Repeated injection of MK801: An animal model of schizophrenia?

Glutamate-induced neurotoxicity plays an important role in neurological and psychiatric diseases. Thus, much attention has been given to the potential neuroprotective role of glutamate receptor antagonists, especially to those acting on the N-methyl-d-aspartate (NMDA) subtype. However, in addition to their neuroprotective potential, these compounds have also neurotoxic and psychotogenic properties. In the present study we used repeated injections of MK801 to examine if this non-competitive NMDA receptor antagonist could be used to produce schizophrenia-like alterations in behavior and brain metabolism in animals. Rats were given injections of MK801 (0.1 mg/kg) on six consecutive days, the last dose together with [1-(13)C]glucose and [1,2-(13)C]acetate, to probe neuronal and astrocytic metabolism, respectively. Analyses of extracts from parts of the frontal cortex plus cingulate and retrosplenial cortices and temporal lobes were performed using (13)C and (1)H magnetic resonance spectroscopy. Changes in glutamate and glutamine were restricted to the temporal lobe, in which amounts and labeling from [1-(13)C]glucose and [1,2-(13)C]acetate were increased compared to control. Locomotor activity was slightly higher in rats treated with MK801 compared to untreated animals. Metabolic changes did not resemble the alterations occurring in schizophrenia and those after repeated high dose (0.5 mg/kg) [Kondziella, D., Brenner, E., Eyjolfsson, E.M., Markinhuhta, K.R., Carlsson, M., Sonnewald, U., 2005. Glial-neuronal interactions are impaired in the schizophrenia model of repeated MK801 exposure. Neuropsychopharmacology, Epub ahead of print] but rather those caused by MK801 seen after a single high dose (0.5 mg/kg) [Brenner, E., Kondziella, D., Haberg, A., Sonnewald, U., 2005. Impaired glutamine metabolism in NMDA receptor hypofunction induced by MK801. J. Neurochem. 94, 1594-1603.].     

Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens

Group 1 CD1 molecules have been shown to present lipid and glycolipid Ags of mycobacteria to human T cells. However, a suitable animal model for the investigation of this component of antimycobacterial immunity has not yet been established. Previously, we found that guinea pigs express multiple isoforms of group 1 CD1 proteins that are homologous to human CD1b and CD1c. In this study, we show that CD1-restricted T cell responses can be generated in guinea pigs following immunization with lipid Ags from Mycobacterium tuberculosis. Splenic T cells from lipid Ag-immunized guinea pigs showed strong proliferative responses to total lipid Ags and partially purified glycolipid fractions from M. tuberculosis. These lipid Ag-reactive T cells were enriched in CD4-negative T cell fractions and showed cytotoxic activity against CD1-expressing guinea pig bone marrow-derived dendritic cells pulsed with M. tuberculosis lipid Ags. Using guinea pig cell lines transfected with individual CD1 isoforms as target cells in cytotoxic T cell assays, we found that guinea pig CD1b and CD1c molecules presented M. tuberculosis glycolipid Ags to T cells raised by mycobacterial lipid immunization. These results were confirmed using a T cell line derived from M. tuberculosis lipid Ag-immunized guinea pigs, which also showed CD1-restricted responses and cytolytic activity. Our results demonstrate that CD1-restricted responses against microbial glycolipid Ags can be generated in vivo by specific immunization and provide support for the use of the guinea pig as a relevant small animal model for the study of CD1-restricted immune responses to mycobacterial pathogens.     

Measurements of protein sequence-structure correlations

Correlations between protein structures and amino acid sequences are widely used for protein structure prediction. For example, secondary structure predictors generally use correlations between a secondary structure sequence and corresponding primary structure sequence, whereas threading algorithms and similar tertiary structure predictors typically incorporate interresidue contact potentials. To investigate the relative importance of these sequence-structure interactions, we measured the mutual information among the primary structure, secondary structure and side-chain surface exposure, both for adjacent residues along the amino acid sequence and for tertiary structure contacts between residues distantly separated along the backbone. We found that local interactions along the amino acid chain are far more important than non-local contacts and that correlations between proximate amino acids are essentially uninformative. This suggests that knowledge-based contact potentials may be less important for structure predication than is generally believed.     

Effect of fatty acids of ω6 series on the biosynthesis of arachidonic acid in HTC cells

Summary The influence of the preincubation of HTC cells with fatty acids of 6 series and columbinic acid (St, 9c, 12c 18:3) on the biosynthesis of arachidonic acid was studied. The cells were incubated on a chemically defined medium with or without the addition of unlabeled linoleic, -linolenic, eicosatrienoic, arachidonic, docosatetraenoic, docosapentaenoic and columbinic acids. After 24 hr of preincubation in the presence of the aforementioned fatty acids, [1-¹⁴C]eicosa-8,11,14-trienoic acid was added to the culture medium as the only lipidic source. Twenty-four hours later the synthesis of arachidonic acid and the fatty acid composition of the cells were determined. At 20 MM concentration the 6 fatty acids studied except docosapentaenoic acid produced an increase on the biosynthesis of arachidonic acid compared to the cells incubated in the absence of unlabeled fatty acids in the medium. The fatty acids added to the culture medium were incorporated into the cells and modified their fatty acid composition. Columbinic acid, with a similar structure to linoleic acid, also produced a significant increase on the conversion of eicosatrienoic acid to arachidonic acid. These results would suggest that the effect of both, linoleic and columbinic acids, may be adscribed to their configuration and not necessarily to their transformation in higher homologs, since columbinic acid is unable to be desaturated.All authors are members of the Carrera del Investigador Cientifico of the Consejo Nacional de Investigaciones Cientifícas y Técnicas, Argentina.     

Mutants affecting paramyosin in Caenorhabditis elegans

Four mutants of Caenorhabditis elegans with abnormal muscle structure are described which are alleles of a single locus unc-15. In one of the mutants, E1214, paramyosin is completely absent from both body-wall and pharyngeal musculature. In the other three mutants paramyosin is present but does not assemble into thick filaments. Instead paramyosin paracrystals are formed in the body-wall muscle cells. Myosin filaments lacking paramyosin cores are present in all four mutants, but these filaments fail to integrate stably into the myofilament lattice. One mutant is temperature-sensitive; all four are semi-dominant in their effect on muscle structure. The hypothesis that unc-15 is the structural gene for paramyosin is discussed.     

The dual-targeted RNA editing factor AEF1 is universally conserved among angiosperms and reveals only minor adaptations upon loss of its chloroplast or its mitochondrial target

Plant Molecular Biology - Upon loss of either its chloroplast or mitochondrial target, a uniquely dual-targeted factor for C-to-U RNA editing in angiosperms reveals low evidence for improved...     

Is Mislocalization during Saccades Related to the Position of the Saccade Target within the Image or to the Gaze Position at the End of the Saccade?

A stimulus that is flashed around the time of a saccade tends to be mislocalized in the direction of the saccade target. Our question is whether the mislocalization is related to the position of the saccade target within the image or to the gaze position at the end of the saccade. We separated the two with a visual illusion that influences the perceived distance to the target of the saccade and thus saccade endpoint without affecting the perceived position of the saccade target within the image. We asked participants to make horizontal saccades from the left to the right end of the shaft of a Müller-Lyer figure. Around the time of the saccade, we flashed a bar at one of five possible positions and asked participants to indicate its location by touching the screen. As expected, participants made shorter saccades along the fins-in (<–>) configuration than along the fins-out (>–<) configuration of the figure. The illusion also influenced the mislocalization pattern during saccades, with flashes presented with the fins-out configuration being perceived beyond flashes presented with the fins-in configuration. The difference between the patterns of mislocalization for bars flashed during the saccade for the two configurations corresponded quantitatively with a prediction based on compression towards the saccade endpoint considering the magnitude of the effect of the illusion on saccade amplitude. We conclude that mislocalization is related to the eye position at the end of the saccade, rather than to the position of the saccade target within the image.