Cell and Developmental Biology Commons^™

The Yeast Nuclear Pore Complex Functionally Interacts With Components Of The Spindle Assembly Checkpoint, Tatiana Louk, Oliver Kerscher, Robert J. Scott, Munira A. Basrai, Richard W. Wozniak

Arts & Sciences Articles

Aphysical and functional link between the nuclear pore complex (NPC) and the spindle checkpoint machinery has been established in the yeast Saccharomyces cerevisiae. We show that two proteins required for the execution of the spindle checkpoint, Mad1p and Mad2p, reside predominantly at the NPC throughout the cell cycle. There they are associated with a subcomplex of nucleoporins containing Nup53p, Nup170p, and Nup157p. The association of the Mad1p–Mad2p complex with the NPC requires Mad1p and is mediated in part by Nup53p. On activation of the spindle checkpoint, we detect changes in the interactions between these proteins, including the release of …

Historical Development Of The Linear Nonthreshold Dose-Response Model As Applied To Radiation, Ronald L. Kathren

The University of New Hampshire Law Review

[Excerpt] "Despite the nearly universal adoption of the linear nonthreshold dose response model (LNT) as the primary basis for radiation protection standards for the past half century, the LNT remains highly controversial and a contentious topic of discussion among health physicists, radiation biologists, and other radiological scientists. Indeed, it has been pointed out that the LNT has assumed the status of a paradigm, synonymous with an ideal, standard, or paragon or perhaps to some, a sacred cow. Reduced to its very basics, the LNT postulates that every increment of ionizing radiation dose, however small, carries with it a commensurate increase …

Shar-Pei Mediates Cell Proliferation Arrest During Imaginal Disc Growth In Drosophila, Madhuri Kango-Singh, Riitta Nolo, Chunyao Tao, Patrik Verstreken, P. Robin Hiesinger, Hugo J. Bellen, Georg Halder

Biology Faculty Publications

During animal development, organ size is determined primarily by the amount of cell proliferation, which must be tightly regulated to ensure the generation of properly proportioned organs. However, little is known about the molecular pathways that direct cells to stop proliferating when an organ has attained its proper size. We have identified mutations in a novel gene, shar-pei, that is required for proper termination of cell proliferation during Drosophila imaginal disc development. Clones of shar-pei mutant cells in imaginal discs produce enlarged tissues containing more cells of normal size. We show that this phenotype is the result of both …

Diet, Obesity And Reflux In The Etiology Of Adenocarcinomas Of The Esophagus And Gastric Cardia In Humans, Susan Mayne, Stephanie A. Navarro Silvera

Department of Public Health Scholarship and Creative Works

Incidence rates for esophageal adenocarcinoma have increased >350% since the mid-1970s. Rates for gastric cardia adenocarcinoma have also increased, although less steeply. This led to the initiation of large population-based case-control studies, particularly in the United States and Sweden, aimed at identifying risk factors for these cancers. Results have been emerging from these studies, with the consistent finding that obesity and gastroesophageal reflux disease are important risk factors for these cancers. Analyses of dietary factors are also available and indicate that diets high in total fat, saturated fat and cholesterol are associated with an increased risk of these cancers, whereas …

Anisomycin Activates Jnk And Sensitises Du 145 Prostate Carcinoma Cells To Fas Mediated Apoptosis, James Curtin, Thomas Cotter

Articles

Treatment of the hormone refractory prostate cancer cell line DU 145 with sublethal concentrations of chemotherapeutic drugs has been reported to sensitise these cells to Fas mediated apoptosis. However, the mechanism by which this occurs has not been determined. Our group has shown that inhibition of JNK activity completely abrogates the effects of chemotherapeutic drugs. Using anisomycin, a potent JNK agonist, we have demonstrated a role for JNK in Fas mediated apoptosis in DU 145 cells. Inhibition of Caspase 8 and Caspase 9 completely inhibits this process which suggests that DU 145 cells require mitochondrial amplification of the Fas apoptotic …

Decoding Cis-Regulatory Dnas In The Drosophila Genome, Michele Markstein, Michael Levine

Michele Markstein

Cis-regulatory DNAs control the timing and sites of gene expression during metazoan development. Changes in gene expression are responsible for the morphological diversification of metazoan body plans. However, traditional methods for the identification and characterization of cis-regulatory DNAs are tedious. During the past year, computational methods have been used to identify novel cis-DNAs within the entire Drosophila genome. These methods change the way that cis-DNAs will be analyzed in future studies and offer the promise of unraveling complex gene networks.

A Mathematical Model Of Bacterial Aerotaxis, Borbala Mazzag, Alex Mogilner

Borbala Mazzag

No abstract provided.

Endocytic Intermediates Involved With The Intracellular Trafficking Of A Fluorescent Cellular Prion Protein, Ac Magalhaes, Ja Silva, Vr Martins, Vf Prado, Ssg Ferguson, Mv Gomez, Rr Brentani, Mam Prado

Anatomy and Cell Biology Publications

We have investigated the intracellular traffic of PrPc, a glycosylphosphatidylinositol (GPI)-anchored protein implicated in spongiform encephalopathies. A fluorescent functional green fluorescent protein (GFP)-tagged version of PrPc is found at the cell surface and in intracellular compartments in SN56 cells. Confocal microscopy and organelle-specific markers suggest that the protein is found in both the Golgi and the recycling endosomal compartment. Perturbation of endocytosis with a dynamin I-K44A dominant-negative mutant altered the steady-state distribution of the GFP-PrPc, leading to the accumulation of fluorescence in unfissioned endocytic intermediates. These pre-endocytic intermediates did not seem to accumulate GFP-GPI, a minimum GPI-anchored protein, suggesting that …

The Tadpole Of Proceratophrys Avelinoi (Anura: Leptodactylidae), Rafael O. De Sá, José A. Langone

Biology Faculty Publications

The genus Proceratoprhys is poorly known. It consists of 14 currently recognized species (Frost, 2000) of medium-sized frogs distributed from northeastern Argentina and Paraguay to southeast Amazonia (Rondonia State), eastern and southern Brazil Proceratophrys avelinoi was described from Misiones, Argentina (Mercadal de Barrio and Barrio, 1993). The larval stage of this species is unknown. Herein, we describe the tadpole and the characteristics of the internal oral anatomy of P. avelinoi using scanning electron microscopy (SEM).

The Tadpole Of Proceratophrys Avelinoi (Anura: Leptodactylidae), Rafael O. De Sá, José A. Langone

Biology Faculty Publications

The genus Proceratoprhrys is poorly known. It consists of 14 currently recognized species (Frost, 2000) of medium-sized frogs distributed from northeastern Argentina and Paraguay to southeast Amazonia (Rondonia State), eastern and southern Brazil. Proceratophrys avelinoi was described from Misiones, Argentina (Mercadal de Barrio and Barrio, 1993). The larval stage of this species is unknown. Herein, we describe the tadpole and the characteristics of the internal oral anatomy of P avelinoi using scanning electron micros- copy (SEM).

Eye Suppression, A Novel Function Of Teashirt, Requires Wingless Signaling, Amit Singh, Madhuri Kango-Singh, Y. Henry Sun

Biology Faculty Publications

Teashirt (tsh) encodes a Drosophila zinc-finger protein. Misexpression of tsh has been shown to induce ectopic eye formation in the antenna. We report that tsh can suppress eye development. This novel function of tsh is due to the induction of homothorax (hth), a known repressor of eye development, and requires Wingless (WG) signaling. Interestingly, tsh has different functions in the dorsal and ventral eye, suppressing eye development close to the ventral margin, while promoting eye development near the dorsal margin. It affects both growth of eye disc and retinal cell differentiation.

Within-Litter Birth Weight Variation In The Domestic Pig And Its Relation To Pre-Weaning Survival, Weight Gain, And Variation In Weaning Weights, Barry N. Milligan, David Fraser, Donald L. Kramer

Ontogeny Collection

To determine the relationship between within-litter birth weight variation and pre-weaning survival and weight gain, and to provide practical guidance on fostering low-birth-weight piglets, we analyzed piglet survival and weight gain in litters of piglets from 52 sows followed through eight consecutive parities. Litters with high variation in birth weight had more deaths, especially if the litter’s mean birth weight was low. High variation in birth weight was also associated with high variation in weaning weight, but was not significantly related to mean weaning weight. Piglets with birth weights well below the range of most of the litter (‘low-birth-weight piglets’) …

Jun Dimerization Protein 2 Functions As A Progesterone Receptor N-Terminal Domain Coactivator, James S. Adelman, Suzanne E. Wardell, Viroj Boonyaratanakornkit, Ami Aronheim

James S. Adelman

The progesterone receptor (PR) contains two transcription activation function (AF) domains, constitutive AF-1 in the N terminus and AF-2 in the C terminus. AF-2 activity is mediated by a hormone-dependent interaction with a family of steroid receptor coactivators (SRCs). SRC-1 can also stimulate AF-1 activity through a secondary domain that interacts simultaneously with the primary AF-2 interaction site. Other protein interactions and mechanisms that mediate AF-1 activity are not well defined. By interaction cloning, we identified an AP-1 family member, Jun dimerization protein 2 (JDP-2), as a novel PR-interacting protein. JDP-2 was first defined as a c-Jun interacting protein that …

Involvement Of Platelet-Derived Growth Factor, Pdgf Receptor Signaling, Focal Adhesion Kinase And Src In Pressure-Induced Vascular Smooth Muscle Hypertrophy, Darian Clark Rice

Theses and Dissertations in Biomedical Sciences

Elevated blood pressure is associated with varying degrees of arterial remodeling. The mechanisms by which extracellular mechanical stress is converted into intracellular alterations in signal transduction and gene expression have yet to be fully elucidated. Our goal was to investigate the early events in the vascular smooth muscle response to acute hypertension and to identify mediators involved in long-term hypertensive remodeling.

In the acute phase of hypertension we targeted cell surface integrin and growth factor receptors thought to be mechanically sensitive. The signaling molecules FAK, Src and ERK-MAPK are known to be triggered by integrin engagement and growth factor receptor …

Terminal Deoxynucleotidyl Transferase Generation Of Sequence Diversity On Plasmids, Qingbei Zhang

Morehead State Theses and Dissertations

A thesis presented to the faculty of the College of Science and Technology at Morehead State University in partial fulfillment of the requirements for the Degree of Master of Science by Qingbei Zhang on June 19, 2002.

Inducible Gene Expression In Cell Cultures And In Microencapsulated Cells, Yong Yu

Loma Linda University Electronic Theses, Dissertations & Projects

The mifepristone-regulated transcriptional activation system provides a means to exogenously control gene expression in transformed mammalian cells in a temporal and spatial fashion. Such a promoter activation system consists of three components: The first of these is a steroidal inducer drug, mifepristone. This drug binds to the second component, a chimeric transcription factor complex, consisting of the mutant human progesterone receptor fused to the yeast GAL4 DNA-binding domain and the Herpes simplex virus protein VP 16 activation domain. The third component is a synthetic promoter, consisting of a series of GAL4 recognition sequences upstream of the adenovirus major late E1B …

Expression Of Gp73, A Resident Golgi Membrane Protein, In Viral And Nonviral Liver Disease, Raleigh D. Kladney, Xiaoyen Cui, Gary A. Bulla, Elizabeth M. Brunt, Claus J. Fimmel

Gary A. Bulla

GP73 is a novel type II Golgi membrane protein of unknown function that is expressed in the hepatocytes of patients with adult giant-cell hepatitis (Gene 2000;249:53-65). Its expression pattern in human liver disease and the regulation of its expression in hepatocytes have not been systematically studied. The aims of the present study were to compare GP73 protein levels in viral and nonviral human liver disease and in normal livers, to identify its cellular sources, and to study the regulation of its expression in hepatoma cells in vitro. GP73 protein levels were quantitated in explant livers of patients with well-defined disease …

Expression Of Gp73, A Resident Golgi Membrane Protein, In Viral And Nonviral Liver Disease, Raleigh Kladney, Xiaoyen Cui, Gary Bulla, Elizabeth Brunt, Claus Fimmel

Faculty Research & Creative Activity

GP73 is a novel type II Golgi membrane protein of unknown function that is expressed in the hepatocytes of patients with adult giant-cell hepatitis (Gene 2000;249:53-65). Its expression pattern in human liver disease and the regulation of its expression in hepatocytes have not been systematically studied. The aims of the present study were to compare GP73 protein levels in viral and nonviral human liver disease and in normal livers, to identify its cellular sources, and to study the regulation of its expression in hepatoma cells in vitro. GP73 protein levels were quantitated in explant livers of patients with well-defined disease …

Expression Of Gp73, A Resident Golgi Membrane Protein, In Viral And Nonviral Liver Disease, Raleigh D. Kladney, Xiaoyen Cui, Gary A. Bulla, Elizabeth M. Brunt, Claus J. Fimmel

Faculty Research & Creative Activity

GP73 is a novel type II Golgi membrane protein of unknown function that is expressed in the hepatocytes of patients with adult giant-cell hepatitis (Gene 2000;249:53-65). Its expression pattern in human liver disease and the regulation of its expression in hepatocytes have not been systematically studied. The aims of the present study were to compare GP73 protein levels in viral and nonviral human liver disease and in normal livers, to identify its cellular sources, and to study the regulation of its expression in hepatoma cells in vitro. GP73 protein levels were quantitated in explant livers of patients with well-defined disease …

Mechanisms Of Autoantigen Cleavage During Cell Death, Xiwei Wu

Loma Linda University Electronic Theses, Dissertations & Projects

Specific intracellular autoantigens targeted by autoantibodies in systemic autoimmune and chronic inflammatory diseases undergo posttranslational modifications, such as cleavage, during cell death that could potentially enhance their immunogenicity. In light of the increasing interest in the immunological consequences of defective clearance of apoptotic cells, we explored whether autoantigens cleaved during apoptosis undergo an additional wave of proteolysis as apoptosis progresses to secondary necrosis in the absence of phagocytosis. Jurkat T cells treated with different apoptosis inducers underwent a rapid apoptosis that gradually progressed to secondary necrosis. During the initial apoptotic stages, several nuclear autoantigens, including PARP, Topo I, and LEDGF/p75 …

Characterizing Gene Expression During Lens Formation In Xenopus Laevis: Evaluating The Model For Embryonic Lens Induction, Brian Walter, Jonathan Henry, Maria Carinato, Jonathan Schaefer, Adam Wolfe, Brian Walter, Kimberly Perry, Tricia Elbl

Brian Walter

Few directed searches have been undertaken to identify the genes involved in vertebrate lens formation. In the frog Xenopus, the larval cornea can undergo a process of transdifferentiation to form a new lens once the original lens is removed. Based on preliminary evidence, we have shown that this process shares many elements of a common molecular/genetic pathway to that involved in embryonic lens development. A subtracted cDNA library, enriched for genes expressed during cornea-lens transdifferentiation, was prepared. The similarities/identities of specific clones isolated from the subtracted cDNA library define an expression profile of cells undergoing cornea-lens transdifferentiation ("lens regeneration") and …

The Effect Of Butyrate Feeding On Skeletal Muscle And Adipose Tissue Glucose Uptake, Sean Eric Thatcher

Morehead State Theses and Dissertations

A thesis presented to the faculty of the College of Science and Technology at Morehead State University in partial fulfillment of the requirements for the Degree of Master of Science in Biology by Sean Eric Thatcher on May 31, 2002.

Searching For The Middle Ground: Mechanisms Of Chromosome Alignment During Mitosis, Tarun M. Kapoor, Duane A. Compton

Dartmouth Scholarship

The contributions of key molecules predicted to align chromosomes at the center of the mitotic spindle have been recently examined. New results dictate that models for how chromosomes align during the early stages of mitosis must be revised to integrate properties of microtubule-based motor proteins as well as microtubule dynamics.

The Role Of The Arabidopsis Phosphatidylinositol 3-Kinase In Vacuolar Protein Transport, Christopher A. Jones

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

In all eukaryotic organisms vesicle-mediated protein transport is crucial for maintaining cellular homeostasis. Over the past decade significant strides have been made in elucidating the molecular mechanisms governing this complex process. Both genetic and biochemical studies have demonstrated the unequivocal involvement of class III phospatidylinositol 3-kinases (PtdIns 3-kinases) in regulating vesicle transport. While PtdIns 3-kinases have been well studied in both yeast and mammalian systems, the role of these enzymes in plants is poorly understood. In the present study, we demonstrate that the Arabidopsis Ptdlns 3-kinase is localized to the cytoplasm, and perhaps the Golgi apparatus. Moreover, we show that …

The Biophysics Of Leaf Growth In Salt-Stressed Barley. A Study At The Cell Level., Wieland Fricke, Winfried Peters

Winfried S. Peters

Composition And Method For The Prevention And Treatment Of Oxidative Damage In Ocular Tissues, Marjorie F. Lou, Nalini Raghavachari;, Fengyu Qiao

School of Veterinary and Biomedical Sciences: Faculty Publications

Thioltransferase and derivatives thereof are provided. Methods of treating or preventing cataract formation comprosing administering thioltransferase or a derivative thereof are also provided. Thioltransferase or derivatives thereof are also useful for treating or preventing diseases resulting from or associated with oxidative stress. Human lens thioltransferase and a DNA sequence encoding the same are also provided.

A Cycle Of Vam7p Release From And Ptdins 3-P–Dependent Rebinding To The Yeast Vacuole Is Required For Homotypic Vacuole Fusion, Christine Boeddinghaus, Alexey J. Merz, Rico Laage, Christian Ungermann

Dartmouth Scholarship

Vacuole fusion requires a coordinated cascade of priming, docking, and fusion. SNARE proteins have been implicated in the fusion itself, although their precise role in the cascade remains unclear. We now report that the vacuolar SNAP-23 homologue Vam7p is a mobile element of the SNARE complex, which moves from an initial association with the cis-SNARE complex via a soluble intermediate to the docking site. Soluble Vam7p is specifically recruited to vacuoles and can rescue a fusion reaction poisoned with antibodies to Vam7p. Both the recombinant Vam7p PX domain and a FYVE domain construct of human Hrs block the recruitment of …

Prostate Specific Membrane Antigen (Psma): Immunoassay Development And Characterization Of Transcriptional Regulation, Zhen Xiao

Theses and Dissertations in Biomedical Sciences

Prostate cancer (PCA) is the most common cancer and the second leading cause of death among American men. The high mortality is greatly attributed to the lack of early detection tools and effective treatment for metastasis and relapses. Biomarkers that can discriminate benign from malignant tumor and signal the development of androgen independent and metastatic tumor are needed. A biomarker designated prostate specific membrane antigen (PSMA) has the potential to fulfill this need. The objective of this study is to develop a clinically useful immunoassay for quantitation of serum PSMA and to study the molecular mechanism underlying the upregulation of …

The Expression Of The Let-7 Small Regulatory Rna Is Controlled By Ecdysone During Metamorphosis In Drosophila Melanogaster, Lorenzo Sempere, Edward Dubrovsky, Veronica Dubrovskaya, Edward Berger, Victor Ambros

Victor R. Ambros

In Caenorhabditis elegans, the heterochronic pathway controls the timing of developmental events during the larval stages. A component of this pathway, the let-7 small regulatory RNA, is expressed at the late stages of development and promotes the transition from larval to adult (L/A) stages. The stage-specificity of let-7 expression, which is crucial for the proper timing of the worm L/A transition, is conserved in Drosophila melanogaster and other invertebrates. In Drosophila, pulses of the steroid hormone 20-hydroxyecdysone (ecdysone) control the timing of the transition from larval to pupal to adult stages. To test whether let-7 expression is regulated by ecdysone …

Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky

Dartmouth Scholarship

All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor α (RARα). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARα, a repressor of RA target genes, abolished this UBE1L promoter activity. A hallmark of …