Relationship of chloroquine-induced redistribution of a neutral aminopeptidase to hemoglobin accumulation in malaria parasites

To study the relationship between neutral aminopeptidase activity and hemoglobin accumulation in malaria parasites, we treated mice infected with Plasmodium berghei NYU-2 with chloroquine intraperitoneally in doses ranging from 0.3 to 3 micromol per 25 g mouse. Preparations of infected erythrocytes (normalized to represent 1000 parasites per 1000 erythrocytes) hydrolyzed 1200 nmol of leucine-p-nitroanilide per minute per milliliter of packed erythrocytes, which was 10x more than that of uninfected preparations. The activity in infected preparations was distinguished by resistance to ferriprotoporphyrin IX and puromycin and susceptibility to inhibition by ethanol and Tris. Chloroquine treatment caused the activity in unwashed membrane ghosts of infected preparations to decrease by 50% despite an increase in total activity. Concomitantly, hemoglobin in washed membrane ghosts increased. Electron microscopy revealed that the hemoglobin was retained in endocytic vesicles. Chloroquine-induced redistribution of a neutral aminopeptidase may be the cause of hemoglobin accumulation in endocytic vesicles of malaria parasites.     

Variation of amino acid properties in all-beta globular and outer membrane protein structures

Discriminating outer membrane (OM) proteins from globular proteins is an important task. The structural analysis of β-strands dominating globular (all-β) proteins and OM proteins provides useful insight to distinguish between them. In this work, we analyze the characteristic features of the 20 amino acid residues in all-β and OM proteins. We set up numerical indices for several properties of amino acid residues, such as, conformational parameters, surrounding hydrophobicity, accessible surface area and reduction in accessibility, and inter-residue contacts. We found that all the aromatic residues prefer to be in β-strands of both globular and OM proteins. The surrounding hydrophobicity of aromatic and non-polar amino acid residues in globular proteins is significantly higher than that of OM proteins. The residues Trp, Arg, Phe and Gln show a remarkable difference of reduction in accessibility between all-β globular (βG) and OM proteins. The positively charged residues, Lys and Arg in the membrane part of OM proteins have more number of contacts than globular proteins. Further, the behavior of the 20 amino acid residues in β-strand segments of globular and OM proteins have been discussed. The parameters developed in this work can be used for identifying transmembrane β-strands in OM proteins and for discriminating βG proteins from OM proteins.     

Variation in sexual size dimorphism among populations: testing the differential‐plasticity hypothesis

Sexual size dimorphism (SSD) is a common phenomenon in animals and varies widely among species and among populations within species. Much of this variation is likely due to variance in selection on females vs. males. However, environmental variables could have different effects on females vs. males, causing variation in dimorphism. In this study, we test the differential‐plasticity hypothesis, stating that sex‐differential plasticity to environmental variables generates among‐population variation in the degree of sexual dimorphism. We examined the effect of temperature (22, 25, 28, and 31 °C) on sexual dimorphism in four populations of the cockroach Eupolyphaga sinensis Walker (Blattaria: Polyphagidae), collected at various latitudes. We found that females were larger than males at all temperatures and the degree of this dimorphism was largest at the highest temperature (31 °C) and smallest at the lowest temperature (22 °C). There is variation in the degree of SSD among populations (sex*population interaction), but differences between the sexes in their plastic responses (sex*temperature interaction) were not observed for body size. Our results indicated that sex‐differential plasticity to temperature was not the cause of differences among populations in the degree of sexual dimorphism in body size.     

Mouse hemoglobin during gestation. Absence of fetal hemoglobin

A "fetal hemoglobin' has been reported to exist during mouse gestation, Investigations using CMC chromatography, starch gel electrophoresis or isoelectric focusing have shown a hemoglobin band from fetal tissues, and blood was obtained which was different from the adult hemoglobin and designated a "fetal hemoglobin'. In the current study isoelectric focusing was used to study the hemoglobins existing in the tissues and blood during fetal and neonatal development and the results suggest there is no "fetal hemoglobin' present during gestation. It appears that the hemoglobin designated as "fetal' in our laboratory was a methemoglobin formed by an incomplete reaction of KCN with the hemoglobin. The additional hemoglobin bands which were obtained from fetal liver or neonatal spleen tissues appeared to be a modified adult hemoglobin.     

Glycosylated hemoglobin and raubasine in experimental streptozotocin diabetes

Streptozotocin (Stz) diabetes was induced to study the changes of glycosylated hemoglobin in rats treated with raubasina (R), drug widely used in the vascular compliance of natural human diabetes. Raubasina reduced significantly the increase of glycosylated hemoglobin found in streptozotocin induced diabetes. These results support data obtained in clinical trials.     

Changes in the peripheral blood, liver and spleen during the long-term experimental administration of modified hemoglobin

The study of chronic toxicity of polymerized hemoglobin solutions (PHb) has demonstrated the relationship between the dose of the solution administered and the level of functional and morphological changes induced in various organs of experimental animals. Lower doses (1.8 g/kg) of PHb had no effect on the values of protein and carbohydrate metabolism, while the high doses (10-15 g/kg) of PHb resulted in the impairment of protein synthesis, morphological changes in the spleen and lymphatic nodes.     

Evolutionary potential: A mathematical hypothesis of mouse hemoglobin beta chain evolution

Summary This paper examines the possibility that the linkage arrangements and regulatory properties of genes may be influenced by selection. A mathematical hypothesis is developed in order to show how selective properties of hemoglobin beta chains could have influenced the linkage and regulation of their structural genes. The hypothesis is applied to the case of mouse hemoglobin beta chains. In most mice, closely-linked pairs of loci (doublets) code for two structurally divergent beta chains in unequal amounts. Some mouse strains have singlet alleles, however, coding for another beta chain variant. With the mathematical hypothesis, one can show that selectively determined evolutionary potentials may have favored changes in proportions of major and minor chains produced by a doublet allele. In the extreme case, zero production of the minor chain may give a selective advantage, leading to a ringlet; conversely, selection may favor linking another gene to the singlet locus to give a doublet. A specific prediction of the model is the stable maintenance under certain conditions of multiple alleles at regulatory loci. The concept of evolutionary potential thus suggests that selection could have influenced the evolution of genotypic fitnesses, in addition to causing changes in gene frequencies as in standard population genetics models.