UV-dependent alternative splicing uncouples p53 activity and PIG3 gene function through rapid proteolytic degradation.

The p53-inducible gene 3 (PIG3) is a transcriptional target of the tumor suppressor protein p53 and is thought to play a role in apoptosis. In this report, we identify a novel alternatively spliced product from the PIG3 gene that we call PIG3AS (PIG3 alternative splice). PIG3AS results from alternative pre-mRNA splicing that skips exon 4 of the five exons included in the PIG3 transcript.

Monocyte surface-bound IL-15 can function as an activating receptor and participate in reverse signaling.

IL-15 is a short chain, four-alpha helix cytokine that shares some biological function with IL-2. One striking difference between IL-2 and IL-15 is the ability of monocytes to express IL-15 on their cell surface after activation. In the current study we have investigated the ability of human monocyte cell surface IL-15 to participate in reverse signaling.

Do psychosocial and study skill factors predict college outcomes? A meta-analysis.

This study examines the relationship between psychosocial and study skill factors (PSFs) and college outcomes by meta-analyzing 109 studies. On the basis of educational persistence and motivational theory models, the PSFs were categorized into 9 broad constructs: achievement motivation, academic goals, institutional commitment, perceived social support, social involvement, academic self-efficacy, general self-concept, academic-related skills, and contextual influences. Two college outcomes were targeted: performance (cumulative grade point average; GPA) and persistence (retention).

Differential distribution of the JC virus receptor-type sialic acid in normal human tissues.

JC virus (JCV), a member of the polyomavirus family, causes a demyelinating disease of the central nervous system (CNS) in humans known as progressive multifocal leukoencephalopathy. Although glial cells are the principal target of JCV productive infection in progressive multifocal leukoencephalopathy patients, little is known regarding the site of JCV persistence and the mechanisms by which the virus spreads to the CNS to cause disease. Previous work has demonstrated the presence of replicating JCV DNA in B lymphocytes from peripheral blood, tonsil, and spleen and it has been hypothesized that lymphocytes may be one site of JCV persistence.

Ephrin signaling: One raft to rule them all? One raft to sort them? One raft to spread their call and in signaling bind them?

The Eph receptor tyrosine kinases (RTK) and their membrane-bound ligands, the ephrins, mediate cell-contact-dependent signaling events that control multiple aspects of metazoan embryonic development. The ephrins and their receptors regulate cell movement that is essential for forming and stabilizing the spatial organization of tissues and cell types. This includes the guidance of migrating cells or neuronal growth cones to specific targets.

Screening for low literacy among adult caregivers of pediatric patients.

Background And Objectives: The association between functional illiteracy and poor health has led to pediatric literacy promotion programs in the primary care setting. These interventions do not address linked parental literacy needs. An obstacle to referring adults to literacy services is the lack of an instrument that can efficiently identify individuals who could benefit from such programs.

Vision testing in the pediatric population.

The goal of office testing of the child remains the same as it is for the adult--to gather as much information as efficiently as possible. Clinical testing of the child requires familiarity with the limitations available tests. Perhaps most important is the ability choose the proper test to use at every development stage.

Differential regulation of killer cell lectin-like receptor G1 expression on T cells.

The killer cell lectin-like receptor G1 (KLRG1) is the mouse homologue of the rat mast cell function-associated Ag and contains a tyrosine-based inhibitory motif in its cytoplasmic domain. It has been demonstrated that KLRG1 is induced on activated NK cells and that KLRG1 can inhibit NK cell effector functions. In this study, we show that in naive C57BL/6 mice KLRG1 is expressed on a subset of CD44(high)CD62L(low) T cells.

Outcomes of an integrated telehealth network demonstration project.

An integrated telehealth network that linked three hospitals, a federally qualified health care clinic with six sites, a county dental clinic, and patient homes was developed and implemented using both private and federal funding. The goal of the network was to deliver 10 different medical, dental, and behavioral health services to a rural community. The network served patients from nine different counties and two states.

Human fractalkine mediates leukocyte adhesion but not capture under physiological shear conditions; a mechanism for selective monocyte recruitment.

Fractalkine is a unique chemokine possessing a long mucin-like stalk and a transmembrane region that has been proposed to act as an adhesion molecule. We investigated the ability of fractalkine to recruit leukocytes from whole blood, using an immobilized fractalkine fusion protein in the parallel-plate flow-chamber assay. Significant adhesion of leukocytes to fractalkine peaked at 2 dynes/cm(2) but was minimal at 10 dynes/cm(2).

Deformation-based surface morphometry applied to gray matter deformation.

We present a unified statistical approach to deformation-based morphometry applied to the cortical surface. The cerebral cortex has the topology of a 2D highly convoluted sheet. As the brain develops over time, the cortical surface area, thickness, curvature, and total gray matter volume change.

Fibroblast growth factor-2-induced signaling through lipid raft-associated fibroblast growth factor receptor substrate 2 (FRS2).

The plasma membrane is not homogeneous but contains specific subcompartments characterized by their unique lipid and protein composition. Based on their enrichment in various signaling molecules, these membrane microdomains are recognized to be sites of localized signal transduction for a number of extracellular stimuli. We have previously shown that fibroblast growth factor-2 (FGF2) induced a specific signaling response within a lipid raft membrane microdomain in human neuroblastoma cells characterized by the tyrosine phosphorylation of a p80 phosphoprotein.

Src-family kinase signaling modulates the adhesion of Plasmodium falciparum on human microvascular endothelium under flow.

The pathogenicity of Plasmodium falciparum is due to the unique ability of infected erythrocytes (IRBCs) to adhere to vascular endothelium. We investigated whether adhesion of IRBCs to CD36, the major cytoadherence receptor on human dermal microvascular endothelial cells (HDMECs), induces intracellular signaling and regulates adhesion. A recombinant peptide corresponding to the minimal CD36-binding domain from P falciparum erythrocyte membrane protein 1 (PfEMP1), as well as an anti-CD36 monoclonal antibody (mAb) that inhibits IRBC binding, activated the mitogen-activated protein (MAP) kinase pathway that was dependent on Src-family kinase activity.

NK cell receptors: emerging roles in host defense against infectious agents.

Natural killer (NK) cells have the ability to become activated under the appropriate conditions by utilizing one or more cell surface receptors that are capable of inducing NK cell cytokine production and/or cytotoxicity. The expression of a variable array of inhibitory receptors on the surface of NK cells acts to counterbalance the positive signals initiated through activating receptors. Increasing evidence suggests an important role for both activating and inhibitory NK cell receptors in an appropriate and controlled NK response to infectious agents.

Evaluation of the 3D BacT/ALERT automated culture system for the detection of microbial contamination of platelet concentrates.

Bacterial transmission remains the major component of morbidity and mortality associated with transfusion-transmitted infections. Platelet concentrates are the most common cause of bacterial transmission. The BacT/ALERT 3D automated blood culture system has the potential to screen platelet concentrates for the presence of bacteria.

Project Eagle: techniques for multi-family psycho-educational group therapy with gifted American Indian adolescents and their parents.

This article describes Project Eagle, a model for short-term psycho-educational therapy with gifted and talented American Indian adolescents and their parents. Descriptions of Project Eagle s program organization as well as its culturally relevant techniques and activities are provided. The program evaluation includes: participant ratings of the activities, cultural relevance, feelings of being respected, interaction with parents and overall effectiveness of the program.

Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in ovarian granulosa cell tumors.

Granulosa cell tumors (GCTs) of the ovary are relatively rare and account for <5% of all ovarian cancers. The molecular pathogenesis of these tumors is not well understood. We tested the hypothesis that cyclin-dependent kinase inhibitors, specifically the inhibitors of the cyclin-dependent kinase 4 (INK4) family, are targets for altered gene expression in GCTs.

Comparing attentional bias to smoking cues in current smokers, former smokers, and non-smokers using a dot-probe task.

Much evidence documents that individuals with emotional and drug-use disorders demonstrate biased attention toward stimuli associated with their disorder. This bias appears to diminish following successful treatment. Two studies examined whether current cigarette smokers show biased attention toward smoking-related images compared with non-smokers (Studies 1 and 2) and whether this bias is less pronounced in former smokers (Study 2).

A randomized, double-blind, placebo-controlled safety study of high-dose dextromethorphan in methadone-maintained male inpatients.

The NMDA antagonist dextromethorphan hydrobromide (DM) may be useful in the treatment of opioid dependence, particularly as a means of reducing tolerance to methadone during replacement therapy. As a prelude to clinical efficacy studies, a randomized, double-blind, placebo-controlled study examined the safety of DM in combination with methadone in inpatient, opiate-dependent volunteers. Male participants received daily methadone (50-70 mg/day) and either DM (n=10) or placebo (n=5) during the 12-day active medication phase of the study.

Isolation and characterization of a novel, transforming allele of the c-Cbl proto-oncogene from a murine macrophage cell line.

The c-Cbl proto-oncogene acts as an E3 ubiquitin ligase via its RING finger domain to negatively regulate activated cellular signal transduction pathways. We have identified an aberrant Cbl-protein of approximately 95 kDa, which we have called p95Cbl, from the murine reticulum sarcoma cell-line, J-774. Cloning of the p95Cbl cDNA revealed that it contains a deletion resulting in the loss of 111 amino acids, eliminating two critical tyrosine residues in the linker region as well as the entire RING finger domain.

Profound differences in leukocyte-endothelial cell responses to lipopolysaccharide versus lipoteichoic acid.

We have investigated the effects of LPS from Escherichia coli, lipoteichoic acid (LTA), and peptidoglycan (PepG) from Staphylococcus aureus, and live S. aureus on leukocyte-endothelial interactions in vivo using intravital microscopy to visualize muscle microvasculature. Systemic vs local administration of LPS induced very different responses.

Membrane-anchored Cbl suppresses Hck protein-tyrosine kinase mediated cellular transformation.

The mammalian proto-oncogene Cbl and its cellular homologues in Caenorhabditis elegans (Sli-1) and Drosophila (D-Cbl) are negative regulators of some growth factor receptor signaling pathways. Herein we show that Cbl can negatively regulate another signaling molecule, namely theSrc-family kinase Hck by targeting it for degradation. Hck-mediated cellular transformation of murine fibroblasts is reverted by ectopic expression of a membrane-anchored allele of Cbl as assessed by the cellular morphology, suppression of anchorage independent growth, and an overall reduction in the total tyrosine phosphorylation levels within the cells.

Cutting edge: inhibitory functions of the killer cell lectin-like receptor G1 molecule during the activation of mouse NK cells.

The killer cell lectin-like receptor G1 (KLRG1) is the mouse homolog of the rat mast cell function-associated Ag and contains an immunoreceptor tyrosine-based inhibitory motif in its cytoplasmic domain. In this study we demonstrate that both pathogenic and nonpathogenic in vivo activation of NK cells induces the expression of KLRG1 on their cell surface. Upon infection with murine CMV, this induction peaks between days 5 and 7 with about 90% of the NK cells expressing KLRG1.