Structural variation among major histocompatibility complex class-II genes which predispose to autoimmunity.
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Twenty-four male mice, belonging to 8 different inbred strains, were tested in an 8-arm radial maze. Clear strain differences were found for performance on the third day of training, which correlated very strongly with the size of the hippocampal intra- and infrapy ramidal mossy fibre (iip-MF) terminal fields. These results, combined with those from earlier experiments, indicate that genetic variations of the iip-MF projection influence processes that determine behavioural abilities of mice.
Helical-twist, roll and torsion-angle variations calculated by the Calladine (1982)-Dickerson (1983) rules were scanned along several nucleotide sequences for which DNAase I cleavage data are available. It has been shown that for short synthetic oligomers DNAase I cuts preferentially at positions of high helical twist (Dickerson & Drew, 1981; Lomonossoff et al., 1981). Our calculations indicate that DNAase I sensitive and hypersensitive sites in chromatin are correlated with regions of successive, large, helical-twist angle variations from regular B-DNA. In many cases these regions exhibit large variations in base-pair roll and backbone torsion angles as well. It has been suggested that DNAase I cuts in the vicinity of cruciforms. However, it was recently demonstrated by Courey & Wang (1983) and Gellert et al. (1983) that such cruciform formation in a negatively supercoiled DNA is kinetically forbidden under physiological conditions. We thus propose that clustering of large twist-angle (and/or roll and backbone torsion angle) variations may be among the conformational features recognized by the enzyme. Specific cuts can then preferentially occur at base-pair steps with high helical twists.
The influenza virus A/turkey/Oregon/71 (H7N3) has been adapted to grow in MDCK or chicken embryo cells (CEC) in the absence of trypsin. Changes occurred in the biological properties of the virus variants selected, depending on the cell type used for adaptation. They coincided with enhanced hemagglutinin (HA) activation by intracellular proteolytic cleavage. In the case of MDCK cell selected variants growth, plaque formation, and HA cleavability were restricted to this cell type, whereas the CEC-derived variants displayed altered activities in a broad range of host cells. Unlike the wild-type virus and its MDCK cell-derived variants, CEC variants had acquired pathogenic properties for chickens. By nucleotide sequence analysis of the HA genes of the MDCK cell variants several point mutations were found, which were localized predominantly at the distal, globular part of the HA molecule. The mechanism by which these point mutations increased HA cleavability has not been defined. In the CEC-derived variants besides point mutations, an insertion of 54 nucleotides adjacent to the cleavage site was observed, which corresponds in its sequence to a region in the 28 S ribosomal RNA. This insertion is probably responsible for the altered cleavability of the CEC variants' HA, leading to increased growth potential and pathogenicity.
La Crosse (LAC) virions exposed to different pHs (7.3, 6.2, and 5.4) and temperatures (37 degrees, 20 degrees, and 4 degrees) were preserved in thin layers of vitreous ice and observed by electron cryomicroscopy. Our results indicate that, at lower pH, virus particles interact with each other to form aggregates. In some cases, particles could be interpreted to have fused together. At neutral pH and higher temperatures morphological changes consistent with deformation in some particles were observed. We suggest that low pH conditions are sufficient for membrane fusion events to occur with LAC virions.
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We have isolated a gene encoding one of the 19,000 dalton zein proteins from a maize genomic library constructed in Charon 4A. This gene occurs on a 7.7 kb Eco RI fragment, and based on Southern hybridization analysis, represents one of several homologous sequences present in the maize genome. The nucleotide sequence of the gene predicts a protein composed of 235 amino acids, including a signal peptide of 21 amino acids. There are no intervening sequences in the gene. By comparing the nucleotide sequence of this gene with that of a homologous cDNA clone, we have identified a basis for microheterogeneity within the gene family. The 5' nucleotide sequences of the genomic and cDNA clones are identical, but they differ in the center of the protein, where repeated amino acid sequences occur. A nucleotide sequence encoding a conserved peptide of 20 amino acids is repeated nine times in the center of both of these clones.
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Large, but non-pathological, individual differences in neuroanatomy of the brain exist in rodents, which have been shown to covary with behavioral traits. In the present review, we explore the relationship between variations in the extent of the intra- and infrapyramidal mossy fiber projection of the hippocampus and spatial and non-spatial learning capacities in mice and rats. Preliminary data concerning anatomical variation in the septo-hippocampal cholinergic system and its consequences for individual behavior are also presented. We conclude that the hippocampal intra- and infrapyramidal mossy fiber projection is intimately involved in the regulation of spatial, but not of non-spatial learning capabilities. Although lesion studies have shown that a well-functioning cholinergic system is a prerequisite for performance in spatial learning tasks, our preliminary data suggest that individual differences in the cholinergic system do not explain individual differences in learning.
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The observed propeller twist in base-pairs of crystalline double-helical DNA oligomers improves the stacking overlap along each individual helix strand. But, as proposed by Calladine, it also leads to clash or steric hindrance between purines at adjacent base-pairs on opposite strands of the helix. This clash can be relieved by: (1) decreasing the local helix twist angle between base-pairs; (2) opening up the roll angle between base-pairs on the side on which the clash occurs; (3) separating purines by sliding base-pairs along their long axes so that the purines are partially pulled out of the stack (leading to equal but opposite alterations in main-chain torsion angle delta at the two ends of the base-pair); and (4) flattening the propeller twist of the offending base-pairs. Simple sum functions, sigma 1 through sigma 4, are defined, by which the expected local variation in helix twist, base roll angle, torsion angle delta and propeller twist may be calculated from base sequence. All four functions are quite successful in predicting the behavior of B DNA. Only the helix twist and base roll functions are applicable to A DNA, and the helix twist function begins to fail for an A helical RNA/DNA hybrid. Within these limits, the sequence-derived sum functions match the observed helix parameter variation quite closely, with correlation coefficients greater than 0.900 in nearly all cases. Implications of this sequence-derived helix parameter variation for repressor-operator interactions are considered.
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Our previous work provided evidence that hippocampal opioid peptides form an important neurochemical substrate underlying the gene-dependent exploratory behavior of mice. A prominent hippocampal opioid is dynorphin B, which resides in the mossy fibers exclusively. In order to seek support for causal relationships between dynorphinergic hippocampal mechanisms and exploration, a quantitative-genetic method was chosen. For this purpose, mice from the inbred strains C57BL/6, DBA/2, BLN, and CPB-K were used. Their hippocampal mossy fiber projections were visualized by means of immunohistochemistry, using a highly specific anti-dynorphin B antiserum. The additive-genetic correlations that were estimated suggest pleiotropic gene effects on locomotion, rearing-up, wall-leaning, and several intra- and infrapyramidal mossy fiber (iipMF) variables. Long iipMF, in particular, were found to be associated with high exploratory activity.
On the basis of results from lesion studies in rodents, covariations are expected to exist between naturally-occurring heritable variations in hippocampal morphology and exploratory behavior elicited by novel surroundings. For this reason, we set up a full diallel cross between five inbred mouse strains and analyzed the behavioral and the hippocampal anatomical variation in male animals from this cross. Employing a bivariate extension of the diallel-cross analysis, estimates were obtained for the phenotypical, environmental, and genetical correlations between the phenotypes studied. A factor analysis performed on the matrix of additive-genetic correlations revealed that variations in the size of the intra- and infrapyramidal mossy fiber terminal fields (iip-MF) are negatively related to open-field exploration and novelty-induced fear. These results indicate that having larger iip-MF projections promotes the collection and processing of information about a novel environment, entailing lower levels of exploration and fear.