Genealogy of Principal Strains of the Yeast Genetic Stock Center

We have constructed a genealogy of strain S288C, from which many of the mutant and segregant strains currently used in studies on the genetics and molecular biology of Saccharomyces cerevisiae have been derived. We have determined that its six progenitor strains were EM93, EM126, NRRL YB-210 and the three baking strains Yeast Foam, FLD and LK. We have estimated that approximately 88% of the gene pool of S288C is contributed by strain EM93. The principal ancestral genotypes were those of segregant strains EM93-1C and EM93-3B, initially distributed by C. C. Lindegren to several laboratories. We have analyzed an isolate of a lyophilized culture of strain EM93 and determined its genotype as MATa/MATα SUC2/SUC2 GAL2/gal2 MAL/MAL mel/mel CUP1/cup1 FLO1/flo1. Strain EM93 is therefore the probable origin of genes SUC2, gal2, CUP1 and flo1 of S288C. We give details of the current availability of several of the progenitor strains and propose that this genealogy should be of assistance in elucidating the origins of several types of genetic and molecular heterogeneities in Saccharomyces.     

Novel silylated steroids as aromatase inhibitors

Androst-4-en-3-one analogs incorporating a trimethylsilyl or a trimethylsilylmethyl group at C-1, C-2 or C-19 were prepared and evaluated as inhibitors of aromatase. Only 10-[1-hydroxy-2-(trimethylsilyl)ethyl]estr-4-ene-3,17-dione inhibited human placental aromatase. Enzyme kinetic analysis revealed competitive inhibition [apparent dissociation constant (Ki) of 562 +/- 12 nM] associated with marginal time-dependent inhibition.     

Endogenous opioids modulate fetal rabbit lung maturation

To test the hypothesis that endogenous opioids modulate fetal lung development, separate groups of pregnant rabbits received daily injections of saline, morphine (1 mg/kg body wt), or the opioid antagonist naloxone (0.4 and 5.0 mg) for 10 days during their last trimester of pregnancy. The corresponding groups of fetuses were then delivered prematurely on day 28 of gestation (term approximately 31 days) and evaluated with respect to differences in body weight, lung weight, and the ratios of wet to dry lung weight and lung dry weight to body weight, the static inflation and deflation air and saline pressure-volume (P-V) characteristics of the lungs, and lung morphology. Mean values for body weight, lung weight, and the ratios of lung wet to dry weight and lung dry weight to body weight were not significantly different among the saline control (C), morphine (M)-, and naloxone (NLX)-treated fetuses. On the other hand, the fetal air P-V curves varied significantly (P less than 0.001), wherein the M-treated group depicted increased lung distensibility and alveolar stability on lung deflation, whereas the opposite was obtained in the NLX-treated fetuses. Moreover, morphometric analyses demonstrated that the mean alveolar air space-to-tissue ratio in lungs from M-treated fetuses were significantly greater than that observed either in C or in NLX-treated fetuses (P less than 0.05); however, the air space-to-tissue ratio did not significantly vary between the C and NLX-treated animals. These observations provide new evidence that endogenous opioids enhance fetal lung maturation.     

Nutrient control of brain neurotransmitter synthesis and function

Dietary fluctuations in nutrient availability are factors in the regulation of brain function. Until recently the prevailing view was that brain biochemistry and function were influenced by diet only when biochemical and clinical evidence of nutrient deficiency was present. It is now clear, however, that the brain is sensitive and responsive to diet composition. Preliminary data show that variation in vitamin and mineral nutrient intakes over ranges that are considered to maintain normal nutritional status may impact on brain biochemistry, owing to their many coenzyme roles. Furthermore, the synthesis of at least five brain neurotransmitters, namely serotonin, the catecholamines, acetylcholine, histamine, and glycine responds to dietary fluctuations in availability of their nutrient precursors, tryptophan, tyrosine, choline, histidine, and threonine, respectively. Not only are these biochemical events altered by normal variations in diet composition, but considerable evidence now exists to show that the brain uses this information to regulate many functions. Future studies can be expected to continue to elucidate the links between diet, brain neurotransmission, and brain function, and to exploit the application of these links in understanding the function of the brain under normal and disease conditions.