Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein gene

We have analyzed the conserved regions of the gene coding for the circumsporozoite protein (CSP) in 12 species of Plasmodium, the malaria parasite. The closest evolutionary relative of P. falciparum, the agent of malignant human malaria, is P. reichenowi, a chimpanzee parasite. This is consistent with the hypothesis that P. falciparum is an ancient human parasite, associated with humans since the divergence of the hominids from their closest hominoid relatives. Three other human Plasmodium species are each genetically indistinguishable from species parasitic to nonhuman primates; that is, for the DNA sequences included in our analysis, the differences between species are not greater than the differences between strains of the human species. The human P. malariae is indistinguishable from P. brasilianum, and P. vivax is indistinguishable from P. simium; P. brasilianum and P. simium are parasitic to New World monkeys. The human P. vivax-like is indistinguishable from P. simiovale, a parasite of Old World macaques. We conjecture that P. malariae, P. vivax, and P. vivax-like are evolutionarily recent human parasites, the first two at least acquired only within the last several thousand years, and perhaps within the last few hundred years, after the expansion of human populations in South America following the European colonizations. We estimate the rate of evolution of the conserved regions of the CSP gene as 2.46 x 10(-9) per site per year. The divergence between the P. falciparum and P. reichenowi lineages is accordingly dated 8.9 Myr ago. The divergence between the three lineages leading to the human parasites is very ancient, about 100 Myr old between P. malariae and P. vivax (and P. vivax-like) and about 165 Myr old between P. falciparum and the other two.      

喀喇昆仑、昆仑山地区植物元素含量的区域分异和数量分析

对喀喇昆仑、昆仑山地区87种植物21个元素含量及区域分异的研究表明,Ca、Cr、Cd、Fe、V含量比高等植物含量偏高,Ph、P的含量偏低。同种植物在不同地点元素含量有差异。盐柴荒漠植物中Na、K、Mg、P含量较高;高山草甸、冰缘植被植物Ba、Ca、Fe、V、Ti含量较高。各植被类型植物元素含量Na/K差异最大,Ca/Mg较小,Fe/Al差异最小。其变异系数分别为153.5、20.5和15.9.%     

Oligomeric forms of the membrane-bound acetylcholine receptor disclosed upon extraction of the M(r) 43,000 nonreceptor peptide

Oligomeric forms of the acetylcholine receptor are directly visualized by electron microscopy in receptor-rich membranes from torpedo marmorata. The receptor structures are quantitatively correlated with the molecular species so far identified only after detergent solubilization, and further related to the polypeptide composition of the membranes and changes thereof. The structural identification is made possibly by the increased fragility of the membranes after extraction of nonreceptor peptides and their subsequent disruption upon drying onto hydrophilic carbon supports. Receptor particles in native membranes depleted of nonreceptor peptides appear as single units of 7-8 nm, and double and multiple aggregates thereof. Particle doublets having a main-axis diameter of 19 +/- 3 nm predominate in these membranes. Linear aggregates of particles similar to those observed in rotary replicas of quick-frozen fresh electrolytes (Heuser, J.E. and S. R. Salpeter. 1979, J. Cell Biol. 82: 150-173) are also present in the alkaline-extracted membranes. Chemical modifications of the thiol groups shift the distribution of structural species. Dithiothreitol reduction, which renders almost exclusively the 9S, monomeric receptor form, results in the observation of the 7-8 nm particle in isolated form. The proportion of doublets increases in membranes alkylated with N-ethylmaleimide. Treatment with 5,5’-dithiobis-(nitrobenzoic acid) increases the proportion of higher oligomeric species, and particle aggregates (n=oligo) predominate. The nonreceptor v-peptide (doublet of M(r) 43,000) appears to play a role in the receptor monomer-polymer equilibria. Receptor protein and v-peptide co-aggregate upon reduction and reoxidation of native membranes. In membranes protected ab initio with N- ethylmaleimide, only the receptor appears to self-aggregate. The v-peptide cannot be extracted from these alkylated membranes, though it is easily released from normal, subsequently alkylated or reduced membranes. A stabilization of the dimeric species by the nonreceptor v-peptide is suggested by these experiments. Monospecific antibodies against the v-peptide are used in conjunction with rhodamine- labeled anti-bodies in an indirect immunoflourescence assay to map the vectorial exposure of the v-peptide. When intact membranes, v-peptide depleted and “holey” native membranes (treated with 0.3 percent saponin) are compared, maximal labeling is obtained with the latter type of membranes, suggesting a predominantly cytoplasmic exposure of the antigenic determinants of the v-peptide in the membrane. The influence of the v-peptide in the thiol-dependent interconversions of the receptor protein and the putative topography of the peptide are analyzed in the light of the present results.     

Regulation of autoimmune response to mouse thyroglobulin: influence of H-2D-end genes.

Studies were initiated to define the H-2-linked genetic control of response to self-determinants of MTg. In addition to the Ir gene control of H-2K end, a modifying effect of D end was seen. The extent of regulation depended upon the derivation of the K-end Ir-Tg gene(s) as well as the D-end genes. When the Ir-Tg gene was from good responder H-2k and H-Ss strains, and the H-2D-end gene from the d allele, antibody levels were moderate to high but cellular infiltration was significantly reduced. These findings demonstrate genetic interaction between I-region and D-end gene products in the response to a self-antigen, MTg.     

Genetic control of the primary humoral response to Glu56Lys35Phe9

The primary humoral responses of mice to the linear random terpolymerl-Glu⁵⁶-l-Lys³⁵-l-Phe⁹ (GLø) were studied, utilizing the Farr antigen-binding technique and a new hemagglutination assay. This new hemagglutinin assay was easier and more convenient than the conventional Farr method, and was more sensitive in detecting early IgM responses. Following primary immunization, the majority of antibodies produced by responder strains were 2-ME-sensitive. These 2-ME-sensitive antibodies chromatographed at the same relative position as IgM on a Sepharose 6B column. On the other hand, no antibodies of either the IgM or IgG class could be detected in nonresponder strains. These data are consistent with the hypothesis that two complementingIr genes are required for the primary IgM response to GLø, in contrast to findings previously reported for (T,G)-A — L, anotherH-2-linked, complementing,Ir gene system. The implications of these differences are discussed.     

肺心病患者血清甲状腺激素的变化

本文分析30例慢性肺心病心衰并呼衰患者(心衰并呼衰组)及30例慢性肺心病心衰无呼衰患者(心衰无呼哀组)和慢性肺心病死亡组的血清甲状腺激素水平。结果表明心衰并呼衰组T_3、T_4水平均值显著低于心衰无呼衰组和健康组,心衰无呼衰组T_3水平均值显著低于健康组,肺心病死亡组T_3、T_4水平均值显著低于存活组,并发现血清T_3、T_4水平与动脉血氧分压(PaO_2)呈正相关。作者认为T_3明显降低是重症肺心病的损伤性结果,预示病情严重,预后差。而T_4明显下降,可能是死亡的信号之一。     

固定化葡萄糖异构酶最适pH值的调节

用多孔强碱性三乙醇胺基聚苯乙烯树脂作为载体,用CNBr与载体上多羟基作用共价偶联葡萄糖异构酶(GI)。最适偶联条件表明:CNBr量增多,蛋白载量增加,但比活下降。固定化葡萄糖异构酶(IGI)最适反应温度比天然酶提高15℃。并系统地研究了影响IGI活力-pH的曲线的各种因素:用具有不同平均孔径的载体(R=137A,185A,230A,365A)固定化GI,在低离子强度条件下(0.0064mol/L),测定其最适pH值分别7.76,7.56,7.50,8.20。选择平均孔径为230A且具有不同数量三乙醇胺基的载体(0.94,1.05,1.13,1.37mmol/g干胶)分别固定化GI,其最适pH值分别为7.70,7.50,7.46,7.36。     

The effects of isotonic contractions on the rate of fatigue development and the resting membrane potential in the sartorius muscle of the frog, Rana pipiens.

The goal of this study was to characterize how isotonic contractions affect the rate of fatigue development. Muscle bundles dissected from frog sartorius muscles were stimulated with 100-ms long train of pulses (0.5 ms, 6 V, 140 Hz). To measure the effect of the isotonic contractions, isometric tetanus were elicited at regular time intervals during the stimulation to fatigue. In general, isotonic contractions caused a faster decrease in tetanic force than isometric contractions. The difference in tetanic force between an isotonic and isometric fatigue increased gradually over a 20-min period to 7.9 and 13.5% at 0.04 and 0.1 trains/s (TPS), respectively. At 0.2, 0.5, and 1.0 TPS, the decrease in tetanic force was also faster during an isotonic fatigue, which resulted in an initial difference in tetanic force between the two types of fatigue. The difference did not exceed 18.5% and did not persist throughout the stimulation period; i.e., the difference disappeared before the end of the fatigue stimulation. The half-relaxation time was prolonged during fatigue development, and the prolongation was greater during an isotonic fatigue, except at 0.04 TPS. The increases in the half-relaxation time at 0.2, 0.5, and 1.0 TPS were followed by a decrease, and the decreases were especially pronounced during an isotonic fatigue at 0.5 and 1.0 TPS. The results showed for the first time that isotonic contractions cause a faster rate of fatigue development in frog sartorius muscles, and this effect depends on the frequency of stimulation.     

Protein ubiquitination is regulated by phosphorylation. An in vitro study.

Protein ubiquitination has been implicated in ATP-dependent protein turnover and in a number of biological processes in eukaryotic cells. The ubiquitination activating enzyme, E1, and ubiquitin carrier protein, E2, are two essential enzymes in the protein ubiquitination machinery. Using purified E1 and E2 from rabbit reticulocytes and various protein kinases, which include cAMP-dependent protein kinase, protein kinase C, and protein tyrosine kinase, we demonstrated that E1 is phosphorylated by protein kinase C, with a stoichiometry of 0.65 mol of phosphate/mol of E1, and one of the E2 isoforms, E2(32kDa), is phosphorylated by protein tyrosine kinase to 2 eq of phosphate/mol of protein. Phosphorylation of E1 causes a 2-fold enhancement of its activity as monitored by ubiquitin-dependent ATP in equilibrium PPi exchange. When 1 eq of phosphate was incorporated into E2(32kDa), a 2.4-fold activation was also observed for its activity to catalyze the ubiquitination of histone H2A. The regulatory significance of this finding is discussed.