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91.
Frank M Kirkman L Costantini D Sanyal S Lavazec C Templeton TJ Deitsch KW 《International journal for parasitology》2008,38(10):1099-1109
The human malaria parasite Plasmodium falciparum utilises a mechanism of antigenic variation to avoid the antibody response of its human host and thereby generates a long-term, persistent infection. This process predominantly results from systematic changes in expression of the primary erythrocyte surface antigen, a parasite-produced protein called PfEMP1 that is encoded by a repertoire of over 60 var genes in the P. falciparum genome. var genes exhibit extensive sequence diversity, both within a single parasite's genome as well as between different parasite isolates, and thus provide a large repertoire of antigenic determinants to be alternately displayed over the course of an infection. Whilst significant work has recently been published documenting the extreme level of diversity displayed by var genes found in natural parasite populations, little work has been done regarding the mechanisms that lead to sequence diversification and heterogeneity within var genes. In the course of producing transgenic lines from the original NF54 parasite isolate, we cloned and characterised a parasite line, termed E5, which is closely related to but distinct from 3D7, the parasite used for the P. falciparum genome nucleotide sequencing project. Analysis of the E5 var gene repertoire, as well as that of the surrounding rif and stevor multi-copy gene families, identified examples of frequent recombination events within these gene families, including an example of a duplicative transposition which indicates that recombination events play a significant role in the generation of diversity within the antigen encoding genes of P. falciparum. 相似文献
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We have examined cytokeratin distribution and their nature in toe pads of the Himalayan tree-frog Philautus annandalii. Toe pads are expanded tips of digits and show modifications of their ventral epidermis for adhesion. The toe pad epidermal cells, being organized into 3–4 rows, possess keratin bundles, especially in surface nanostructures that are involved in adhesion. Immunohistochemical localization using a pan-cytokeratin antibody revealed that cytokeratin immunoreactivity is the strongest in the mid- to basal cell rows of the epidermis, which parallels our previous ultrastructural observation of dense keratin bundles present in this part of the epidermis. The remainder of the epidermis (i.e., the superficial cell layer) showed little immunoreactivity. Immunoblot analysis revealed that toe-pads possessed keratins prominently in the molecular mass of 50 kDa. Possible presence of keratin 5 in toe pad epidermis has been correlated with its usual distribution pattern in mammalian epidermis. 相似文献
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Grzegorzewski KJ Yao XT Kreider B Olsen HS Morris TS Zhang L Sanyal I Nardelli B Zukauskas D Brewer L Bong GW Kim Y Garotta G Salcedo TW 《Cytokine》2001,13(4):209-219
Myeloid progenitor inhibitory factor (MPIF)-2 is a beta-chemokine with select and potent activities on eosinophils and myeloid progenitors. In the beta-chemokine family, biological activity is modulated by differential processing of the amino-terminus. Here, for MPIF-2, we describe the biological activities of NH(2)-terminal deletion mutants and compare regions necessary for eosinophil and myeloid progenitor activities. Five MPIF-2 proteins with deletions at the amino-terminus were produced in Escherichia coli and assayed for calcium mobilization, chemotaxis and receptor binding activities on eosinophils, and for their ability to inhibit colony formation of human myeloid bone marrow progenitors. For eosinophils, deletion of the first two amino acids did not markedly alter activity, while subsequent truncations result in a complete loss of activity. One of the MPIF-2 mutants, MPIF-2 (P30-R99) was converted from an agonist to an antagonist of eotaxin, MPIF-2 and MCP-4 functional responses in eosinophil calcium flux and chemotaxis assays. Surprisingly, while displaying a complete loss of agonist activity toward eosinophils, MPIF-2 (P30-R99) retains ability to inhibit human bone marrow myeloid progenitor cell colony formation. In addition, processing at the amino terminus of MPIF-2 in vivo, may result in a chemokine with altered biological activities. 相似文献
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Sabyasachi Das Masayuki Hirano Rea Tako Chelsea McCallister Nikolas Nikolaidis 《Current Genomics》2012,13(2):95-102
Immunoglobulins (or antibodies) are an essential element of the jawed vertebrate adaptive immune response system. These molecules have evolved over the past 500 million years and generated highly specialized proteins that recognize an extraordinarily large number of diverse substances, collectively known as antigens. During vertebrate evolution the diversification of the immunoglobulin-encoding loci resulted in differences in the genomic organization, gene content, and ratio of functional genes and pseudogenes. The tinkering process in the immunoglobulin-encoding loci often gave rise to lineage-specific characteristics that were formed by selection to increase species adaptation and fitness. Immunoglobulin loci and their encoded antibodies have been shaped repeatedly by contrasting evolutionary forces, either to conserve the prototypic structure and mechanism of action or to generate alternative and diversified structures and modes of function. Moreover, evolution favored the development of multiple mechanisms of primary and secondary antibody diversification, which are used by different species to effectively generate an almost infinite collection of diverse antibody types. This review summarizes our current knowledge on the genomics and evolution of the immunoglobulin-encoding loci and their protein products in jawed vertebrates. 相似文献
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