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51.
52.
Malaria results in up to 2.5 million deaths annually, with young children and pregnant women at greatest risk. The great
majority of severe disease is caused by Plasmodium falciparum. A characteristic feature of infection with P. falciparum is the accumulation or sequestration of parasite-infected red blood cells (RBCs) in various organs, such as the brain, lung
and placenta, and together with other factors is important in the pathogenesis of severe forms of malaria. Sequestration results
from adhesive interactions between parasite-derived proteins expressed on the surface of infected RBCs and a number of host
molecules on the surface of endothelial cells, placental cells and uninfected RBCs. Some receptors for parasite adhesion have
been implicated in particular malaria syndromes, such as intercellular adhesion molecule 1 in cerebral malaria and chondroitin
sulfate A and hyaluronic acid in placental infection. The principal parasite ligand and antigen on the RBC surface, P. falciparum erythrocyte membrane protein 1 encoded by a multigene family termed var, is clonally variant, enabling evasion of specific immune responses. An understanding of these host-parasite interactions
in the context of clinical disease and immunity may reveal potential targets to prevent or treat severe forms of malaria.
Received 25 June 2001; received after revision 22 August 2001; accepted 24 August 2001 相似文献
53.
Genetic analysis of the mouse brain proteome 总被引:24,自引:0,他引:24
Klose J Nock C Herrmann M Stühler K Marcus K Blüggel M Krause E Schalkwyk LC Rastan S Brown SD Büssow K Himmelbauer H Lehrach H 《Nature genetics》2002,30(4):385-393
Proteome analysis is a fundamental step in systematic functional genomics. Here we have resolved 8,767 proteins from the mouse brain proteome by large-gel two-dimensional electrophoresis. We detected 1,324 polymorphic proteins from the European collaborative interspecific backcross. Of these, we mapped 665 proteins genetically and identified 466 proteins by mass spectrometry. Qualitatively polymorphic proteins, to 96%, reflect changes in conformation and/or mass. Quantitatively polymorphic proteins show a high frequency (73%) of allele-specific transmission in codominant heterozygotes. Variations in protein isoforms and protein quantity often mapped to chromosomal positions different from that of the structural gene, indicating that single proteins may act as polygenic traits. Genetic analysis of proteomes may detect the types of polymorphism that are most relevant in disease-association studies. 相似文献
54.
Bentley SD Chater KF Cerdeño-Tárraga AM Challis GL Thomson NR James KD Harris DE Quail MA Kieser H Harper D Bateman A Brown S Chandra G Chen CW Collins M Cronin A Fraser A Goble A Hidalgo J Hornsby T Howarth S Huang CH Kieser T Larke L Murphy L Oliver K O'Neil S Rabbinowitsch E Rajandream MA Rutherford K Rutter S Seeger K Saunders D Sharp S Squares R Squares S Taylor K Warren T Wietzorrek A Woodward J Barrell BG Parkhill J Hopwood DA 《Nature》2002,417(6885):141-147
Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering. 相似文献
55.
Bejaoui K Wu C Scheffler MD Haan G Ashby P Wu L de Jong P Brown RH 《Nature genetics》2001,27(3):261-262
Hereditary sensory neuropathy type 1 (HSN1, MIM 162400; ref. 1) genetically maps to human chromosome 9q22 (refs. 2-4). We report here that the gene encoding a subunit of serine palmitoyltransferase is located within the HSN1 locus, expressed in dorsal root ganglia (DRG) and mutated in HSN1. 相似文献
56.
A radiation hybrid map of mouse genes 总被引:13,自引:0,他引:13
Hudson TJ Church DM Greenaway S Nguyen H Cook A Steen RG Van Etten WJ Castle AB Strivens MA Trickett P Heuston C Davison C Southwell A Hardisty R Varela-Carver A Haynes AR Rodriguez-Tome P Doi H Ko MS Pontius J Schriml L Wagner L Maglott D Brown SD Lander ES Schuler G Denny P 《Nature genetics》2001,29(2):201-205
A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome. 相似文献
57.
Most interpretations of early hominin phylogeny recognize a single early to middle Pliocene ancestral lineage, best represented by Australopithecus afarensis, which gave rise to a radiation of taxa in the late Pliocene. Here we report on new fossils discovered west of Lake Turkana, Kenya, which differ markedly from those of contemporary A. afarensis, indicating that hominin taxonomic diversity extended back, well into the middle Pliocene. A 3.5 Myr-old cranium, showing a unique combination of derived facial and primitive neurocranial features, is assigned to a new genus of hominin. These findings point to an early diet-driven adaptive radiation, provide new insight on the association of hominin craniodental features, and have implications for our understanding of Plio-Pleistocene hominin phylogeny. 相似文献
58.
59.
Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells 总被引:27,自引:0,他引:27
Nauli SM Alenghat FJ Luo Y Williams E Vassilev P Li X Elia AE Lu W Brown EM Quinn SJ Ingber DE Zhou J 《Nature genetics》2003,33(2):129-137
Several proteins implicated in the pathogenesis of polycystic kidney disease (PKD) localize to cilia. Furthermore, cilia are malformed in mice with PKD with mutations in TgN737Rpw (encoding polaris). It is not known, however, whether ciliary dysfunction occurs or is relevant to cyst formation in PKD. Here, we show that polycystin-1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by Pkd1 and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD, co-distribute in the primary cilia of kidney epithelium. Cells isolated from transgenic mice that lack functional PC1 formed cilia but did not increase Ca(2+) influx in response to physiological fluid flow. Blocking antibodies directed against PC2 similarly abolished the flow response in wild-type cells as did inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins, phospholipase C and InsP(3) receptors had no effect. These data suggest that PC1 and PC2 contribute to fluid-flow sensation by the primary cilium in renal epithelium and that they both function in the same mechanotransduction pathway. Loss or dysfunction of PC1 or PC2 may therefore lead to PKD owing to the inability of cells to sense mechanical cues that normally regulate tissue morphogenesis. 相似文献
60.
Wnt proteins are lipid-modified and can act as stem cell growth factors 总被引:93,自引:0,他引:93
Willert K Brown JD Danenberg E Duncan AW Weissman IL Reya T Yates JR Nusse R 《Nature》2003,423(6938):448-452
Wnt signalling is involved in numerous events in animal development, including the proliferation of stem cells and the specification of the neural crest. Wnt proteins are potentially important reagents in expanding specific cell types, but in contrast to other developmental signalling molecules such as hedgehog proteins and the bone morphogenetic proteins, Wnt proteins have never been isolated in an active form. Although Wnt proteins are secreted from cells, secretion is usually inefficient and previous attempts to characterize Wnt proteins have been hampered by their high degree of insolubility. Here we have isolated active Wnt molecules, including the product of the mouse Wnt3a gene. By mass spectrometry, we found the proteins to be palmitoylated on a conserved cysteine. Enzymatic removal of the palmitate or site-directed and natural mutations of the modified cysteine result in loss of activity, and indicate that the lipid is important for signalling. The purified Wnt3a protein induces self-renewal of haematopoietic stem cells, signifying its potential use in tissue engineering. 相似文献