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1.
Wendy A. Douglass Robert H. Hyland Christopher D. Buckley Aymen Al-Shamkhani Jacqueline M. Shaw Sarah L. Scarth David L. Simmons S.K.Alex Law 《FEBS letters》1998,440(3):125
The cysteine-rich region (CRR) of the β2 integrin subunit was replaced by that of β1 to give the chimera β2NV1. β2NV1 can combine with αL to form a variant leukocyte-function-associated antigen (LFA)-1 on COS cell surface, suggesting that the specificity of the β2 interaction with αL does not lie in the CRR. Unlike those expressing wild-type LFA-1, COS cells expressing αLβ2NV1 are constitutively active in intercellular adhesion molecule (ICAM)-1 adhesion. These results suggest that activation of LFA-1 involves the release of an intramolecular constraint, which is maintained, in part, by the authentic β2 CRR. 相似文献
2.
Elevated serum gamma-glutamyl transferase (GGT) levels were found in 29% of 155 chronic alcoholics undergoing detoxification treatment. Alkaline phosphatase (AP) was increased in 16%, alanine aminotransferase--SGPT (ALT) in 12% of the patients, while 23% had elevations of either AP or ALT or both. Of the foregoing parameters, GGT was the best single indicator of liver involvement. In course of the follow-ups GGT/ALT correlation improved, but GGT/AP correlation deteriorated. In 9 patients, abstinence during follow-up was associated with progressive decrease in previously elevated serum GGT. Because of its unique sensitivity, GGT may be useful as a screening and/or monitoring aid in alcoholism. 相似文献
3.
Sharat J. Vayttaden Jacqueline Friedman Tuan M. Tran Thomas C. Rich Carmen W. Dessauer Richard B. Clark 《PLoS computational biology》2010,6(1)
We developed a unified model of the GRK-mediated β2 adrenergic receptor (β2AR) regulation that simultaneously accounts for six different biochemical measurements of the system obtained over a wide range of agonist concentrations. Using a single deterministic model we accounted for (1) GRK phosphorylation in response to various full and partial agonists; (2) dephosphorylation of the GRK site on the β2AR; (3) β2AR internalization; (4) recycling of the β2AR post isoproterenol treatment; (5) β2AR desensitization; and (6) β2AR resensitization. Simulations of our model show that plasma membrane dephosphorylation and recycling of the phosphorylated receptor are necessary to adequately account for the measured dephosphorylation kinetics. We further used the model to predict the consequences of (1) modifying rates such as GRK phosphorylation of the receptor, arrestin binding and dissociation from the receptor, and receptor dephosphorylation that should reflect effects of knockdowns and overexpressions of these components; and (2) varying concentration and frequency of agonist stimulation “seen” by the β2AR to better mimic hormonal, neurophysiological and pharmacological stimulations of the β2AR. Exploring the consequences of rapid pulsatile agonist stimulation, we found that although resensitization was rapid, the β2AR system retained the memory of the previous stimuli and desensitized faster and much more strongly in response to subsequent stimuli. The latent memory that we predict is due to slower membrane dephosphorylation, which allows for progressive accumulation of phosphorylated receptor on the surface. This primes the receptor for faster arrestin binding on subsequent agonist activation leading to a greater extent of desensitization. In summary, the model is unique in accounting for the behavior of the β2AR system across multiple types of biochemical measurements using a single set of experimentally constrained parameters. It also provides insight into how the signaling machinery can retain memory of prior stimulation long after near complete resensitization has been achieved. 相似文献
4.
Transmembrane signaling implies that peripheral protein binding to one leaflet be detected by the opposite leaflet. Therefore, protein recruitment into preexisting cholesterol and sphingolipid rich platforms may be required. However, no clear molecular picture has evolved about how these rafts in both leaflets are connected. By using planar lipid bilayers, we show that the peripheral binding of a charged molecule (poly-lysine, PLL) is detected at the other side of the bilayer without involvement of raft lipids. The diffusion coefficient, DP, of PLL differed by a factor of √2 when PLL absorbed to one or to both leaflets of planar membranes. Fluorescence correlation spectroscopy showed that the changes of the lipid diffusion coefficient, DM, were even more pronounced. Although DM remained larger than DP on PLL binding to the first membrane leaflet, DM dropped to DP on PLL binding to both leaflets, which indicated that the lipids sandwiched between two PLL molecules had formed a nanodomain. Due to its small area of ∼20 nm2 membrane electrostriction or leaflet interaction at bilayer midplane can only make a small contribution to interleaflet coupling. The tendency of the system to maximize the area where the membrane is free to undulate seems to be more important. As a spot with increased bending stiffness, the PLL bound patch in one leaflet attracts a stiffening additive on the other leaflet. That is to say, instead of suppressing undulations in two spots, two opposing PLL molecules migrate along a membrane at matching positions and suppress these undulations in a single spot. The gain in undulation energy is larger than the energy required for the alignment of two small PLL domains in opposite leafs and their coordinated diffusion. We propose that this type of mechanical interaction between two membrane separated ligands generally contributes to transmembrane signaling. 相似文献
5.
Ezzatollah Keyhani Jacqueline Keyhani 《Biochimica et Biophysica Acta (BBA)/General Subjects》1980,633(2):211-227
Heme a was not detected either in mitochondria isolated from copper-deficient yeast or in the intact cells. Nevertheless, the intracellular concentration of free porphyrins indicated that the pathway of porphyrin and heme synthesis was not impaired in copper-deficient cells. The immunoprecipitated apo-oxidase from copper-deficient cells revealed an absorption spectrum with maxima at 645, 592, 559, 519 and 423 nm, similar to that of purified porphyrin a. When solubilized mitochondria from [3H]leucine and δ-amino[14C]levulinic acid-labeled copper-deficient yeast cells were incubated with rabbit antiserum against cytochrome c oxidase, a precipitate was obtained. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of this immunoprecipitate showed [3H]leucine associated with six bands and δ-amino[14C]levulinic acid resolved in a single band. HCl fractionation of copper-deficient mitochondria labeled with δ-amino[14C]levulinic acid showed a high specific radioactivity in the fraction extracted by 20% HCl, a solvent which extracts porphyrin a. Thinlayer chromatography of the radioactivity found in 20% HCl showed an RF value identical to that of purified porphyrin a. When δ-amino[3H]levulinic acid-labeled, copper-deficient yeast cells are grown in copper-supplemented medium, the porphyrin a accumulated in copper-deficient cells wa converted into heme a, and this conversion was prevented by cycloheximidine.These observations suggest that porphyrin a is present in the apo-oxidase of copper-deficient cells, but that the conversion to heme a does not occur. This conversion reaction appears to be a point in the biosynthetic pathway of cytochrome c oxidase which is blocked by copper deficieny. 相似文献
6.
W. O. van der Knaap Jacqueline F. N. van Leeuwen Tomasz Goslar Robert Krisai Willy Tinner 《Vegetation History and Archaeobotany》2012,21(1):37-60
Three mires and a small lake in the Swiss and Austrian Alps were studied palynologically at high resolution, covering the
last 1,000, 400, 50 and 1,200 years, respectively. Methodological lessons include: (1) Sub-decadal resolution in upper, little-decomposed
peat layers reveals recurrent marked fluctuations in both percentages and influx of regional tree-pollen types, reflecting
variations in pollen production rather than in plant-population sizes. (2) Intermittent, single-spectrum pollen maxima in
samples of sub-decadal resolution indicate pollen transport in clumps. This type of pollen transport may remain unrecognized
in sections with lower sampling resolution, which may then lead to inappropriate interpretation in terms of plant-population
sizes. (3) The detection of short-lived phases of human impact in decomposed peat requires sampling intervals as close as
0.2 cm. (4) PAR (pollen influx) may reflect vegetation dynamics more faithfully than percentages. Reliable PAR, however, is
difficult to achieve in Alpine mires due to past human impact on peat growth, even when complex depth–age modelling techniques
are used. Critical comparison of PAR with percentages is therefore essential. (5) Careful consideration of spatial scales
in pollen signals (local–regional and subdivisions) is essential for a realistic palaeo-ecological interpretation. Results
in terms of past human impact on vegetation are summarized as follows: (1) Trends in pollen types reflecting regional human
action are in general agreement with earlier findings for the western Swiss Alps, allowing for regional differences. (2) All
mires in the Alps investigated here and in an earlier study experienced human impact during the last millennium. The studied
small lake, lying in sub-alpine pasture, records forest dynamics at a lower elevation since a.d. 800. 相似文献
7.
8.
J. Stuart Horner 《BMJ (Clinical research ed.)》1974,3(5923):100-103
Almost 950,000 of the 21 million passengers passing through London (Heathrow) Airport in 1973 were seen by the health control unit, which is run by the London Borough of Hillingdon. The unit provides 24-hour medical cover and its responsibilities include x-ray examination for tuberculosis and screening passengers from smallpox-infected areas. It is suggested that, in view of changing epidemiological patterns throughout the world, there is a need to modify existing procedures rather than to abandon them. The development of a follow-up system for tracing passengers at risk and improvements in presenting information about health risks to intending travellers are advocated. While such proposals might be opposed, they could be practicable. 相似文献
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10.