Mutagenicity of oxaspiro compounds with Salmonella

The spiro attachment of an epoxide group to a tetrahydropyran ring in the trichothecene mycotoxins has prompted this study of the mutagenicity and alkylation rates of the trichothecene, anguidine, and 5 related model oxaspiro compounds. While the model compounds were weak alkylating agents of 4-(4-nitrobenzyl)pyridine as a test nucleophile, anguidine lacks such activity. Also, while mutagenicity was not established for anguidine in Salmonella TA100, 3 of the oxaspiro compounds were weakly mutagenic and 2 compounds were toxic to the bacteria. The toxicity and mutagenicity of the model compounds are more related to their polarity than to their alkylation rates.     

Bias of heritability estimates from twin data in presence of errors of zygosity determination

Simple heritability estimators of continuous as well as discrete traits from twin data are known to overestimate the degree of genetic determination of the measured traits for several reasons. Errors of zygosity determination will, however, underestimate the true heritability. The bias due to wrong assignment of dizygous twin pairs into monozygous type is evaluated here, and the results indicate that this negative bias has a compensatory effect on the estimate of the degree of genetic determination when other factors of similarity between twin pairs are taken into account. It is shown that when an estimate of zygosity error is available, the bias due to this factor can be evaluated quantitatively, and hence the adjustment for zygosity error can be incorporated in the estimation of the degree of genetic determination of a trait. Although this theory is explicitly developed here for twin studies, the general principle also applies for other types of errors of determining the degree of biological relationships for estimation of heritability, in which case this type of error may be more important than the simple zygosity error.     

Mutagenicity of aromatic glycidyl ethers with Salmonella

6 aromatic glycidyl ethers containing naphthyl, biphenyl or benzylphenyl substituents were synthesized. These epoxides together with the commercially available compounds 2-biphenylyl glycidyl ether were examined for dose-mutagenicity relationships using the plate incorporation Ames test with Salmonella typhimurium strains TA100 and TA1535. Structure-mutagenicity relationships were further examined for these compounds and 3 phenyl glycidyl ethers by concurrent testing at a single dose with strain TA100. Meaningful correlations could not be established for the mutagenicity of these epoxides to their molecular volumes, partition values, nor to their reactivities with the model nucleophile, 4-(4-nitrobenzyl) pyridine. However, it was noted that increased conjugated aromatic unsaturation with its resulting planarity led to increased mutagenicity and that this effect decreased when it was further removed from the epoxide moiety.     

Heterozygote deficiency,population substructure and their implications in DNA fingerprinting

Summary Substructured populations exhibit an overall deficiency of heterozygosity whose proportional magnitude depends on the nature of substructuring, i.e., the number of subpopulations (s), their time of divergence (t) from the ancestral population, and the rate of gene flow amongst them (m). Since apparent heterozygote deficiency could be caused by many factors other than population substructuring, one must examine the nature of substructuring that could produce the observed extent of heterozygote deficiency, in order to infer the substructuring from an observed heterozygote deficiency. Using the equivalence of proportional heterozygote deficiency and the coefficient of gene differentiation (G _ST), we can generate isolines of G _ST as functions of s, t (in units of 2N _e generations, N _e being the effective population size) and m. Analytical results suggest that large G _ST values cannot be reached by substructuring alone, unless the number of subpopulations are large and they remain isolated over a long period of time. Application of the theory to population data on six variable number of tandem repeats (VNTR) loci in US Caucasians and US Blacks demonstrates that the observed heterozygote deficiencies at these loci cannot be explained by substructuring within these populations alone. This is so because such large values of G _ST (3%–10%) would require an absence of gene exchange between the subpopulations and a divergence time from each other of at least 25000 years ago, neither of which is compatible with the demography and ethnohistory of US Caucasians and Blacks. In contrast, the inability to detect extreme-sized alleles and/or incomplete resolution of nearly similar-sized alleles following Southern gel electrophoresis could easily explain the observed heterozygote deficiencies. The implications of these results are discussed in the context of the forensic use of DNA-typing data, and justify the employment of population genetic principles in forensic genetics.     

Comparison of five tandem repeat loci between humans and chimpanzees.

Five tandem repeat loci were studied in humans and chimpanzees using VNTR probes derived from human DNA. Shared alleles were found at three loci and were often the modal allele in one species but never in both. There was no difference in the mean number of alleles per locus. However, these species exhibited substantially different levels of gene diversity, with chimpanzees monomorphic at two loci. Evidence of reduced variability in chimpanzees corroborates earlier comparisons using isozymes and plasma proteins. Molecular mechanisms, population dynamics, or both may be responsible for these differences. Equal numbers of alleles per locus may reflect high mutation rates. By one test, chimpanzees were out of equilibrium at one locus, which may reflect a typing error or population substructure. The long divergence time, and the high probability of backward mutations, precludes accurate estimation of genetic distance between these species.     

Effect of Erythropoietin on the interaction of Concanavalin A with rat erythrocytes

Effect of Erythropoietin (Ep) on the interaction of Concanavalin A (Con A) with rat erythrocytes was studied using ¹²⁵I-labelled Con A. Binding of Con A to erythrocytes was dependent on time and cell concentration. Starvation caused an elevation of the lectin binding capacity of red cells which again came down towards the normal level on Ep administration to starved rats. Binding of Con A to erythrocytes decreased linearly with increasing concentration of Ep. Specificity of binding was confirmed by inhibition studies with -methyl-D-mannopyranoside (Me Man) Cells from the starved rats compared to those from normal and Ep treated animals were less prone to inhibition by this sugar analog. Positive cooperative binding of Con A to rat erythrocyte was observed at low concentration of Con A but was absent at higher lectin concentrations. Starvation caused an increase in the number of binding sites per cell which returned to normal level after Ep treatment. Under identical conditions, binding affinities were not much changed in these cells. Cells from the starved animals were more susceptible to agglutination compared to those from normal and Ep-treated rats. Microviscosity and cholesterol/phospholipid ratio of red cell membrane decreased in the starved animals which retraced its way back towards the normal level after Ep treatment.     

Epidermal growth factor binding in rat uterus during the peri-implantation period

The profile of epidermal growth factor (EGF) binding to uterine membranes of rats on Day 1 through Day 7 of pregnancy was studied. The binding was lowest on Day 1 and increased gradually through the pre- and postimplantation periods. Binding affinity of the Day 7 uterine membranes was considerably higher than that of the Day 1. Apparent affinity constants (Ka) of Day 1 and Day 7 membranes were 0.29 X 10(-8) M and 1.03 X 10(-8) M respectively. To our knowledge, this is the first report of the modulation of EGF binding to uterine membranes by progesterone-estrogen interaction during early pregnancy.     

Reproductive physiology of the clouded leopard: II. A circannual analysis of adrenal-pituitary-testicular relationships during electroejaculation or after an adrenocorticotropin hormone challenge

A circannual analysis was made of serum cortisol, luteinizing hormone (LH), and testosterone concentrations in the male clouded leopard (Neofelis nebulosa). Group I males (n = 4), maintained in a standardized environment, were bled serially during a regimented anesthesia/electroejaculation episode occurring monthly (beginning in January, ending in December). Additional sampling intervals were conducted under anesthesia only (control, n = 8), anesthesia plus a single adrenocorticotropin hormone challenge (ACTH, Cortrosyn, n = 4), or anesthesia plus a single 25 micrograms injection of gonadotropin-releasing hormone (GnRH, Gonadorelin, n = 4). Group II males (n = 6) from various zoological collections were sampled serially under the same semen collection conditions on one random occasion within the year. Serum cortisol levels were 2 times greater than values measured in comparable studies involving other felid species. Cortisol concentrations were similar during electroejaculation and control (anesthesia only) episodes, and mean levels did not rise as a result of semen collection. Adrenocorticotropin caused an immediate rise in cortisol to levels at least 1.5 times greater than electroejaculated or control counterparts. Mean concentrations of basal cortisol in individual males gradually increased as the year progressed, possibly as a consequence of repeated psychogenic stress. Between seasons, there were no differences in mean LH; however, testosterone levels were greater (p less than 0.05) in the winter compared to all other seasons. There were no differences (p greater than 0.05) between individual males in secretory patterns or mean concentrations of cortisol, LH, or testosterone. Within males, distinct temporal fluctuations were observed in both LH and testosterone during the approximately 80-min sampling interval. Neither LH nor testosterone profiles appeared affected by cortisol patterns during electroejaculation or after an ACTH challenge. A bolus of GnRH induced a marked rise in serum LH and testosterone within 15 and 30 min respectively, indicating that these two hormones were coupled. Both LH and testosterone profiles in Group II males mimicked those in Group I; concentrations of cortisol in Group II males immobilized on one occasion were similar to those of Group I animals sampled from January-May but appeared to be less than values measured from June-December. These data demonstrate that the clouded leopard, compared to other felids, produces markedly elevated concentrations of cortisol, which are likely related to an aggressive behavioral temperament.(ABSTRACT TRUNCATED AT 400 WORDS)