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Full-Text Articles in Medicine and Health Sciences
Tuba, A Novel Protein Containing Bin/Amphiphysin/Rvs And Dbl Homology Domains, Links Dynamin To Regulation Of The Actin Cytoskeleton, Marco Antonio Del Valle Salazar
Tuba, A Novel Protein Containing Bin/Amphiphysin/Rvs And Dbl Homology Domains, Links Dynamin To Regulation Of The Actin Cytoskeleton, Marco Antonio Del Valle Salazar
Yale Medicine Thesis Digital Library
Tuba is a novel scaffold protein that functions to bring together dynamin with components of the actin cytoskeleton. It is concentrated at synapses in brain and binds dynamin selectively through four N-terminal Src homology-3 (SH3) domains. Tuba binds a variety of actin regulatory proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, and Ena/VASP proteins, via a C-terminal SH3 domain. Direct binding partners include N-WASP and Ena/VASP proteins. Forced targeting of the C-terminal SH3 domain to the mitochondrial surface can promote accumulation of F-actin around mitochondria. A Dbl homology domain present in the middle of Tuba upstream of a Bin/amphiphysin/Rvs (BAR) …
Direct Evidence For A Membrane Deforming Motif In Endophilin: Implications Beyond Synaptic Vesicle Recycling, Khashayar Farsad
Direct Evidence For A Membrane Deforming Motif In Endophilin: Implications Beyond Synaptic Vesicle Recycling, Khashayar Farsad
Yale Medicine Thesis Digital Library
Effective neurotransmission is dependent on fast, reproduceable synaptic vesicle recycling. The synaptic vesicle recycling process is a complex event involving both protein-protein, as well as protein-lipid interactions. A central part of the retrieval process of synaptic vesicles lies in the ability of soluble proteins to deform the plasma membrane into a nascent bud which will eventually reform a fully competent synaptic vesicle upon fission. This process involves clathrin-coat proteins, which form a protein scaffold around the vesicle bud, as well as proteins which have more recently been thought to be involved in generating the high curvature membranes present at the …
Mutagenesis Induced By The Tumor Microenvironment: Implications Of Increased Dna Damage And Diminished Dna Repair, Jianling Yuan
Mutagenesis Induced By The Tumor Microenvironment: Implications Of Increased Dna Damage And Diminished Dna Repair, Jianling Yuan
Yale Medicine Thesis Digital Library
Tumors are characterized by microenvironmental heterogeneity, with regions of hypoxia, low pH, and nutrient deprivation. It has been proposed that such conditions may be an important factor contributing to cancer genetic instability. Using a chromosomally based lambda phage shuttle vector as a mutation reporter, we show that growth of cells in hypoxia and/or at low pH results in elevated mutation frequencies in two different reporter genes. To elucidate the mechanism of the tumor microenvironment-induced genetic instability, we first measured the production of DNA damage upon hypoxia and re-oxygenation in culture. We found that under such conditions, the intracellular level of …
Icam-1 Transmembrane Signaling: Involvement Of Taxreb107 In Icam-1-Mediated Signal Transduction, Brian Lee
Icam-1 Transmembrane Signaling: Involvement Of Taxreb107 In Icam-1-Mediated Signal Transduction, Brian Lee
Yale Medicine Thesis Digital Library
The role of membrane ICAM-1 in intercellular adhesion, through interaction with the leukocyte beta2 integrin receptors LFA-1 and Mac-1, is well established. However, until recently, ICAM-1 was widely regarded as being simply an "anchor" molecule, promoting, for example, firm adhesion of lymphocytes to vascular endothelial cells. The demonstration that ICAM-1 is connected to the actin-based cytoskeleton through interactions with subcortical actin-binding proteins, such as alpha-actinin, enhanced this concept. However, ICAM-1 has been increasingly shown to have signaling properties of its own. Engagement of ICAM-1 extracellularly, either through its natural counter-receptors, LFA-1/Mac-1, or through antibody mediated clustering, can produce numerous changes …
Nudel, An Unusual Mosaic Protease Involved In Defining The Embryonic Dorsal-Ventral Axis Of Drosophila Melanogaster, Charles Chansik Hong
Nudel, An Unusual Mosaic Protease Involved In Defining The Embryonic Dorsal-Ventral Axis Of Drosophila Melanogaster, Charles Chansik Hong
Yale Medicine Thesis Digital Library
Dorsal-ventral polarity of the Drosophila embryo is determined by positional information that originates outside of the embryo. This information, which is created during oogenesis by the somatic follicle cells swrounding the oocyte, is utilized following fertilization to trigger a spatially regulated serine protease cascade in the extraembryonic perivitelline space. This protease cascade, which appears to be activated only on the presumptive ventral side of the embryo, generates the ligand for the Toll transmembrane protein that polarizes the embryo by inducing ventral development.This thesis presents evidence that nudel, a gene maternally required in somatic tissue for the formation of Toll's ligand, …
Modulation Of The Rat Potassium Channel Kv1.5, Daniel Benjamin Saal
Modulation Of The Rat Potassium Channel Kv1.5, Daniel Benjamin Saal
Yale Medicine Thesis Digital Library
1. Kv1.5 is a delayed rectifier-type potassium channel. We have examined the localization of the channel protein using a polyclonal antibody against Kv1.5. This channel is expressed in numerous regions of the brain, primarily in glial cells. Its expression is particularly intense in the endfoot processes which abut the microvasculature of the brain. It is also expressed in the cell bodies and cellular processes in the pituitary.2. Immunoprecipitation of the Kv1.5 protein, from HEK 293 cells which were transformed with the Kv1.5 gene, revealed that the channel is phosphorylated and that treatment of cells with dibutyryl cyclic AMP (dibcAMP) or …
The Cloning And Characterization Of Toad-64: A Gene Expressed Transiently During Neuronal Differentiation In The Mammalian Nervous System, Jane Elizabeth Minturn
The Cloning And Characterization Of Toad-64: A Gene Expressed Transiently During Neuronal Differentiation In The Mammalian Nervous System, Jane Elizabeth Minturn
Yale Medicine Thesis Digital Library
During the development of the mammalian central nervous system, a pool of morphologically homogeneous, mitotically active progenitor cells in the neural tube gives rise to the enormously diverse population of postmitotic cells that assume the properties of neurons or glia. Postmitotic neurons elaborate processes that are involved in the migration of neurons to their adult positions as well as the elaboration of axonal and dendritic arbors that will ultimately form specific synaptic contacts. The generation of postmitotic neurons from precursor cells is a central differentiative event in development, but molecular markers of this event are few.Using 2D gel electrophoresis, proteins …
Expression And Characterization Of Two Alternatively Spliced Isoforms Of Rat Type I Receptor For Inositol 1,4,5-Trisphosphate, Doris Da May Lin
Expression And Characterization Of Two Alternatively Spliced Isoforms Of Rat Type I Receptor For Inositol 1,4,5-Trisphosphate, Doris Da May Lin
Yale Medicine Thesis Digital Library
The transmembrane receptor for IP3 is a tetrameric calcium channel located in the endoplasmic reticulum. In many cell types the receptor mediates such complex signals as calcium waves and oscillations. There are multiple receptor isoforms, derived by alternative splicing as well as different genes. The functional significance of these many receptor isoforms has not been determined. To this end, I have generated cell lines that express homotetrameric receptors.Stable lines of the human embryonic kidney (HEK293) cells were established by transfection with cDNAs encoding for two splice variants of the rat type I receptor. The two variants differ in the presence …
The Spleen Focus-Forming Virus Envelope Glycoprotein, Gp55, And The Block In The Erythropoietin-Induced Differentiation Of Friend Murine Erythroleukemia Cells, Thomas Samuel Lin
The Spleen Focus-Forming Virus Envelope Glycoprotein, Gp55, And The Block In The Erythropoietin-Induced Differentiation Of Friend Murine Erythroleukemia Cells, Thomas Samuel Lin
Yale Medicine Thesis Digital Library
Unlike normal committed erythroid progenitor cells, which require erythropoietin (EPO) for both proliferation and terminal differentiation, Friend murine erythroleukemia (MEL) cells are EPO-independent and do not differentiate in response to the cytokine. Dimethylsulfoxide (DMSO) induces differentiation and restores responsiveness to EPO. DMSO-treated Friend cells responded to EPO with both increased proliferation and further hemoglobin synthesis. The effects of DMSO upon the expression of EPO receptor (EPOR) mRNA and cell surface receptor were examined. Clone DMSO/R1, an MEL subline resistant to the differentiation-inducing and EPO-sensitizing effects of DMSO, expressed a higher level of EPOR mRNA than parental Friend cells, and DMSO …
The Identification And Characterization Of Protein Tyrosine Phosphatases Expressed In The Developing Rat Brain, Mustafa Sahin
The Identification And Characterization Of Protein Tyrosine Phosphatases Expressed In The Developing Rat Brain, Mustafa Sahin
Yale Medicine Thesis Digital Library
Previous studies of the developing nervous system have shown that cell-cell and cell-matrix interactions are involved in a variety of processes such as the proliferation, migration and differentiation of neurons. While many cell surface molecules have been identified, the signal transduction mechanisms through which they alter cellular responses are poorly understood. Recent studies have described a new and large family of enzymes, protein tyrosine phosphatases (PTPases), that may play a key role in transduction of cell surface events. Opposing the actions of protein tyrosine kinases (PTKs), PTPases may determine the state of tyrosine phosphorylation of a protein and regulate its …
Expression And Function Of Zebra: The Epstein-Barr Viral Replication Activator, Naomi Taylor
Expression And Function Of Zebra: The Epstein-Barr Viral Replication Activator, Naomi Taylor
Yale Medicine Thesis Digital Library
Epstein-Barr virus (EBV) encodes a protein, ZEBRA, which enables the virus to switch from a latent to a lytic life cycle. ZEBRA expression was studied in lymphoid cells harboring either standard virus or a mixture of standard and defective viruses. ZEBRA protein could not be detected in cells latently infected with standard EBV but was constitutively expressed in cells containing both defective and standard EBV genomes. Experiments indicated that regulation of transcription of the ZEBRA gene (BZLF1) is a pivotal event in the control of EBV replication. ZEBRA specific BZLF1 transcripts were spontaneously expressed in cells harboring defective virus but …
The Regulation Of The Transferrin Receptor By Inducers Of Cellular Differentiation And By Antisense Phosphorothioate Oligodeoxynucleotides, Peter Tai-Ching Ho
The Regulation Of The Transferrin Receptor By Inducers Of Cellular Differentiation And By Antisense Phosphorothioate Oligodeoxynucleotides, Peter Tai-Ching Ho
Yale Medicine Thesis Digital Library
Modulation of surface transferrin receptor (TfR) activity has been associated with leukemia cell differentiation and proliferation. To examine the mechanisms involved in regulating this event, surface receptor protein and mRNA levels were measured in HL-60 promyelocytic leukemia cells induced to differentiate along the myelocytic and monocytic pathways. Surface TfR down-regulation which occurs during granulocytic differentiation by dimethylsulfoxide, retinoic acid, or aclacinomycin A appears to be kinetically compatible with reduced biosynthesis resulting from reductions in the level of steady-state mRNA. In contrast, biosynthetic modulation does not appear to mediate the intial surface receptor down-regulation seen during 12-O-tetradecanoylphorbol-13-acetate-induced macrophagic differentiation. However, a …
Gene Expression During The Latent And Replicative States Of The Epstein-Barr Virus, Ronald John Weigel
Gene Expression During The Latent And Replicative States Of The Epstein-Barr Virus, Ronald John Weigel
Yale Medicine Thesis Digital Library
Gene expression of the Epstein-Barr virus (EBV) was examined during the latent and lytic viral cycles. During latency the virus expresses two small RNAs (EBERs) and the EB nuclear antigen (EBNA). A gene encoding one peptide of the EBNA complex was mapped using S1 nuclease analysis. EBNA peptide is encoded by a 2028 base exon contained within the EBV Bam HI K fragment; the 3' end of this exon occurs 30 bp after the polyadenylation signal AATAAA and the 5' end occurs within a splice acceptor site. The latent state was disrupted experimentally by treatment with phorbol ester or superinfection …
Chemiosmotic Properties Of Isolated Secretory Granules From Parotid Glands Of Normal And Isoproterenol Treated Rats, Peter Raymond Arvan
Chemiosmotic Properties Of Isolated Secretory Granules From Parotid Glands Of Normal And Isoproterenol Treated Rats, Peter Raymond Arvan
Yale Medicine Thesis Digital Library
Secretory granule fractions were prepared isoosmotically from the parotid glands of normal rats and from rats that had received repeated injections of isoproterenol. These granules, purified extensively, are stable after isolation, making it possible to study biophysical parameters which may relate to their role in intracellular transport and secretion.Normal parotid granules have an internal pH of (TURN)6.8 and a low ionic permeability with respect to internal buffering capacity. By contrast, granules from the treated rats have an internal pH ranging from (TURN)7.7 in (0.3 M) sucrose media to (TURN)7.1 in (100 mM) KCl media; suggesting a large ionic permeability with …
Studies Of Plasma Membrane Domain-Specific Molecules In Isolated And Cultured Rat Hepatocytes, Pamela Leslie Zeitlin
Studies Of Plasma Membrane Domain-Specific Molecules In Isolated And Cultured Rat Hepatocytes, Pamela Leslie Zeitlin
Yale Medicine Thesis Digital Library
Single rat hepatocytes, prepared by collagenase perfusion of liver, lost the three morphologically and functionally distinct plasma membrane domains that exist in situ (sinusoidal, bile canalicular, and lateral). Hepatocytes placed in monolayer culture re-established morphologically distinct plasma membrane regions analogous to the original three domains. The behavior of several domain-specific markers was studied in these cells. The asialoglycoprotein (ASGP) receptor, an integral membrane glycoprotein normally restricted at the surface to the sinusoidal domain in situ, was retained in both single hepatocytes (> 95%) and in cells after 24 hr in monolayer culture but at lower levels. Cytochemistry with asialo-oroso-mucoid-horseradish peroxidase …
Structure, Transcription And Evolution Of The Alu Family Of Interspersed Repetitive Dna Sequences, James Tilford Elder
Structure, Transcription And Evolution Of The Alu Family Of Interspersed Repetitive Dna Sequences, James Tilford Elder
Yale Medicine Thesis Digital Library
The cloning of DNA fragments derived from the (beta)-like globin gene cluster of normal and (beta)('+)-thalassemic individuals is described. These and other cloned human DNA fragments are employed to define the strucure and transcription of a family of interspersed, repetitive RNA polymerase III transcription units in human DNA. These data allow unequivocal identification of these transcription units with the Alu family of interspersed, repetitive DNA sequences. Comparison of these sequences to those of other primate and rodent interspersed repeats reveals that the primate sequence resembles in many respects a dimer of the rodent sequence. This striking interordinal divergence stands in …
Somatic Cell Genetic And Molecular Analysis Of Dna-Mediated Gene Transfer, Kenneth Michael Huttner
Somatic Cell Genetic And Molecular Analysis Of Dna-Mediated Gene Transfer, Kenneth Michael Huttner
Yale Medicine Thesis Digital Library
No abstract provided.
Development Of A Method For Measuring Amino Acid Transport In Cultured Cells Growing On Solid Surfaces, Jeffrey David Roth
Development Of A Method For Measuring Amino Acid Transport In Cultured Cells Growing On Solid Surfaces, Jeffrey David Roth
Yale Medicine Thesis Digital Library
No abstract provided.