Plasmodium falciparum malaria: band 3 as a possible receptor during invasion of human erythrocytes

Human erythrocyte band 3, a major membrane-spanning protein, was purified and incorporated into liposomes. These liposomes, at nanomolar concentrations of protein, inhibited invasion of human erythrocytes in vitro by the malaria parasite Plasmodium falciparum. Liposomes containing human band 3 were ten times more effective in inhibiting invasion than those with pig band 3 and six times more effective than liposomes containing human erythrocyte glycophorin. Liposomes alone or liposomes containing erythrocyte glycolipids did not inhibit invasion. These results suggest that band 3 participates in the invasion process in a step involving a specific, high-affinity interaction between band 3 and some component of the parasite.     

Antigens induced on erythrocytes by P. falciparum: expression of diverse and conserved determinants

Red blood cells that are infected with the malaria parasite Plasmodium falciparum express new antigens on their surface. In a study of these antigens in the erythrocytes of naturally infected children in the Gambia, an antibody-mediated agglutination assay revealed an extreme degree of antigenic diversity. Serum samples from each of ten children in the convalescent stage of malaria infection reacted with infected cells from the same child but generally not with infected cells from the other children. The Gambian children's erythrocytes also expressed shared determinants: sera from Gambian adults often reacted with the surface of infected cells from all of the children and were shown by adsorption and elution experiments to contain antibodies that recognized several isolates. Conserved determinants exposed on infected erythrocytes may be important for development of antimalarial immunity either naturally or through vaccination.     

The Plasmodium falciparum genome--a blueprint for erythrocyte invasion

Erythrocyte invasion by Plasmodium falciparum involves multiple ligand-receptor interactions and numerous apparent redundancies. The genome sequence of this parasite reveals new gene families encoding proteins that appear to mediate erythrocyte invasion.     

Epitopes recognized by human T cells map within the conserved part of the GP190 of P. falciparum

In a study aimed at developing a vaccine against the asexual blood stages of Plasmodium falciparum, two T cell epitopes were identified within a nonpolymorphic region of gp190 of Plasmodium falciparum merozoites. The two epitopes, which were revealed by deletion analysis, stimulated human T cell clones. Peptides containing sequences of the epitopes stimulated the cloned T cells and peripheral blood mononuclear cells (PBMC) from malaria-infected individuals. Moreover, the T cell clones responded to 11 different Plasmodium falciparum isolates in culture, showing that the epitopes are recognized in native parasites.     

A bond-fluctuation mechanism for stochastic switching in wired molecules

Stochastic on-off conductivity switching observed in phenylene-ethynylene oligomers has been explained in terms of changes in ring conformations, or electron localization, or both. We report the observation of stochastic on-off switching in the simplest of wired molecules: octanedithiol, decanedithiol, and dodecanedithiol bonded on an Au(111) surface. Stochastic switching was observed even when a top gold contact was pressed on by a conducting atomic force microscope tip at constant force. The rate of switching increased substantially at 60 degrees C, a temperature at which these films are commonly annealed. Because such switching in alkanethiols is unlikely to be caused by internal molecular electronic changes and cannot be fully accounted for by breaking of the top contact, we argue that the cause is the well-known mobility of molecules tethered to gold via a thiol linkage.     

植物硼营养高效的分子调控途径

植物体内的硼主要存在于细胞壁中,对稳定细胞壁结构和促进生长发育起重要作用。双子叶植物需硼多,对缺硼敏感,但不同物种及不同品种对缺硼的抗性存在极显著的基因型差异。华中农业大学王运华教授在1990年代带领团队开展甘蓝型油菜硼高效品种的筛选,从此开启了我国植物硼营养高效利用的遗传与分子机制研究。近10多年的研究结果表明,植物响应缺硼胁迫提高硼效率存在2条不同的分子调控途径。（1）依赖硼转运基因的途径。在这条途径中,NIPs和BORs家族基因受缺硼诱导表达增强根系对土壤硼的吸收和体内硼的转运分配,实现硼的高效吸收和转运,进而提高植物对缺硼胁迫的抗性或适应性;（2）独立于硼转运基因的途径。该途径中,植物通过影响激素信号和细胞壁合成代谢相关基因的表达,调节根系生长发育和细胞壁组分结构等方式,提高体内硼的利用效率,进而增强植物对缺硼的抗性。在硼被确定为植物必需营养元素的百年纪念之际,我们对这一工作进行综述归纳,以飨读者。同时,在王运华先生逝世1周年之际,深切缅怀先生在开启华中农业大学作物硼营养遗传研究领域中所做的奠基性贡献。     

类风湿关节炎治疗药物的分子作用机制研究进展

类风湿关节炎是慢性自体免疫性疾病,文章从作用于细胞因子及其受体、针对T淋巴细胞的清除、影响G蛋白偶联受体信号转导和Ras-丝裂原激活的蛋白激酶信号转导四个方面阐述了消炎免疫药物治疗类风湿性关节炎的分子作用机制。     

Molecular pathways of neurodegeneration in Parkinson's disease

Parkinson's disease (PD) is a complex disorder with many different causes, yet they may intersect in common pathways, raising the possibility that neuroprotective agents may have broad applicability in the treatment of PD. Current evidence suggests that mitochondrial complex I inhibition may be the central cause of sporadic PD and that derangements in complex I cause alpha-synuclein aggregation, which contributes to the demise of dopamine neurons. Accumulation and aggregation of alpha-synuclein may further contribute to the death of dopamine neurons through impairments in protein handling and detoxification. Dysfunction of parkin (a ubiquitin E3 ligase) and DJ-1 could contribute to these deficits. Strategies aimed at restoring complex I activity, reducing oxidative stress and alpha-synuclein aggregation, and enhancing protein degradation may hold particular promise as powerful neuroprotective agents in the treatment of PD.     

Reversible switching of hydrogel-actuated nanostructures into complex micropatterns

Responsive behavior, which is intrinsic to natural systems, is becoming a key requirement for advanced artificial materials and devices, presenting a substantial scientific and engineering challenge. We designed dynamic actuation systems by integrating high-aspect-ratio silicon nanocolumns, either free-standing or substrate-attached, with a hydrogel layer. The nanocolumns were put in motion by the "muscle" of the hydrogel, which swells or contracts depending on the humidity level. This actuation resulted in a fast reversible reorientation of the nanocolumns from tilted to perpendicular to the surface. By further controlling the stress field in the hydrogel, the formation of a variety of elaborate reversibly actuated micropatterns was demonstrated. The mechanics of the actuation process have been assessed. Dynamic control over the movement and orientation of surface nanofeatures at the micron and submicron scales may have exciting applications in actuators, microfluidics, or responsive materials.     

Molecular biology. Targeting intron insertion into DNA

In work reported on page 452, researchers have found a way to coax certain introns, bits of genetic debris that litter the DNA and interrupt the coding sequences of many genes, to hop into the exact sequences where the researchers want them. The method could enhance all sorts of genetic manipulations, from studying basic gene function to combating viral infections to delivering genes for gene therapy.     

Effect of antibodies to recombinant and synthetic peptides on P. falciparum sporozoites in vitro

Antibodies were raised in mice immunized with several recombinant and synthetic peptides of the circumsporozoite protein of Plasmodium falciparum. The antibodies were evaluated for protective activity in a human hepatocyte culture system. They exerted their protective effect against the parasite at three points: sporozoite attachment to the hepatocyte surface, entry, and subsequent intracellular development. Inhibition of attachment and entry were found to be related to the antibody titer against the authentic circumsporozoite protein on the sporozoite surface, especially when peptides were administered with alum or complete Freund's adjuvant. Even when invasion was not totally inhibited, the presence of abnormal trophozoites and a frequent inhibition of schizont development in long-term cultures suggested continued activity of antibodies at the intracellular level after sporozoite penetration had been completed.     

胚泡植入的分子机理

胚泡植入是在各级因子组成的复杂网络系统调节下,胚泡与子宫内膜相互识别、定位、轴附和侵入,从而使胚泡成功地植入。目前的研究表明,许多活性分子参与胚胎植入的调节过程,而对细胞因子和生长因子及其受体的相互作用及整合素受体与其配体相互作用所引起信号转导的研究,将对揭示子宫内膜变化和胚泡植入的分子机理具有重要意义。     

Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance

Chloroquine-resistant Plasmodium falciparum accumulate significantly less chloroquine than susceptible parasites, and this is thought to be the basis of their resistance. However, the reason for the lower accumulation of chloroquine was unknown. The resistant parasite has now been found to release chloroquine 40 to 50 times more rapidly than the susceptible parasite, although their initial rates of chloroquine accumulation are the same. Verapamil and two other calcium channel blockers, as well as vinblastine and daunomycin, each slowed the release and increased the accumulation of chloroquine by resistant (but not susceptible) Plasmodium falciparum. These results suggest that a higher rate of chloroquine release explains the lower chloroquine accumulation, and thus the resistance observed in resistant Plasmodium falciparum.     

Genetic analysis of the human malaria parasite Plasmodium falciparum

Malaria parasites are haploid for most of their life cycle, with zygote formation and meiosis occurring during the mosquito phase of development. The parasites can be analyzed genetically by transmitting mixtures of cloned parasites through mosquitoes to permit cross-fertilization of gametes to occur. A cross was made between two clones of Plasmodium falciparum differing in enzymes, drug sensitivity, antigens, and chromosome patterns. Parasites showing recombination between the parent clone markers were detected at a high frequency. Novel forms of certain chromosomes, detected by pulsed-field gradient gel electrophoresis, were produced readily, showing that extensive rearrangements occur in the parasite genome after cross-fertilization. Since patients are frequently infected with mixtures of genetically distinct parasites, mosquito transmission is likely to provide the principal mechanisms for generating parasites with novel genotypes.     

Invasive plants versus their new and old neighbors: a mechanism for exotic invasion

Invading exotic plants are thought to succeed primarily because they have escaped their natural enemies, not because of novel interactions with their new neighbors. However, we find that Centaurea diffusa, a noxious weed in North America, has much stronger negative effects on grass species from North America than on closely related grass species from communities to which Centaurea is native. Centaurea's advantage against North American species appears to be due to differences in the effects of its root exudates and how these root exudates affect competition for resources. Our results may help to explain why some exotic species so successfully invade natural plant communities.