Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite

As the malaria parasite, Plasmodium falciparum, grows within its host erythrocyte it induces an increase in the permeability of the erythrocyte membrane to a range of low-molecular-mass solutes, including Na+ and K+ (ref. 1). This results in a progressive increase in the concentration of Na+ in the erythrocyte cytosol. The parasite cytosol has a relatively low Na+ concentration and there is therefore a large inward Na+ gradient across the parasite plasma membrane. Here we show that the parasite exploits the Na+ electrochemical gradient to energize the uptake of inorganic phosphate (P(i)), an essential nutrient. P(i) was taken up into the intracellular parasite by a Na+-dependent transporter, with a stoichiometry of 2Na+:1P(i) and with an apparent preference for the monovalent over the divalent form of P(i). A P(i) transporter (PfPiT) belonging to the PiT family was cloned from the parasite and localized to the parasite surface. Expression of PfPiT in Xenopus oocytes resulted in Na+-dependent P(i) uptake with characteristics similar to those observed for P(i) uptake in the parasite. This study provides new insight into the significance of the malaria-parasite-induced alteration of the ionic composition of its host cell.     

DNA sequence and analysis of human chromosome 8

The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution.     

Positional cloning of a novel gene influencing asthma from chromosome 2q14

Asthma is a common disease in children and young adults. Four separate reports have linked asthma and related phenotypes to an ill-defined interval between 2q14 and 2q32 (refs. 1-4), and two mouse genome screens have linked bronchial hyper-responsiveness to the region homologous to 2q14 (refs. 5,6). We found and replicated association between asthma and the D2S308 microsatellite, 800 kb distal to the IL1 cluster on 2q14. We sequenced the surrounding region and constructed a comprehensive, high-density, single-nucleotide polymorphism (SNP) linkage disequilibrium (LD) map. SNP association was limited to the initial exons of a solitary gene of 3.6 kb (DPP10), which extends over 1 Mb of genomic DNA. DPP10 encodes a homolog of dipeptidyl peptidases (DPPs) that cleave terminal dipeptides from cytokines and chemokines, and it presents a potential new target for asthma therapy.     

Thymic cortical epithelial cells can present self-antigens in vivo

Antigens present during neonatal life are recognized as self and individuals are tolerant to these antigens. In normal individuals T cells are tolerant to most self proteins but we still know little of the mechanism(s) by which tolerance is established. A requisite part of the current negative selection model of self tolerance is the expression of self proteins complexed with major histocompatibility complex molecules in the thymus. As MHC proteins bind antigens and present them to the receptor on the antigen-specific T cell, then for tolerance to self to occur, it is possible that each self protein must be processed and presented by an MHC molecule. As a result of the development of a unique T-cell hybrid reactive to the self protein murine haemoglobin, we have shown that in normal animals this self protein is continuously processed and potentially presented in an MHC-restricted manner. Here we show that self haemoglobin is being processed and presented by thymic antigen-presenting cells as early as gestational day 14. We also demonstrate that three types of thymic stromal cells, namely macrophages, dendritic cells and cortical epithelial cells, can present the haemoglobin self antigen in vivo. This surprising presentation of a self antigen by thymic cortical epithelial cells implies that they could be involved in T-cell development and negative selection.     

Thymic cortical epithelial cells lack full capacity for antigen presentation

Several recent studies have suggested that interactions between thymocytes and thymic stromal cells are essential for the development and elimination of antigen-reactive T lymphocytes. It is important, therefore, to characterize the stromal cells involved in presentation of antigen in the thymus. In a previous report, we demonstrated, using T-cell hybridomas, that three distinct types of antigen presenting cells in the thymus (cortical epithelial cells, macrophages, and dendritic cells) constitutively expressed self haemoglobin/Ia complexes. Here we report that one of these cell types, the cortical epithelial cell, does not induce stimulation of T-lymphocyte clones even though the antigen/Ia complex required for antigen-specific recognition is present. This lack of response occurs with both TH1 and TH2 clones. Responsiveness of the TH2 clone can be restored by adding the murine lymphokine interleukin-1 beta to the culture system.     

基于现场总线的开放式数控系统体系结构研究

结合现场总线的特点和开放式系统的要求，提出了一种基于现场总线的开放式CNC系统的体系结构，并把该体系划分为应用层，功能层和设备层三个层次，对每一层的功能进行了系统的分析和描述。在实现方法上，采用COM／DCOM技术的OPC规范的软件方法，实现了数控系统的软件 模块的重用与扩充；采用Profibus现场总线实现了数控系统的硬件模块的互操作与互换，从而满足了数控系统开放性的要求。