. The cells were clearly identifiable as macrophages based on surface proteins and phagocytic activity but produced …
A Critical Role For Kalirin In Ngf Signaling Through Trka, Kausik Chakrabarti, Rong Lin, Noraisha I. Schiller, Yanping Wang, David Koubi, Ying-Xin Fan, Brian B. Rudkin, Gibbes R. Johnson, Martin R. Schiller
A Critical Role For Kalirin In Ngf Signaling Through Trka, Kausik Chakrabarti, Rong Lin, Noraisha I. Schiller, Yanping Wang, David Koubi, Ying-Xin Fan, Brian B. Rudkin, Gibbes R. Johnson, Martin R. Schiller
Life Sciences Faculty Research
Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low …
In Vivo Characterization Of The Integrin Beta(3) As A Receptor For Hantaan Virus Cellular Entry, Jin-Won Song, Ki-Joon Song, Luck-Ju Baek, Blaise Frost
In Vivo Characterization Of The Integrin Beta(3) As A Receptor For Hantaan Virus Cellular Entry, Jin-Won Song, Ki-Joon Song, Luck-Ju Baek, Blaise Frost
Chemistry Faculty Publications
No abstract provided.
Two Drosophila Suppressors Of Cytokine Signaling (Socs) Differentially Regulate Jak And Egfr Pathway Activities, Jason S. Rawlings, Gabriela Rennebeck, Susan M.W. Harrison, Rongwen Xi, Douglas A. Harrison
Two Drosophila Suppressors Of Cytokine Signaling (Socs) Differentially Regulate Jak And Egfr Pathway Activities, Jason S. Rawlings, Gabriela Rennebeck, Susan M.W. Harrison, Rongwen Xi, Douglas A. Harrison
Biology Faculty Publications
BACKGROUND: The Janus kinase (JAK) cascade is an essential and well-conserved pathway required to transduce signals for a variety of ligands in both vertebrates and invertebrates. While activation of the pathway is essential to many processes, mutations from mammals and Drosophila demonstrate that regulation is also critical. The SOCS (Suppressor Of Cytokine Signaling) proteins in mammals are regulators of the JAK pathway that participate in a negative feedback loop, as they are transcriptionally activated by JAK signaling. Examination of one Drosophila SOCS homologue, Socs36E, demonstrated that its expression is responsive to JAK pathway activity and it is capable of downregulating …
Loss-Of-Function Analysis Of Epha Receptors In Retinotectal Mapping, David Feldheim, Masaru Nakamoto, Miriam Osterfield, Nicholas Gale, Thomas Dechiara, Rajat Rohatgi, George Yancopoulos, John Flanagan
Loss-Of-Function Analysis Of Epha Receptors In Retinotectal Mapping, David Feldheim, Masaru Nakamoto, Miriam Osterfield, Nicholas Gale, Thomas Dechiara, Rajat Rohatgi, George Yancopoulos, John Flanagan
Biology Faculty Publications
EphA tyrosine kinases are thought to act as topographically specific receptors in the well-characterized projection map from the retina to the tectum. Here, we describe a loss-of-function analysis of EphA receptors in retinotectal mapping. Expressing patches of a cytoplasmically truncated EphA3 receptor in chick retina caused temporal axons to have reduced responsiveness to posterior tectal repellent activity in vitro and to shift more posteriorly within the map in vivo . A gene disruption of mouse EphA5, replacing the intracellular domain with beta-galactosidase, reduced in vitro responsiveness of temporal axons to posterior target membranes. It also caused map abnormalities in vivo …
Reactivity Profiles Of Ligands Of Mammalian Retinoic Acid Receptors: A Preliminary Corepa Analysis, Steven P. Bradbury, G. T. Ankley, O. G. Mekenyan, V. . Kamenska, P. K. Schmieder
Reactivity Profiles Of Ligands Of Mammalian Retinoic Acid Receptors: A Preliminary Corepa Analysis, Steven P. Bradbury, G. T. Ankley, O. G. Mekenyan, V. . Kamenska, P. K. Schmieder
Steven P. Bradbury
Retinoic acid and associated derivatives comprise a class of endogenous hormones that bind to and activate different families of retinoic acid receptors (RARs, RXRs), and control many aspects of vertebrate development. Identification of potential RAR and RXR ligands is of interest both from a pharmaceutical and toxicological perspective. The recently developed COREPA (COmmon REactivity PAttern) algorithm was used to establish reactivity profiles for a limited data set of retinoid receptor ligands in terms of activation of three RARs (a, b, g) and an RXR (a). Conformational analysis of a training set of retinoids and related analogues in terms of thermodynamic …
A Glu-496 To Ala Polymorphism Leads To Loss Of Function Of The Human P2x7 Receptor, Ben J. Gu, Weiyi Zhang, Rebecca A. Worthington, Ronald Sluyter, L Phuong Dao-Ung, Stephen Petrou, J A. Barden, James Wiley
A Glu-496 To Ala Polymorphism Leads To Loss Of Function Of The Human P2x7 Receptor, Ben J. Gu, Weiyi Zhang, Rebecca A. Worthington, Ronald Sluyter, L Phuong Dao-Ung, Stephen Petrou, J A. Barden, James Wiley
Faculty of Science - Papers (Archive)
P2X(7) receptor is a ligand-gated cation-selective channel that mediates ATP-induced apoptosis of cells of the immune system. We and others have shown that P2X(7) is nonfunctional both in lymphocytes and monocytes from some subjects. To study a possible genetic basis we sequenced DNA coding for the carboxyl-terminal tail of P2X(7). In 9 of 45 normal subjects a heterozygous nucleotide substitution (1513A-->C) was found, whereas 1 subject carried the homozygous substitution that codes for glutamic acid to alanine at amino acid position 496. Surface expression of P2X(7) on lymphocytes was not affected by this E496A polymorphism, demonstrated both by confocal …
Deconstructing The Interaction Of Glu-Plasminogen With Its Receptor A-Enolase, N M. Andronicos, M S. Baker, M Lackmann, M Ranson
Deconstructing The Interaction Of Glu-Plasminogen With Its Receptor A-Enolase, N M. Andronicos, M S. Baker, M Lackmann, M Ranson
Faculty of Science - Papers (Archive)
No abstract provided.
Cell Signaling Pathways Elicited By Asbestos, B T. Mossman, S Faux, Y Janssen, L A. Jimenez, Cynthia Timblin, Christine Zanella, Jonathan Goldberg, Eric Walsh, Aaron Barchowsky, Kevin Driscoll
Cell Signaling Pathways Elicited By Asbestos, B T. Mossman, S Faux, Y Janssen, L A. Jimenez, Cynthia Timblin, Christine Zanella, Jonathan Goldberg, Eric Walsh, Aaron Barchowsky, Kevin Driscoll
Dartmouth Scholarship
In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrins. Alternatively, signaling pathways may be stimulated by active oxygen species generated both during phagocytosis of minerals and by redox reactions on the mineral surface. At least two signaling cascades linked to activation of transcription factors, i.e., DNA-binding proteins involved in modulating gene expression and DNA replication, are stimulated after exposure of lung cells to …
Correlative Light And Electron Microscopy Of Platelet Adhesion And Fibrinogen Receptor Expression Using Colloidal-Gold Labeling, Steven L. Goodman, Ralph M. Albrecht
Correlative Light And Electron Microscopy Of Platelet Adhesion And Fibrinogen Receptor Expression Using Colloidal-Gold Labeling, Steven L. Goodman, Ralph M. Albrecht
Scanning Microscopy
Differences in the shape change responses of platelets to various polymers may determine the thrombotic potential of these materials. Substrate-dependent variation in the expression and motility of the platelet fibrinogen receptor may underlie these differences due to this ligand's essential role in platelet aggregation. In this study we examine platelet activation on polyetherurethaneureas (PEUUs) presently being evaulated for vascular prosthetic applications. These polymers are prepared as 50-100nm thin films suitable as substrates for consecutive light microscopy, high voltage electron microscopy (HVEM), and SEM. 18nm colloidal gold coupled to fibrinogen permits visualization of that receptor's motility in living cells by video-enhanced …
Purification Of Anthrax Toxin Protective Antigen Component And Characterization Of Its Binding Interaction With Bovine Kidney Cells, Daniel Dalton Martin
Purification Of Anthrax Toxin Protective Antigen Component And Characterization Of Its Binding Interaction With Bovine Kidney Cells, Daniel Dalton Martin
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
Protective antigen component of B. anthracis toxin was produced and purified to the >99% level. Toxin was purified from culture supernatant utilizing concentration and liquid chromatography techniques. Purity was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
The purified protective antigen retained biological and antigenic activity as evidenced respectively by lethality in Fischer 344 rats when injected in combination with lethal factor, and by positive results on the Ouchterlony double diffussion assay.
Radioiodinated protective antigen was used both in the in vivo and the in vitro experiments.
In vivo distribution of labelled protective antigen was determined in Fischer 344 rats. Assay …
Sective Deficits In The Sense Of Smell Caused By Chemical Modification Of Olfactory Epithelium, J Russell Mason, Larry Clark, Thomas Morton
Sective Deficits In The Sense Of Smell Caused By Chemical Modification Of Olfactory Epithelium, J Russell Mason, Larry Clark, Thomas Morton
Larry Clark
A chemically selective procedure for covalent modification of Schiff base-forming binding sites in proteins is demonstrated in vitro. In vivo studies show that the same procedure produces a selective anosmia ("odor blindness") when applied to the olfactory epithelia of experimental animals. Surgical experiments confirm that the sense of smell is specifically affected.