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71.
A. J. Ambrose 《BMJ (Clinical research ed.)》1947,1(4497):353-354
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The pentastomid parasite Porocephalus crotali, develops to an infective stage within a granulomatous lesion in the tissues of rodent intermediate hosts. A conspicuous layer of sub-parietal cell (SPC) secretory product, which coats the intermoult cuticle up to a depth of 12 microns, is described. Around the first five nymphal instars this material consists of an amorphous matrix with distinctive electron-lucid lacunae, but that around later instars (six and seven), while retaining much of the original morphology, possesses a significant membranous component. Host effector cells, most notably eosinophils and macrophage/epithelioid cells, are frequently completely enveloped by SPC secretion but invariably appear unreactive to it. Host cells may penetrate to the outermost layer of the epicuticle but again but again cytotoxic activity is absent. During ecdysis, effector cells are recruited to the intercuticular space where widespread degranulation is evident. Some of this is specifically directed against the underside of the cast cuticle, but not against the newly exposed cuticle. Protracted degranulation eventually reduces the cast cuticle to fragments which are endocytosed by giant cells. 1 cm long infective (seventh-stage) nymphs, which retain the sixth stage cuticle as a protective sheath, are largely devoid of membranous secretion and these were dissected from cysts, washed, and surgically transplanted into the body cavities of naive and infected mice. Pronounced differences in the onset and intensity of the subsequent inflammatory response in the two categories of host indicate some form of specific recognition. In both groups of mice though, the cuticle is an eventual target for attack by effector cells, and parasites are killed. The protective function of SPC secretion is discussed. 相似文献
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Kinase-deficient Pak1 mutants inhibit Ras transformation of Rat-1 fibroblasts. 总被引:8,自引:3,他引:5 下载免费PDF全文
Y Tang Z Chen D Ambrose J Liu J B Gibbs J Chernoff J Field 《Molecular and cellular biology》1997,17(8):4454-4464
Among the mechanisms by which the Ras oncogene induces cellular transformation, Ras activates the mitogen-activated protein kinase (MAPK or ERK) cascade and a related cascade leading to activation of Jun kinase (JNK or SAPK). JNK is additionally regulated by the Ras-related G proteins Rac and Cdc42. Ras also regulates the actin cytoskeleton through an incompletely elucidated Rac-dependent mechanism. A candidate for the physiological effector for both JNK and actin regulation by Rac and Cdc42 is the serine/threonine kinase Pak (p65pak). We show here that expression of a catalytically inactive mutant Pak, Pak1(R299), inhibits Ras transformation of Rat-1 fibroblasts but not of NIH 3T3 cells. Typically, 90 to 95% fewer transformed colonies were observed in cotransfection assays with Rat-1 cells. Pak1(R299) did not inhibit transformation by the Raf oncogene, indicating that inhibition was specific for Ras. Furthermore, Rat-1 cell lines expressing Pak1(R299) were highly resistant to Ras transformation, while cells expressing wild-type Pak1 were efficiently transformed by Ras. Pak1(L83,L86,R299), a mutant that fails to bind either Rac or Cdc42, also inhibited Ras transformation. Rac and Ras activation of JNK was inhibited by Pak1(R299) but not by Pak1(L83,L86,R299). Ras activation of ERK was inhibited by both Pak1(R299) and Pak1(L83,L86,R299), while neither mutant inhibited Raf activation of ERK. These results suggest that Pak1 interacts with components essential for Ras transformation and that inhibition can be uncoupled from JNK but not ERK signaling. 相似文献
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Thure E. Cerling John M. Harris Stanley H. Ambrose Meave G. Leakey Nikos Solounias 《Journal of human evolution》1997,33(6):635-650
Tooth enamel of nine Middle Miocene mammalian herbivores from Fort Ternan, Kenya, was analyzed for δ13C and δ18O. The δ18O values of the tooth enamel compared with pedogenic and diagenetic carbonate confirm the use of stable isotope analysis of fossil tooth enamel as a paleoenvironmental indicator. Furthermore, the δ18O of tooth enamel indicates differences in water sources between some of the mammals. The δ13C values of tooth enamel ranged from −8·6–−13·0‰ which is compatible with a pure C3diet, though the possibility of a small C4fraction in the diet of a few of the specimens sampled is not precluded. The carbon isotopic data do not support environmental reconstructions of a Serengeti-typed wooded grassland with a significant proportion of C4grasses. This study does not preclude the presence of C3grasses at Fort Ternan; it is possible that C3grasses could have had a wider geographic range if atmospheric CO2levels were higher than the present values. 相似文献
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The ampicillin resistance gene fromShigella flexneri2a strain YSH6000 was cloned and shown by Southern hybridization analysis to be closely linked to the previously cloned streptomycin, chloramphenicol, and tetracycline resistance determinants, which are borne on a chromosomally integrated 99-kb element. Analysis of this chromosomal multi-antibiotic resistance locus revealed that it had a high level of sequence and organizational similarity to an equivalent region of theShigellaR-plasmid, NR1. However, the chromosomal locus exhibited several differences, including the presence of two stretches of sequence derived from IS elements, the precise insertion of a β-lactamase encodingoxa1cassette into the Tn21-borne integron In2, a possible 17.5-kb deletion, and the loss or inactivation of the mercury resistance determinant. Based on these data, it is proposed that the chromosomal locus arose following integration of an NR1-like plasmid. 相似文献
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Alice R. Clark Wilma Vree Egberts Frances D.L. Kondrat Gillian R. Hilton Nicholas J. Ray Ambrose R. Cole John A. Carver Justin L.P. Benesch Nicholas H. Keep Wilbert C. Boelens Christine Slingsby 《Journal of molecular biology》2018,430(18):3297-3310
Heterogeneity in small heat shock proteins (sHsps) spans multiple spatiotemporal regimes—from fast fluctuations of part of the protein, to conformational variability of tertiary structure, plasticity of the interfaces, and polydispersity of the inter-converting, and co-assembling oligomers. This heterogeneity and dynamic nature of sHsps has significantly hindered their structural characterization. Atomic coordinates are particularly lacking for vertebrate sHsps, where most available structures are of extensively truncated homomers. sHsps play important roles in maintaining protein levels in the cell and therefore in organismal health and disease. HspB2 and HspB3 are vertebrate sHsps that are found co-assembled in neuromuscular cells, and variants thereof are associated with disease. Here, we present the structure of human HspB2/B3, which crystallized as a hetero-tetramer in a 3:1 ratio. In the HspB2/B3 tetramer, the four α-crystallin domains (ACDs) assemble into a flattened tetrahedron which is pierced by two non-intersecting approximate dyads. Assembly is mediated by flexible “nuts and bolts” involving IXI/V motifs from terminal regions filling ACD pockets. Parts of the N-terminal region bind in an unfolded conformation into the anti-parallel shared ACD dimer grooves. Tracts of the terminal regions are not resolved, most likely due to their disorder in the crystal lattice. This first structure of a full-length human sHsp heteromer reveals the heterogeneous interactions of the terminal regions and suggests a plasticity that is important for the cytoprotective functions of sHsps. 相似文献