Medicine and Health Sciences Commons^™

Egf Receptor Kinase Activity Is Required For Gap Junction Closure And For Part Of The Decrease In Ovarian Follicle Cgmp In Response To Luteinizing Hormone, Rachael P. Norris, Marina Freudzon, Viacheslav O. Nikolaev, Laurinda A. Jaffe

UCHC Articles - Research

The meiotic cell cycle in mouse oocytes is arrested in prophase, and then restarted when luteinizing hormone (LH) acts on the surrounding granulosa cells. The granulosa cells keep meiosis arrested by providing a source of cGMP that diffuses into the oocyte through gap junctions, and LH restarts the cell cycle by closing the junctions and by decreasing granulosa cell cGMP, thus lowering oocyte cGMP. Epidermal growth factor receptor (EGFR) activation is an essential step in triggering LH-induced meiotic resumption, but its relationship to the cGMP decrease in the follicle is incompletely understood, and its possible function in causing gap junction …

Mhc Class I And Tcr Avidity Control The Cd8 T Cell Response To Il-15/Il-15rα Complex, Thomas A. Stoklasek, Sara L. Colpitts, Henry M. Smilowitz, Leo Lefrançois

UCHC Articles - Research

IL-15 operates via a unique mechanism termed transpresentation. In this system, IL-15 produced by one cell type is bound to IL-15Rα expressed by the same cell and is presented to apposing cells expressing the IL-15Rβ/γC complex. We have shown that administering soluble IL-15Rα complexed with IL-15 can greatly enhance IL-15 activity. We now show that the naive CD8 T cell response to exogenous IL-15/IL-15Rα complex is MHC class I dependent. In the absence of β2 microglobulin, naive CD8 T cells scarcely proliferated in response to IL-15/IL-15Rα complex, whereas memory cells proliferated, although to a lesser extent, compared with levels in …

The Decade Of The Dendritic Nmda Spike, Srdjan D. Antic, Wen-Liang Zho, Anna R. Moore, Shaina M. Shor, Katerina D. Ikonomu

UCHC Articles - Research

In the field of cortical cellular physiology, much effort has been invested in understanding thick apical drites of pyramidal neurons and the regenerative sodium and calcium spikes that take place in the apical trunk. Here we focus on thin dendrites of pyramidal cells (basal, oblique, and tuft dendrites), and we discuss one relatively novel form of an electrical signal (“NMDA spike”) that is specific for these branches. Basal, oblique, and apical tuft dendrites receive a high density of glutamatergic synaptic contacts. Synchronous activation of 10–50 neighboring glutamatergic synapses triggers a local dendritic regenerative potential, NMDA spike/plateau, which is characterized by …

Determining Optimal Storage Arrangements For Open Access Data Sets, As For Nsf Data Management Plan Requirements, David B. Lowe

Published Works

Document is a proposed draft of a decision tree to be used in determining what approach to take for making data available in order to comply with open access requirements for data management, as per National Science Foundation requirements.

A Detailed Mathematical Model Predicts Serial Engagement Of Ige-Fcεri Complexes Can Enhance Syk Activation In Mast Cells, Michael L. Blinov

UCHC Articles - Research

The term serial engagement was introduced to describe the ability of a single peptide, bound to a MHC molecule, to sequentially interact with TCRs within the contact region between a T cell and an APC. In addition to ligands on surfaces, soluble multivalent ligands can serially engage cell surface receptors with sites on the ligand, binding and dissociating from receptors many times before all ligand sites become free and the ligand leaves the surface. To evaluate the role of serial engagement in Syk activation, we use a detailed mathematical model of the initial signaling cascade that is triggered when FcepsilonRI …

Crystal Structure Of The Gerbc Component Of A Bacillus Subtilis Spore Germinant Receptor, Yunfeng Li, Barbara Setlow, Peter Setlow, Bing Hao

UCHC Articles - Research

The nutrient germinant receptors (nGRs) of spores of Bacillus species are clusters of three proteins that play a critical role in triggering the germination of dormant spores in response to specific nutrient molecules. Here we report the crystal structure of the C protein of the GerB germinant receptor, so called GerBC, of Bacillus subtilis spores at 2.3 Å resolution. The GerBC protein adopts a previously uncharacterized type of protein fold consisting of three distinct domains, each of which is centered by a β sheet surrounded by multiple α helices. Secondary structure prediction and structure-based sequence alignment suggest that the GerBC …

Early Signals During Cd8+ T Cell Priming Regulate The Generation Of Central Memory Cells, Joshua J. Obar, Leo Lefrancois

UCHC Articles - Research

The CD8⁺ T cell response to infection is characterized by the appearance of short-lived (CD127^low killer cell lectin-like receptor G 1–high) and memory-precursor (CD127^high killer cell lectin-like receptor G 1–low) effector cells. How and when central-memory T (T_CM; CD62L^high CCR7⁺) cell and effector-memory T(T_EM; CD62L^low CCR7⁻) cell subsets are established remains unclear. We now show that the T_CM cell lineage represents an early developmental branchpoint during the CD8⁺ T cell response to infection. Central-memory CD8⁺ T cells could be identified prior to the peak …

Inhibitory Role Of Sphingosine 1-Phosphate Receptor 2 In Macrophage Recruitment During Inflammation, Jason Michaud, Timothy Hla, Dong-Soon Im

UCHC Articles - Research

Macrophage recruitment to sites of inflammation is an essential step in host defense. However, the mechanisms preventing excessive accumulation of macrophages remain relatively unknown. The lysophospholipid sphingosine 1-phosphate (S1P) promotes T and B cell egress from lymphoid organs by acting on S1P receptor 1 (S1P₁R). More recently, S1P₅R was shown to regulate NK cell mobilization during inflammation, raising the possibility that S1P regulates the trafficking of other leukocyte lineages. In this study, we show that S1P₂R inhibits macrophage migration in vitro and that S1P₂R-deficient mice have enhanced macrophage recruitment during thioglycollate peritonitis. …

Racial And Ethnic Disparities In Low Birth Weight Delivery Associated With Maternal Occupational Characteristics, John D. Meyer, Nicholas D. Warren, Susan T. Reisine

UCHC Articles - Research

Objectives

Work characteristics and maternal education have both been associated with low birth weight (LBW) delivery. We sought to examine the relative contribution of these two factors to LBW delivery and determine whether ethnic/racial differentials in educational attainment and work characteristics might play a role in well-described disparities in LBW.

Methods

Scores for work substantive complexity (SC) derived from the O*NET were imputed to maternal occupation for Connecticut singleton births in 2000. Risks for LBW were estimated separately for black, Hispanic, and white mothers using logistic regression controlling for maternal covariates.

Results

Using white mothers as a referent, working is …

Prognostic Value Of Ishak Fibrosis Stage: Findings From The Halt-C Trial, Herbert L. Bonkovsky

UCHC Articles - Research

Background and Aims

Studies of the prognostic value of Ishak fibrosis stage are lacking. We utilized multi-year follow-up of the Hepatitis C Antiviral Long Term Treatment Against Cirrhosis (HALT-C) Trial to determine whether individual Ishak fibrosis stages predicted clinical outcomes in patients with chronic hepatitis C.

Methods

Baseline liver biopsies from 1,050 patients with compensated chronic hepatitis C who had failed combination peginterferon and ribavirin were reviewed by a panel of expert hepatopathologists. Fibrosis was staged with the Ishak scale (ranging from 0=no fibrosis to 6=cirrhosis). Biopsy fragmentation and length as well as number of portal tracts were recorded. We …

Memory Cd8+ T Cell Differentiation, Joshua J. Obar, Leo Lefrancois

UCHC Articles - Research

In response to infection or effective vaccination, naive antigen-specific CD8+ T cells undergo a dramatic highly orchestrated activation process. Initial encounter with an appropriately activated antigen-presenting cell leads to blastogenesis and an exponential increase in antigen-specific CD8+ T cell numbers. Simultaneously, a dynamic differentiation process occurs, resulting in formation of both primary effector and long-lived memory cells. Current findings have emphasized the heterogeneity of effector and memory cell populations with the description of multiple cellular subsets based on phenotype, function, and anatomic location. Yet, only recently have we begun to dissect the underlying factors mediating the temporal control of the …

Use Of Virtual Cell In Studies Of Cellular Dynamics, Leslie M. Loew, Boris M. Slepchenko

UCHC Articles - Research

The Virtual Cell (VCell) is a unique computational environment for modeling and simulation of cell biology. It has been specifically designed to be a tool for a wide range of scientists, from experimental cell biologists to theoretical biophysicists. The models created with VCell can range from the simple, to evaluate hypotheses or to interpret experimental data, to complex multi-layered models used to probe the predicted behavior of spatially resolved, highly non-linear systems. In this Chapter, we discuss modeling capabilities of VCell and demonstrate representative examples of the models published by the Virtual Cell users.

Expansion Of The Eukaryotic Proteome By Alternative Splicing, Brenton R. Graveley

UCHC Articles - Research

The collection of components required to carry out the intricate processes involved in generating and maintaining a living, breathing and, sometimes, thinking organism is staggeringly complex. Where do all of the parts come from? Early estimates stated that about 100,000 genes would be required to make up a mammal; however, the actual number is less than one-quarter of that, barely four times the number of genes in budding yeast. It is now clear that the ‘missing’ information is in large part provided by alternative splicing, the process by which multiple different functional messenger RNAs, and therefore proteins, can be synthesized …