Hemoglobin catabolism and the killing of intraerythrocytic<Emphasis Type="Italic">Plasmodium falciparum</Emphasis> by chloroquine

To evaluate how chloroquine kills malaria parasites, hemoglobin catabolism was studied at the various stages of intraerythrocytic parasite development. We found that hemoglobin catabolism is switched off whenPlasmodium falciparum parasites mature to the late trophozoite or early schizont stages and is switched on again during the ring stage. When hemoglobin catabolism is switched off, the parasites are resistant to the morphologic effects of chloroquine. Although the ring stage parasites failed to mature in the presence of chloroquine, some of them switched on hemoglobin ingestion and became stuffed with hemoglobin-filled vesicles, indicating a distal block in catabolism. In fact, we demonstrated a high-grade block in hemozoin production during a 22 h incubation of synchronized ring forms; ferriprotoporphyrin IX (FP) incorporation into the β-hematin of hemozoin decreased from 900 to 50 pmol/10⁶ parasitized erythrocytes. We propose that the primary effect of chloroquine on hemoglobin catabolism is to block FP polymerization to β-hematin. Secondarily, toxic FP and FP-chloroquine complexes accumulate and are available to exert their several toxicities, which include inhibition of hemoglobindegrading proteases and membrane damage. As a consequence, maturation is arrested and eventually the parasites die and lyse.     

Biochemical aspects of radiation biology

Summary In order to analyze the mechanisms of biological radiation effects, the events after radiation energy absorption in irradiated organisms have to be studied by physico-chemical and biochemical methods. The radiation effects in vitro on biomolecules, especially DNA, are described, as well as their alterations in irradiated cells. Whereas in vitro, in aqueous solution, predominantly OH radicals are effective and lead to damage in single moieties of the DNA, in vivo the direct absorption of radiation energy leads to locally multiply-damaged sites, which produce DNA double-strand breaks and locally denatured regions. DNA damage will be repaired in irradiated cells. Error free repair leads to the original nucleotide sequence in the genome by excision or by recombination. Error prone repair (mutagenic repair), leads to mutation. However, the biochemistry of these processes, regulated by a number of genes, is poorly understood. In addition, more complex reactions, such as gene amplification and transposition of mobile gene elements, are responsible for mutation or malignant transformation.     

Bioassay for hamster macrophage chemotaxis: application to study particle-lung interactions

Attraction of lung macrophages to particle deposition sites has been demonstrated in different animal species. We reported a threefold increase of the number of macrophages to occur within 40 min after polystyrene particle deposition in hamster airways [Geiser et al. (1994) Am. J. Respir. Cell Mol. Biol. 160: 594–603]. Complement-derived chemotactic activity is one of the mechanisms postulated for macrophage recruitment. It was the aim of this study to test whether complement-derived chemotactic activity is involved in the rapid recruitment of macrophages to the site of deposited polystyrene particles in hamster airways. We first developed an in vitro cell migration assay for hamster macrophages to assess complement-derived chemotaxis. Second, the bronchoalveolar lavage fluids (BALF) of four hamsters that had inhaled aerosols of polystyrene microspheres were tested for chemotactic activity by this bioassay and compared with BALF of four sham-exposed hamsters. Chemotactic response of macrophages was found toward complement-activated hamster serum, whereas macrophage migration was not increased toward BALF of particle and sham-exposed hamsters. In contrast, macrophage migration to BALF of both groups was reduced by 1.6-fold. Thus, the stimulus for macrophage recruitment to the site of deposited polystyrene particles in hamster airways could not be demonstrated using this bioassay. Received 10 September 1997; received after revision 24 November 1997; accepted 10 December 1997     

On the origin of species by sympatric speciation.

Understanding speciation is a fundamental biological problem. It is believed that many species originated through allopatric divergence, where new species arise from geographically isolated populations of the same ancestral species. In contrast, the possibility of sympatric speciation (in which new species arise without geographical isolation) has often been dismissed, partly because of theoretical difficulties. Most previous models analysing sympatric speciation concentrated on particular aspects of the problem while neglecting others. Here we present a model that integrates a novel combination of different features and show that sympatric speciation is a likely outcome of competition for resources. We use multilocus genetics to describe sexual reproduction in an individual-based model, and we consider the evolution of assortative mating (where individuals mate preferentially with like individuals) depending either on an ecological character affecting resource use or on a selectively neutral marker trait. In both cases, evolution of assortative mating often leads to reproductive isolation between ecologically diverging subpopulations. When assortative mating depends on a marker trait, and is therefore not directly linked to resource competition, speciation occurs when genetic drift breaks the linkage equilibrium between the marker and the ecological trait. Our theory conforms well with mounting empirical evidence for the sympatric origin of many species.     

Über die Chemie des Enniatins

Summary Judging by the physical and chemical properties and bacterial spectra, the antibiotic substance, Enniatin, previously isolated from a strain ofFusarium by the authors, appears to be identical with that which was recently reported byCook et al. derived from another strain and designated by them as Lateritiin-I, although the reported empirical formulæ differ. Numerous physical and chemical characteristics of Enniatin and its degradation products are given, and, further, two relatedFusarium antibiotics, here designated as Enniatin B and C, are briefly described.

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Ausgeführt mit einem Beitrag aus den eidg. Arbeitsbeschaffungskrediten.     

用自身血清抗体筛选人肝细胞肝癌抗原

为了从分子水平上筛选肝细胞肝癌抗原，应用作者所在实验室创建的“重组克隆表达抗原的血清学鉴定技术”（ＳＥＲＥＸｓｅｒｏｌｏｇｉｃａｌｉｎｄｅｎｔｉｆｉｃａｔｉｏｎｏｆａｎｔｉｇｅｎｓｂｙｒｅｃｏｍｂｉｎａｎｔｅｘｐｒｅｓｉｏｎｃｌｏｎｉｎｇ）筛选人肝细胞肝癌（ＨＣＣ）组织构建的ｃＤＮＡ文库，发现了许多与病人，自身血清高滴度抗体反应的克隆。应用多种异体（其他ＨＣＣ病人，多种非ＨＣＣ肿瘤病人，Ｂ型、Ｃ型病毒性肝炎病人，肝硬化病人以及健康人）血清反应分析表明，高滴度抗体反应多数出现在ＨＣＣ病人。参照基因库寻找这些克隆的同源结构，发现其中许多抗原为至今未知基因所编码。进一步的血清和抗原分子分析将为ＨＣＣ特异免疫治疗和诊断提供基础资料     

中国古代园林空间模式研究——以甘泉宫、武侯墓和黄帝陵为例

借鉴空间理论的有关研究成果,依据空间的2种表现形式即感知空间与认知空间的特征,对园林的空间模式进行了界定与研究,并以汉代园林3大遗产地甘泉宫、武候墓和黄帝陵为例进行实地考察,综合分析.研究结果表明,中国古代园林存有外向型、内向型及内外结合型3种空间模式;外向型是一种开放式的空间模式,其表现为"宽广"与"博大";内向型是一种闭合式的空间模式,其表现为"藏风聚气";内外结合型空间模式是上述2种空间模式的结合.研究揭示出园林空间是一个融合统一的有机整体,提示了园林的空间特征与本质,并为中国古代园林或遗产地的空间鉴赏与旅游开发提供新的思路与依据.     

Attosecond metrology.

The generation of ultrashort pulses is a key to exploring the dynamic behaviour of matter on ever-shorter timescales. Recent developments have pushed the duration of laser pulses close to its natural limit-the wave cycle, which lasts somewhat longer than one femtosecond (1 fs = 10-15 s) in the visible spectral range. Time-resolved measurements with these pulses are able to trace dynamics of molecular structure, but fail to capture electronic processes occurring on an attosecond (1 as = 10-18 s) timescale. Here we trace electronic dynamics with a time resolution of 相似文献