Asyntactic thematic role assignment: the use of a temporal-spatial strategy.

We report syntactic comprehension performance of a left-handed man with a right-hemisphere infarct. He was unable to accurately map grammatical categories (subject, object) onto thematic roles (agent, patient), despite demonstrating intact conceptual knowledge of these thematic roles. He performed poorly on both active and passive reversible sentences.

Tau self-association: stabilization with a chemical cross-linker and modulation by phosphorylation and oxidation state.

tau is a major component of paired helical filaments found in the neurofibrillary tangles of Alzheimer's diseased brain. However, the mechanism or mechanisms responsible for the association of tau to form these aggregates remains unknown. In this study, the role of intermolecular disulfide bonds in the formation of higher order oligomers of bovine tau and the human recombinant tau isoform T3 was examined using the chemical cross-linking agent disuccinimidylsuberate (DSS).

Pertussis toxin-sensitive G protein alpha-subunits: production of monoclonal antibodies and detection of differential increases on differentiation of PC12 and LA-N-5 cells.

Monoclonal antibodies were produced that are specific for the three major pertussis toxin-sensitive G protein alpha-subunits present in mammalian brain--alpha o, alpha i1, and alpha i2--using purified bovine brain G proteins, purified rat brain G proteins, and purified recombinant alpha i2, respectively. These monoclonal antibodies were used to monitor changes in the concentrations of the three G protein alpha-subunits during differentiation of PC12 cells and human neuroblastoma LA-N-5 cells. In PC12 cells, levels of alpha i1 but not alpha i2 increased during nerve growth factor-induced differentiation.

Diurnal variation in kainate-induced AP-1 activation in rat brain: influence of glucocorticoids.

The large diurnal rhythm of circulating glucocorticoid levels was used to determine if physiological fluctuations of glucocorticoids were capable of modulating kainate-induced immediate early gene (IEG) activation, measured as AP-1 DNA binding activity, in rat brain since administered dexamethasone previously had been shown to be inhibitory. AP-1 activity in the cerebral cortex 1.5 h after kainate treatment measured at 08.

[3H]PtdIns hydrolysis in postmortem human brain membranes is mediated by the G-proteins Gq/11 and phospholipase C-beta.

A method utilizing exogenously added [3H]PtdIns incubated with membranes prepared from postmoretem human brain has been shown to provide a means of measuring agonist-induced, guanosine 5'-O-(thiotriphosphate) (GTP[S])-dependent hydrolysis of [3H]PtdIns, thus allowing investigations of the activity of the phosphoinositide second-messenger system in accessible human brain tissue. Agonists inducing [3H]PtdIns hydrolysis include carbachol, trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD; a glutamatergic metabotropic receptor agonist), serotonin and ATP, with the latter two agonists producing the largest responses. In addition to ATP, [3H]PtdIns hydrolysis was induced by ADP and by 2-methylthio-ATP, indicating that P2-purinergic receptors mediate this process.

Monoclonal antibody Alz-50 reacts with bovine and human serum albumin.

Alz-50, a monoclonal antibody originally prepared using Alzheimer brain homogenates, reacts with PHF-tau and normal tau on immunoblots, and stains specific neuronal populations in sections from Alzheimer's disease brain. Although the Alz-50 epitope has been mapped to amino acids 2-10 present in all human tau isoforms, minimal Alz-50 immunoreactivity is present in tissue from control brain, suggesting Alz-50 binding may be dependent on tau conformational differences. The absence of conclusive results concerning Alz-50 binding presents the possibility of Alz-50 immunoreactivity with proteins other than tau.

Compromised mitochondrial function results in dephosphorylation of tau through a calcium-dependent process in rat brain cerebral cortical slices.

Mitochondria play an important role in modulating intracellular levels of calcium, and therefore compromised mitochondrial function often leads to disruptions in calcium homeostasis. In this study, the effects of two uncouplers of oxidative phosphorylation, carbonyl cyanide-3-chlorophenylhydrazone (CCCP) and p-trifluoromethoxyphenylhydrazone (FCCP), on calcium-mediated modifications of the microtubule-associated protein, tau, in rat brain slices were examined. Incubation of slices with CCCP or FCCP resulted in an increase in electrophoretic mobility of several of the tau isoforms, with no apparent loss of intact tau or the appearance of degradation products.

Transglutaminase facilitates the formation of polymers of the beta-amyloid peptide.

One of the major pathological characteristics of Alzheimer's disease is the increased number of amyloid-containing senile plaques within the brain. The dense cores of these plaques are composed primarily of highly insoluble aggregates of a 39-43-residue peptide referred to as the beta-amyloid peptide (beta A). The mechanisms by which these insoluble extracellular deposits of beta A are formed remain unknown.

Dexamethasone attenuates kainate-induced AP-1 activation in rat brain.

The goal of this investigation was to determine if administration of the synthetic glucocorticoid dexamethasone modulates rat brain AP-1 DNA binding activity. Treatment with the selective excitatory amino acid agonist kainate was used to activate AP-1 formation. Kainate (12 mg/kg) administration induced a biphasic activation of AP-1 in rat cerebral cortex and hippocampus with maximal levels observed at 1.

Role for animal research in the investigation of human mental retardation.

Animal models of the cognitive deficiency states of mental retardation per se are underutilized. A general learning impairment model and a reasoning/insight model, both in rats, were reviewed for parallels to theories of human cognitive deficiency. Predictions were made for the relevance to human mental retardation.

Lithium potentiates phosphoinositide-linked 5-HT receptor stimulation in vivo.

The therapeutic effect of lithium in manic-depressive illness may involve alterations in the activity of the phosphoinositide second messenger system. Lithium administration to rats potentiates responses to cholinergic agonists, as evidenced by the production of seizures in lithium-treated rats after normally nonconvulsant doses of cholinergic agonists. We now report that lithium also potentiates the response to a serotonin (5-HT) agonist, DOI, that activates 5-HT2/5-HT1C receptors coupled to phosphoinositide hydrolysis.

Home environment of mothers with mental retardation.

A prospective study of 38 mothers with IQs less than 75 and 27 mothers with IQs over 85 who were also low income was conducted. This study was designed to distinguish between children's developmental risk associated with maternal disability and risk related primarily to poverty. Findings from administration of the HOME inventory showed that mothers with intellectual limitations had significantly lower scores, indicating greater developmental risk for their children due to environmental deprivation.

The volume of the cerebellar molecular layer predicts attention to novelty in rats.

Cerebellum volume was compared with the behavioral measure of attention to novelty in normal rats. The volume of the cerebellar molecular layer significantly predicted individual rats' exploratory tendency. Variations in neuronal process volume may explain part of the interindividual variation for cognitive abilities.

Brain G-protein proteolysis by calpain: enhancement by lithium.

Heterotrimeric G-proteins mediate many receptor-coupled signal transduction processes and the cellular concentrations of G-proteins are modulated by several factors, including development, activity, and drugs. The mechanisms causing changes in G-protein concentrations are mostly unknown. The purpose of this study was to determine if G-proteins could be proteolyzed by calpain, a calcium-activated neutral protease that has been linked with neuronal plasticity.

Monoclonal antibodies to glioma-derived growth factor(s).

Several monoclonal antibodies (mAb) reactive against a high-molecular-weight growth factor from human glioblastoma cell lines have been produced by immunizing mice with partially purified preparations from conditioned media. Antibody-secreting colonies were selected by their capacity to bind 35S-labeled glioma cell protein and by reactivity in indirect enzyme-linked immunoadsorbent assay (ELISA), using high-molecular-weight gel filtration fractions and preparative isoelectric focusing fractions containing growth factor activities. Two of the select mAbs (20F3 and 12A12) depleted mitogenic activity (> 50% inhibition, p < 0.

Agonist-induced, GTP-dependent phosphoinositide hydrolysis in postmortem human brain membranes.

Membranes prepared from postmortem human brain were used to measure the activities of three components of the phosphoinositide second messenger system. [3H]Phosphatidylinositol ([3H]PI) hydrolysis was stimulated by directly activating phospholipase C with calcium, by activating guanine nucleotide-binding proteins (G proteins) with guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) or with AIF4, and by receptors activated with several agonists (in the presence of GTP gamma S), including (in order of increasing magnitudes of responses) carbachol, pilocarpine, histamine, trans-1-aminocyclopentyl-1,3-dicarboxylic acid (a selective excitatory amino acid metabotropic receptor agonist), serotonin, and ATP. Gq/11 was identified as the G protein most likely to mediate [3H]PI hydrolysis in human brain membranes based on the findings that this process was not impaired by pretreatment with pertussis toxin and it was inhibited by antibodies specific for the alpha-subunit of Gq/11 but not by antibodies for G0 or Gi1.

Koelliker on Cajal: translated excerpts from Erinnerungen aus meinem Leben.

Albert Koelliker was the foremost histologist of the late 1800s. Koelliker personally worked on many of the same issues as Santiago Ramón y Cajal and was well placed to provide a contemporary commentary on the reception of Cajal's ideas. We have translated selected excerpts from Koelliker's autobiography, Erinnerungen aus meinem Leben, which discuss the ideas of Cajal which were treated no differently than most present day hypotheses; they were disputed on logical, technical, and personal grounds.