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A genetic-correlational study of hippocampal structural variation and variation in exploratory activities of mice.

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.

Animals↗

A genetic-correlational study of hippocampal neurochemical variation and variation in exploratory activities of mice.

Previously, we have demonstrated that hippocampal mossy fibers, containing the opioid peptide dynorphin B, are functionally connected with the gene-dependent exploratory behavior of mice. In order to seek further evidence of causal relationships between dynorphin B action 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. By means of radioimmunoassay, the hippocampal level of dynorphin B was monitored in mice that had been exposed to environmental novelty, as compared to naive animals. Clear evidence was obtained that novelty induces the release of hippocampal dynorphin B. Furthermore, low tissue content was found to be causally connected with high exploratory scores.

Animals↗

Frequency variations of discrete cranial traits in major human populations. IV. Vessel and nerve related variations.

This concludes a series of descriptive statistical reports on discrete cranial traits in 81 human populations from around the world. Four variants classified as vessel and nerve related characters were investigated: patent condylar canal, supraorbital foramen; accessory infraorbital foramen; and accessory mental foramen. A significant asymmetric occurrence without any side preference was detected for the accessory mental foramen. Significant intertrait associations were found between the accessory infraorbital and supraorbital foramina in the panPacific region and Subsaharan African samples. The intertrait associations between the accessory infraorbital foramen and some traits classified as hypostotic were found mainly in the samples from the western part of the Old World, and those as hyperostotic traits in the samples from eastern Asian and the related population samples. With a few exceptions. the occurrence of a patent condylar canal and a supraorbital foramen was predominant in females, but the accessory infraorbital and accessory mental foramina were predominant in males. The frequency distributions of the traits showed interregional clinality and intraregional discontinuity. A temporal trend was found in the Northeast Asian region in the frequencies of the accessory infraorbital and accessory mental foramina. The diversity of modern human discrete cranial traits may at least in part be attributable to differential retention or intensification from an ancestral pattern.

Blood Vessels↗

V3 seroreactivity and sequence variation: tracking the emergence of V3 genotypic variation in HIV-1-infected patients.

OBJECTIVE: To investigate the relationship between V3-specific immune responses and viral quasispecies evolution in 10 HIV-1-seropositive patients enrolled in a phase I trial of recombinant gp160. METHODS: Serologic responses to the HIVLAI V3 loop and autologous V3 loop DNA sequences were sequentially determined over a 3-4-year interval. RESULTS: Six patients either seroconverted or had a > or = 42-fold boost in titer to the V3 reagent associated with an average of 3.2 amino-acid changes in their autologous V3 loops. Four patients with < or = 11-fold change in titer to the V3 loop showed an average of 0.75 amino-acid changes. Attempts to measure autologous V3 loop responses in four patients using a peptide enzyme-linked immunosorbent assay technique did not show a distinct binding preference for autologous versus heterologous V3 loop peptides. Thus, we interpret seroreactivity to the heterologous HIVLAI V3 loop to reflect the broadness of the V3 immune response rather than a direct measure of epitope-specific immune pressure. CONCLUSIONS: These data suggest that the broadness of serologic responses to viral epitopes are reflected in the rate of evolution of their cognate coding sequences and support the view that the immune response to HIV-1 results in the continuous selection of new viral variants during the course of disease.

AIDS Vaccines↗

pMGA phenotypic variation in Mycoplasma gallisepticum occurs in vivo and is mediated by trinucleotide repeat length variation.

Chickens were infected with a pathogenic strain of Mycoplasma gallisepticum, and the expression of pMGA, the major surface protein, was inferred by examination of colonies from ex vivo cells. Within 2 days postinfection, 40% of cells had ceased the expression of the original pMGA surface protein (pMGA1.1), and by day 6, the majority of recovered cells were in this category. The switch in pMGA phenotype which had occurred in vivo was reversible, since most colonies produced from ex vivo progenitors exhibited frequent pMGA1. 1(+) sectors. After prolonged in vivo habitation, increasing proportions of recovered cells gave rise to variant pMGA colonies which had switched from the expression of pMGA1.1 to another gene, pMGA1.2, concomitant with the acquisition of a (GAA)(12) motif 5' to its promoter. Collectively, the results suggest that changes in M. gallisepticum pMGA gene expression in vivo are normal, common, and possibly obligate events for successful colonization of the host. Surprisingly, the initial cessation of pMGA1.1 expression occurred in the absence of detectable pMGA antibodies and seemed to precede the adaptive immune response.

Animals↗

Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation.

INTRODUCTION: Interpretation of results from mutation screening of tumour suppressor genes known to harbour high risk susceptibility mutations, such as APC, BRCA1, BRCA2, MLH1, MSH2, TP53, and PTEN, is becoming an increasingly important part of clinical practice. Interpretation of truncating mutations, gene rearrangements, and obvious splice junction mutations, is generally straightforward. However, classification of missense variants often presents a difficult problem. From a series of 20,000 full sequence tests of BRCA1 carried out at Myriad Genetic Laboratories, a total of 314 different missense changes and eight in-frame deletions were observed. Before this study, only 21 of these missense changes were classified as deleterious or suspected deleterious and 14 as neutral or of little clinical significance. METHODS: We have used a combination of a multiple sequence alignment of orthologous BRCA1 sequences and a measure of the chemical difference between the amino acids present at individual residues in the sequence alignment to classify missense variants and in-frame deletions detected during mutation screening of BRCA1. RESULTS: In the present analysis we were able to classify an additional 50 missense variants and two in-frame deletions as probably deleterious and 92 missense variants as probably neutral. Thus we have tentatively classified about 50% of the unclassified missense variants observed during clinical testing of BRCA1. DISCUSSION: An internal test of the analysis is consistent with our classification of the variants designated probably deleterious; however, we must stress that this classification is tentative and does not have sufficient independent confirmation to serve as a clinically applicable stand alone method.

Amino Acid Sequence↗

Genetic variation in packed cell volume associated with variations in response to cold temperature.

The heritability of packed red blood cell volume (PCV) and its correlation to gain in chicks brooded at a relatively cold (26.7 C) and a normal (32.2 C) environmental temperature were compared. The PCV of progeny from 28 sire families brooded at 26.7 C was 32.7% compared to 30.9% for progeny from the same sire families brooded at 32.2 C. The respective PCV heritabilities for the 26.7 C and 32.2 C groups were .51 and .57. There were no significant differences in gain for the groups brooded at different temperatures, and PCV was not correlated with gain.U

Adaptation, Physiological↗

[Individual variation in the frequency of chromosome aberrations under the influence of chemical mutagens. I. Inter-cultural and inter-individual variations in the effect of mutagens on human lymphocytes].

The study of the distribution law of human peripheral blood cultures for the sensitivity to thiophosphamide was performed. In the first experiment the blood from one person was used, in the second one the blood was used from different persons. "The percent of aberrant cells" and "the number of chromosome breaks per 100 cells" were scored. The distribution law of the cultures in all the experiments was found to be normal. Analysis of the variances on the percent of aberrant cells showed that the distribution law of the cultures received from one donor corresponded to the binomial one, and that of the cultures received from different donors--to the Poisson's one.

Alkylating Agents↗