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1.
R Gill C Verma B Wallach B Urs? J Pitts A Wollmer P De Meyts S Wood 《Protein engineering》1999,12(4):297-303
Insulin-like growth factor-1 (IGF-1) is a serum protein which unexpectedly folds to yield two stable tertiary structures with different disulphide connectivities; native IGF-1 [18-61,6-48,47-52] and IGF-1 swap [18-61,6-47, 48-52]. Here we demonstrate in detail the biological properties of recombinant human native IGF-1 and IGF-1 swap secreted from Saccharomyces cerevisiae. IGF-1 swap had a approximately 30 fold loss in affinity for the IGF-1 receptor overexpressed on BHK cells compared with native IGF-1.The parallel increase in dose required to induce negative cooperativity together with the parallel loss in mitogenicity in NIH 3T3 cells implies that disruption of the IGF-1 receptor binding interaction rather than restriction of a post-binding conformational change is responsible for the reduction in biological activity of IGF-1 swap. Interestingly, the affinity of IGF-1 swap for the insulin receptor was approximately 200 fold lower than that of native IGF-1 indicating that the binding surface complementary to the insulin receptor (or the ability to attain it) is disturbed to a greater extent than that to the IGF-1 receptor. A 1.0 ns high-temperature molecular dynamics study of the local energy landscape of IGF-1 swap resulted in uncoiling of the first A-region alpha-helix and a rearrangement in the relative orientation of the A- and B-regions. The model of IGF-1 swap is structurally homologous to the NMR structure of insulin swap and CD spectra consistent with the model are presented. However, in the model of IGF-1 swap the C-region has filled the space where the first A-region alpha-helix has uncoiled and this may be hindering interaction of Val44 with the second insulin receptor binding pocket. 相似文献
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The out of hours workload of a training practice in a suburban and semirural area on the south coast of England was studied for one year. An overall rate of contact of 273/1000 patients was found, which indicated a workload greater than that reported in most other studies. The duty doctor received over 35 telephone calls from patients during some Saturdays (1200 Saturday to 0800 Sunday) and Sundays (0800 to 0800 Monday), up to five being between 2300 and 0700. Of the patients who contacted a general practitioner, 44% were given advice by telephone and 4.9% were admitted to hospital. The admission rate was lower than that given in other studies. A considerable proportion of the workload arose from doctors covering the casualty department of a cottage hospital. Patients having a high expectation of 24 hour care by general practitioners in an area of comparative affluence (Jarman indices -13.8 to 1.7) may account for this aspect of the workload. 相似文献
5.
Splenic B cells from DBA/2 and NZB mice were compared with regard to precursor frequency of anti-ssDNA-producing cells. Using a modification of the splenic fragment assay, we show that NZB T cells are capable of increasing the frequency of expression of anti-ssDNA precursors in DBA/2 splenic B cells. When limiting numbers of splenic B cells of DBA/2 origin were adoptively transferred into an irradiated (1200 rad) recipient, the co-transfer of NZB T cells markedly increased the frequency of anti-ssDNA precursors in cultured splenic fragments. The anti-ssDNA produced under these conditions was exclusively IgM and exhibited a high degree of cross-reactivity with TNP and fluorescein. Thus, the increase in anti-ssDNA precursor frequency reflected an expansion of the B cell repertoire to include precursors of polyspecific antibody-producing cells that under normal circumstances are not expressed. The ability of NZB T cells to increase the anti-ssDNA precursor frequency was further defined by the CBA/N immunodeficiency gene xid, in that B cells from DBA/2.xid donors did not exhibit increased anti-ssDNA precursor frequency in the presence of NZB T cells. When NZB splenic B cells were co-transferred with DBA/2 T cells, the anti-DNA precursor frequency of the NZB B cells was not reduced. This study demonstrates that T cells can influence the emergency of B cell clones in an Ag-nonspecific manner. The well documented in vivo spontaneous polyclonal activation of NZB B cells may be secondary to T cell-mediated expansion of the B cell repertoire. 相似文献
6.
Comparison of the roles of Ostracods and Cladocerans in regulating community structure and metabolism in freshwater microcosms 总被引:1,自引:1,他引:0
Laboratory microcosms were used to compare the effects of the littoral ostracod Cypridopsis vidua and the planktonic cladoceran Daphnia magna on community structure and metabolism. Filter-feeding by cladocerans, both in the presence and absence of ostracods, greatly
reduced the abundance of planktonic algae when D. magna reached peak density around day 50; rotifers and euglenids were then limited to flocculent matter on the container bottom.
Both net production and community respiration rates decreased as community composition changed. Microcosms containing ostracods
as the only microcrustacean showed little reduction in total algal numbers but the otherwise dominant alga, Scenedesmus spp., was replaced by Ankistrodesmus spp. when peak ostracod density was reached around day 100. Rotifers were completely eliminated but euglenids were able to
coexist with ostracods. Ostracods impacted community metabolism less than cladocerans, but depressed respiration slightly
more than net production. 相似文献
7.
Characterization of a progressive neurodegenerative disease induced by a temperature-sensitive Moloney murine leukemia virus infection. 总被引:10,自引:5,他引:5 下载免费PDF全文
A progressive neurodegenerative disease occurred following infection of mice with a temperature-sensitive (ts) isolate of Moloney (Mo) murine leukemia virus (MuLV), ts Mo BA-1 MuLV. This NB-tropic ecotropic MuLV, which was ts for a late function, induced a syndrome of tremor, weakness of the hind limbs, and spasticity following infection of several strains of laboratory neonatal mice, including NFS, C3H/He, CBA, SJL, and BALB/c. The latent period of 8 to 16 weeks was considerably longer than that observed for the acute paralytic diseases observed following neonatal infection with other ts Mo-MuLV, rat-passaged Friend MuLV, and some wild mouse ecotropic MuLVs. Spongiform pathology without inflammation and degeneration of neurons devoid of budding virions occurred in the cerebellar grey matter, brain stem, and upper spinal cord; but lower spinal cord anterior horn cells were less obviously affected than in other MuLV-associated neuroparalytic syndromes. ts Mo BA-1 MuLV differed from other ts Mo-MuLV mutants that are capable of inducing a neuroparalytic syndrome in that while infected nervous system tissue contained high levels of MuLV p30 and gp70, no evidence of precursor accumulation or abnormal processing of MuLV p30 or gp70 could be demonstrated. The localization of virus within the nervous system suggests that direct neuronal infection may not be the etiologic mechanism in this MuLV-induced neurodegenerative disease. 相似文献
8.
We continuously weighed fully distended excised or in situ canine lobes to estimate the fluid filtration coefficient (Kf) of the arterial and venous extra-alveolar vessels compared with that of the entire pulmonary circulation. Alveolar pressure was held constant at 25 cmH2O after full inflation. In the in situ lobes, the bronchial circulation was interrupted by embolization. Kf was estimated by two methods (Drake and Goldberg). Extra-alveolar vessels were isolated from alveolar vessels by embolizing enough 37- to 74-micron polystyrene beads into the lobar artery or vein to completely stop flow. In excised lobes, Kf's of the entire pulmonary circulation by the Drake and Goldberg methods were 0.122 +/- 0.041 (mean +/- SD) and 0.210 +/- 0.080 ml X min-1 X mmHg-1 X 100 g lung-1, respectively. Embolization was not found to increase the Kf's. The mean Kf's of the arterial extra-alveolar vessels were 0.068 +/- 0.014 (Drake) and 0.069 +/- 0.014 (Goldberg) (24 and 33% of the Kf's for the total pulmonary circulation). The mean Kf's of the venous extra-alveolar vessels were similar [0.046 +/- 0.020 (Drake) and 0.065 +/- 0.036 (Goldberg) or 33 and 35% of the Kf's for the total circulation]. No significant difference was found between the extra-alveolar vessel Kf's of in situ vs. excised lobes. These results suggest that when alveolar pressure, lung volume, and pulmonary vascular pressures are high, approximately one-third of the total fluid filtration comes from each of the three compartments. 相似文献
9.
Coypu insulin. Primary structure, conformation and biological properties of a hystricomorph rodent insulin. 总被引:2,自引:0,他引:2 下载免费PDF全文
M Bajaj T L Blundell R Horuk J E Pitts S P Wood L K Gowan C Schwabe A Wollmer J Gliemann S Gammeltoft 《The Biochemical journal》1986,238(2):345-351
Insulin from a hystricomorph rodent, coypu (Myocaster coypus), was isolated and purified to near homogeneity. Like the other insulins that have been characterized in this Suborder of Rodentia, coypu insulin also exhibits a very low (3%) biological potency, relative to pig insulin, on lipogenesis in isolated rat fat-cells. The receptor-binding affinity is significantly higher (5-8%) in rat fat-cells, in rat liver plasma membranes and in pig liver cells, indicating that the efficacy of coypu insulin on receptors is about 2-fold lower than that of pig insulin. The primary structures of the oxidized A- and B-chains were determined, and our sequence analysis confirms a previous report [Smith (1972) Diabetes 21, Suppl. 2, 457-460] that the C-terminus of the A-chain is extended by a single residue (i.e. aspartate-A22), in contrast with most other insulin sequences, which terminate at residue A21. In spite of a large number of amino acid substitutions (relative to mammalian insulins), computer-graphics model-building studies suggest a similar spatial arrangement for coypu insulin to that for pig insulin. The substitution of the zinc-co-ordinating site (B10-His----Gln) along with various substitutions on the intermolecular surfaces involved in the formation of higher aggregates are consistent with the observation that this insulin is predominantly 'monomeric' in nature. The c.d. spectrum of coypu insulin is relatively similar to those of casiragua insulin and of bovine insulin at low concentration. 相似文献
10.
A new method for the purification of gap junctions is described which depends on the extraction of cell monolayers or tissue homogenates with Triton X-100. The major band on SDS-polyacrylamide gel electrophoresis (PAGE) of junctional preparations from a variety of vertebrate sources has an apparent mol. wt. of 16,000 (16 K). Further evidence for the junctional origin of the 16 K protein is provided by the results of four different experimental approaches. (i) The junctions form a sharp band in potassium iodide density gradients at 1.195 g/cm3 and the 16 K protein is the only detectable band in fractions of this bouyant density. (ii) The junctions are progressively solubilised by increasing concentrations of SDS (in the range 0.1-0.5%) and the dissolution of the junctional structure, observed by electron microscopy, parallels the release of the 16 K protein. (iii) Glutaraldehyde fixation of intact junctions cross-links the 16 K protein. (iv) The recoverable amount of the 16 K protein correlates with known changes in gap junctional area in the regenerating weanling rat liver after partial hepatectomy and in V79 cell cultures exposed to 4beta-phorbol 12-myristate 13-acetate. 相似文献