Phosphorylation of c-Fos at the C-terminus enhances its transforming activity.

c-Fos is phosphorylated by MAP kinase and the 90 kDa-ribosomal S6 kinase (RSK) in vitro at serines 362 and 374 (rat) which we demonstrate are major in vivo phosphorylation sites in early G1. We have constructed c-Fos mutants with these serines changed to aspartic acid residues (FosD) to mimic phosphorylation or to alanine residues (FosA) to prevent phosphorylation. Cells expressing FosD exhibited a more extensive transformed phenotype than those expressing either FosA or wild type c-Fos (FosWT).

Visual specificity effects on word stem completion: beyond transfer appropriate processing?

An important, but poorly understood, aspect of memory retrieval concerns the conditions under which priming is influenced by perceptual changes in the form of target items. According to transfer appropriate processing perspectives, perceptual specificity effects on priming require a study task that focuses attention on the perceptual, rather than semantic, features of the items. Other research suggests that perceptual specificity effects are enhanced by conditions yielding high levels of explicit memory.

Ubiquitinylation of transcription factors c-Jun and c-Fos using reconstituted ubiquitinylating enzymes.

Recombinant c-Jun and c-Fos were ubiquitinylated by the ubiquitin carrier enzymes E214K, E220K, or E232K in the presence of the ubiquitin-activating enzyme, E1. Addition of ubiquitin protein ligase E3 substantially enhanced the E214K-mediated ubiquitinylation of c-Jun and c-Fos. Truncated c-Jun and c-Fos mutant proteins including wbJun and wbFos were also ubiquitinylated under the same conditions, suggesting the sites of ubiquitinylation are located within the dimerization and DNA binding domains of c-Jun and c-Fos.

Genetic analysis of thyroid hormone receptors in development and disease.

Thyroid hormone (T3) fulfills diverse functions in vertebrate development and physiology. These functions are thought to be mediated by two genes encoding the related T3 receptors. TR alpha and TR beta.

Spontaneous and evoked glutamate signalling influences Fos-lacZ expression and pyramidal cell death in hippocampal slice cultures from transgenic rats.

Previously, we established that a spatially and temporally predictable pattern of spontaneous cell death occurs in pyramidal hippocampal neurons maintained in organotypic slice cultures. We have begun to examine the signalling events that may be relevant to this process by analyzing the expression of cellular immediate-early genes (cIEGs). In the present studies, organotypic hippocampal cultures were generated from transgenic rats that carry a fos-lacZ fusion gene.

Arginine deiminase system and acid adaptation of oral streptococci.

Streptococcus rattus FA-1 and Streptococcus sanguis NCTC 10904 underwent phenotypic acid adaptation in batch cultures toward the end of sugar-fueled growth after the culture pH had dropped to triggering values. The bacteria could be derepressed or induced for arginine deiminase independently of acid adaptation, and arginolysis afforded protection against acid killing over and above that of acid adaptation.

Absence of mutations in superoxide dismutase and catalase genes in patients with Parkinson's disease.

Background: Parkinson's disease (PD) is an adult-onset, neurodegenerative disorder characterized by a selective loss of the dopaminergic cells of the substantia nigra and by progressive motor decline. Studies have shown aberrant oxidative stress metabolism within the substantia nigra and other dopaminergic regions of the brain in patients with PD.

Objective: To screen the genes of three free radical detoxifying enzymes--copper/zinc superoxide dismutase, manganese superoxide dismutase, and catalase--for mutations in patients with PD.

Use of fluorescence resonance energy transfer to estimate intramolecular distances in the Msx-1 homeodomain.

We have utilized fluorescence resonance energy transfer (FRET) to investigate the spatial proximities of segments in the Msx-1 homeodomain (Msx). This strategy makes use of a single, invariant tryptophan (Trp-48) in helix III as the donor for FRET. The acceptor molecule, 5-[[[(iodoacetyl)amino]-ethyl]amino]naphthalene-1-sulfonic acid (AEDANS), was incorporated into Msx at positions 6, 10, or 27 which are within the N-terminal arm, and helices I and II since these segments have been implicated in interactions with helix III.

Minimizing donor blood exposure in the neonatal intensive care unit. Current trends and future prospects.

Limitations in the knowledge of the pathophysiology of anemia contribute to unfounded and liberal transfusion practices in the preterm infant and to uncertain risk-benefit ratios. Researchers have explored an array of strategies to minimize transfusions. Such strategies include collection and banking of autologous placental blood, administration of recombinant erythropoietin, innovations in blood banking practices, and improved definitions of the markers of anemia with more rigorous transfusion guidelines.

N-terminal variants of thyroid hormone receptor beta: differential function and potential contribution to syndrome of resistance to thyroid hormone.

The human syndrome of resistance to thyroid hormone (RTH) is associated with dominant mutations in the thyroid hormone receptor beta (TR beta) gene that generate mutant receptors with impaired binding for T3. Although the TR beta gene differentially expresses two N-terminal variant receptors, TR beta 1 and TR beta 2, functional analyses of RTH mutants have focused exclusively on TR beta 1. Since TR beta 2 is expressed in tissues that are malfunctional in RTH, the role of mutations in the context of TR beta 2 was examined.

Kainic acid-induced neuronal death is associated with DNA damage and a unique immediate-early gene response in c-fos-lacZ transgenic rats.

Previously, we established that persistent upregulation of c-fos expression preceded kainic acid (KA)-induced neuronal death in mice. To discriminate between events that are products of the seizures elicited by KA and those that are specifically associated with its neurotoxic actions, we have examined the expression of cellular immediate-early genes (cIEGs) following KA or pentylenetetrazol (PTZ) treatment in c-fos-lacZ transgenic rats. While both chemoconvulsants elicit seizures, only KA causes selective neuronal death.

Violations of the independence assumption in process dissociation.

L. L. Jacoby, J.

A protein related to extracellular matrix proteins deleted in the mouse mutant reeler.

The autosomal recessive mouse mutation reeler leads to impaired motor coordination, tremors and ataxia. Neurons in affected mice fail to reach their correct locations in the developing brain, disrupting the organization of the cerebellar and cerebral cortices and other laminated regions. Here we use a previously characterized reeler allele (rl(tg)) to close a gene, reelin, deleted in two reeler alleles.

Fos: an immediate-early transcription factor in neurons.

In the past several years a great deal of evidence has accumulated linking neuronal activation events to the regulation of gene expression. We have pursued an analysis of c-fos regulation in the nervous system to elucidate the molecular mechanisms involved in stimulus-transcription coupling. The c-fos gene can be viewed as an archetype of the set of cellular immediate-early genes encoding transcription factors.

When encoding fails: instructions, feedback, and registration without learning.

Four experiments replicated and extended the registration-without-learning effect, in which there is little improvement in the ability to discriminate an old target (X) from a highly similar test item (Y) after the first few presentations of X, even though judgments of frequency continue to rise in an open-ended fashion. Forced-choice testing revealed the anomalous form of the learning curve for X-Y discrimination (faster and then slower than the exponential). Effects of several different learning instructions were compared, but these appeared to affect only the level of initial learning, and to do little to promote X-Y discrimination learning on later presentations.

Regulation of c-fos expression in transgenic mice requires multiple interdependent transcription control elements.

Transcription control regions of eukaryotic genes contain multiple sequence elements proposed to function independently to regulate transcription. We developed transgenic mice carrying fos-lacZ fusion genes with clustered point mutations in each of several distinct regulatory sequences: the sis-inducible element, the serum response element, the fos AP-1 site, and the calcium/cAMP response element. Analysis of Fos-lacZ expression in the CNS and in cultured cells demonstrated that all of the regulatory elements tested were required in concert for tissue- and stimulus-specific regulation of the c-fos promoter.

The effect of cholecystokinin-octapeptide on the hepatobiliary dysfunction caused by total parenteral nutrition.

Purpose: Patients on total parenteral nutrition (TPN) commonly have hepatobiliary dysfunction. Interruption of the enterohepatic circulation (EHC) and gallbladder stasis are part of the pathogenesis. Cholecystokinin-octapeptide (CCK-OP), by emptying the gallbladder, stimulates the EHC.

Inhibition of streptococcal growth, F-ATPase and pyrophosphatase by diphosphonates.

1-Hydroxyethane-1,1-diphosphonate (EHDP) and a variety of other diphosphonates, and also pyrophosphate, at millimolar levels were found to inhibit the growth of Streptococcus mutans GS-5. Inhibition appeared to be due mainly to chelation of Mg2+ and could be readily reversed through addition of Mg2+, or less effectively, by other divalent cations. The trianionic forms of the diphosphonates or pyrophosphate were more effective inhibitors than the dianionic forms.