Equilibrium frequencies of α-globin genes

A mathematical model has been developed to study the mechanism of the maintenance of variable numbers of α-globin genes in human populations. The model incorporates both selection and unequal crossing-over. The selection is formulated so that a homozygous individual with a double deletion is lethal and a heterozygous individual with a deletion or addition of an α-globin gene in a chromosome has decreased fitness. This differs from the previous models of stabilizing selection studied by Ohta (1981) and Takahata (1981). The effect of random genetic drift on the α-thalassemia polymorphims has also been studied.It has been shown that, although the results obtained are compatible with the observation of the low frequency of triple α-globin loci, it cannot explain the high frequency of single and double deletions in Asian populations. For the latter case, some type of heterozygote advantage may be operating.     

Flowering and Endogenous Levels of Benzoic Acid in Lemna Species

The occurrence of benzoic acid, a flower-inducing factor inLemna species, in L. paucicostata strains 151, 381, 321 andL. gibba G3 was established by several purification steps andfinal use of gas liquid chromatography-selected ion monitoring.Quantitative analyses of benzoic acid were made in non-floweringand flowering Lemna to determine differences in levels. Theendogenous level of benzoic acid was shown to vary dependingon culture conditions, but no positive correlation could befound between the endogenous level of benzoic acid and floweringof Lemna. (Received October 6, 1982; Accepted December 23, 1982)     

Molecular evolution and phylogeny of the human AIDS viruses LAV,HTLV-III,and ARV

Summary A phylogenetic tree for the human lymphadenopathy-associated virus (LAV), the human T-cell lymphotrophic virus type III (HTLV-III), and the acquired immune deficiency syndrome (AIDS)-associated retrovirus (ARV) has been constructed from comparisons of the amino acid sequences of their gag proteins. A method is proposed for estimating the divergence times among these AIDS viruses and the rates of nucleotide substitution for their RNA genomes. The analysis indicates that the LAV and HTLV-III strains diverged from one another after 1977 and that their common ancestor diverged from the ARV virus no more than 10 years earlier. Hence, the evolutionary diversity among strains of the AIDS viruses apparently has been generated within the last 20 years. It is estimated that the genome of the AIDS virus has a nucleotide substitution rate on the order of 10^–3 per site per year, with the rate in the second half of the genome being double that in the first half.     

Mechanism of O2- generation in reduction and oxidation cycle of ubiquinones in a model of mitochondrial electron transport systems

O2- generation in mitochondrial electron transport systems, especially the NADPH-coenzyme Q10 oxidoreductase system, was examined using a model system, NADPH-coenzyme Q1-NADPH-dependent cytochrome P-450 reductase. One electron reduction of coenzyme Q1 produces coenzyme Q1-. and O2- during enzyme-catalyzed reduction and O2+ coenzyme Q1-. are in equilibrium with O2- + coenzyme Q1 in the presence of enough O2. The coenzyme Q1-. produced can be completely eliminated by superoxide dismutase, identical to bound coenzyme Q10 radical produced in a succinate/fumarate couple-KCN-submitochondrial system in the presence of O2. Superoxide dismutase promotes electron transfer from reduced enzyme to coenzyme Q1 by the rapid dismutation of O2- generated, thereby preventing the reduction of coenzyme Q1 by O2-. The enzymatic reduction of coenzyme Q1 to coenzyme Q1H2 via coenzyme Q1-. is smoothly achieved under anaerobic conditions. The rate of coenzyme Q1H2 autoxidation is extremely slow, i.e., second-order constant for [O2][coenzyme Q1H2] = 1.5 M-1.s-1 at 258 microM O2, pH 7.5 and 25 degrees C.     

Properties of a coenzyme, pyrroloquinoline quinone: generation of an active oxygen species during a reduction-oxidation cycle in the presence of NAD(P)H and O2

The oxidation of NAD(P)H by pyrroloquinoline quinone (PQQ) was non-enzymatically carried out at physiological pH in the presence of O2. The PQQ-NAD(P)H system requires about 1 mol of O2 for the oxidation of 1 mol of NAD(P)H. The oxidation of NAD(P)H occurred at a pseudo-first-order rate with respect to NAD(P)H and was of zero order with respect to PQQ concentration in in the presence of O2: k0[PQQ] [NAD(P)H] = k1 [NAD(P)H], where k0[PQQ] = k1, in which [PQQ] represents the initial concentration of PQQ. k0 values for NADH and NADPH were 3.4.10(2) M-1.min-1 and 2.0.10(2) M-1.min-1, respectively, at 25 degrees C and at 258 microM O2 (initial concentration). The system produced O-2, probably by the interaction of PQQ.H and/or NAD(P).with O2, during the oxidation of NAD(P)H. PQQH2 and PQQ.H were easily oxidized to PQQ in the presence of O2, yielding H2O2.     

DNA diagnosis of hydatidiform mole using the polymerase chain reaction

Summary We have used the polymerase chain reaction (PCR) technique for the diagnosis of hydatidiform mole, a trophoblastic disease. For this, we targeted the hypervariable 3 flanking region of the APOB gene (APOB/ VNTR) because of its high heterozygosity index (0.61) in the Japanese population. We examined seven clinical cases which were tentatively diagnosed as hydatidiform moles. Five of these revealed DNA segments unique to the paternal APOB allele, allowing us to diagnose a complete mole. The PCR technique for targeting the APOB/VNTR appears useful for early diagnosis of hydatidiform mole.     

Effect of age on α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding sites in the rat brain studied by in vitro autoradiography

Receptors for excitatory amino acid,L-glutamate, have been classified into three subtypes named as N-methyl-D-aspartate (NMDA), quisqualate (QA) and kainate receptors. In the present study, an effect of age on binding sites of [³H]-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (³H-AMPA), a QA agonist, was studied in the rat brain through quantitative in vitro autoradiography.³H-AMPA binding sites were most concentrated in the hippocampus and cerebral cortex where glutamate receptors have been demonstrated to play a role in synaptic transmission. In aged rats,³H-AMPA binding sites in the hippocampus and cerebral cortex were not significantly changed. In our previous studies, it was noticed that strychnine-insensitive glycine receptors, which functionally coupled with NMDA receptors, showed marked age-dependent decreases in telencephalic regions. It has been shown that the glutamatergic neuronal system is involved in learning and memory. Nevertheless, it is considered that AMPA binding sites are not involved in the decline of neuronal functions, especially impairment of learning and memory, accompanying with aging process.     

12- and 15-lipoxygenases in rat pineal gland

A whole organ or a homogenate of rat pineal gland was incubated with arachidonic Acid. Two predominant metabolites were identified by mass spectrometry to be 12-hydroxy-5,8,10,14-eicosatetraenoic acid and 10-hydroxy-11,,12-epoxy-5,8,14-eiconsatrienoic acid. 15-Hydroxy-5,8,11,13-eicosatetraenoic acid was also formed in a smaller amount. In addition, peroxy acids appeared rapidly only at the initial state of reaction. In various parts of rat brain the 12-lipoxygenase activity was by far the highest in pineal gland, and less than 5% of the activity was found in pituitary gland and hypothalamus.