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11.
Thyroid cancer after Chernobyl. 总被引:17,自引:0,他引:17
12.
To validate procedures of rational drug design, it is important to develop computational methods that predict binding sites between a protein and a ligand molecule. Many small molecules have been tested using such programs, but examination of protein-protein and peptide-protein interactions has been sparse. We were able to test such applications once the structures of both the maltose-binding protein (MBP) and the ligand-binding domain of the aspartate receptor, which binds MBP, became available. Here we predict the binding site of MBP to its receptor using a 'binary docking' technique in which two MBP octapeptide sequences containing mutations that eliminate maltose chemotaxis are independently docked to the receptor. The peptides in the docked solutions superimpose on their original positions in the structure of MBP and allow the formation of an MBP-receptor complex. The consistency of the computational and biological results supports this approach for predicting protein-protein and peptide-protein interactions. 相似文献
13.
Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. 总被引:149,自引:0,他引:149
M M Shull I Ormsby A B Kier S Pawlowski R J Diebold M Yin R Allen C Sidman G Proetzel D Calvin 《Nature》1992,359(6397):693-699
Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions. 相似文献
14.
Rui M Costa Nikolai B Federov Jeff H Kogan Geoffrey G Murphy Joel Stern Masuo Ohno Raju Kucherlapati Tyler Jacks Alcino J Silva 《Nature》2002,415(6871):526-530
Neurofibromatosis type I (NF1) is one of the most common single-gene disorders that causes learning deficits in humans. Mice carrying a heterozygous null mutation of the Nfl gene (Nfl(+/-) show important features of the learning deficits associated with NF1 (ref. 2). Although neurofibromin has several known properties and functions, including Ras GTPase-activating protein activity, adenylyl cyclase modulation and microtubule binding, it is unclear which of these are essential for learning in mice and humans. Here we show that the learning deficits of Nf1(+/-) mice can be rescued by genetic and pharmacological manipulations that decrease Ras function. We also show that the Nf1(+/-) mice have increased GABA (gamma-amino butyric acid)-mediated inhibition and specific deficits in long-term potentiation, both of which can be reversed by decreasing Ras function. Our results indicate that the learning deficits associated with NF1 may be caused by excessive Ras activity, which leads to impairments in long-term potentiation caused by increased GABA-mediated inhibition. Our findings have implications for the development of treatments for learning deficits associated with NF1. 相似文献
15.
Summary Immunohistochemistry revealed an Ig-A-like substance on the luminal surface of the pineal follicles and in the parafollicular layer. This substance was observed around 1 week of age and disappeared by 8 weeks at the time when the transformation of the follicular pattern leads to an adult-type pineal tissue. 相似文献
16.
K K Leong K M Yu W B Lee 《厦门大学学报(自然科学版)》2002,(Z1)
Product data management (PDM) has been accepted as an important tool for the manufacturing industries. In recent years, more and mor e researches have been conducted in the development of PDM. Their research area s include system design, integration of object-oriented technology, data distri bution, collaborative and distributed manufacturing working environment, secur ity, and web-based integration. However, there are limitations on their rese arches. In particular, they cannot cater for PDM in dis... 相似文献
17.
D Ashall B Parkinson 《厦门大学学报(自然科学版)》2002,(Z1)
Background: During the last fifteen years there ha s been an increased drive for organisations to reduce costs. From a production po int, this has often centred on lean manufacturing and JIT waste elimination proc esses. However, in 1991, the Iaccocca Institute Bethlehem P.A commissioned a re port specifically to analyse the changing nature of the marketplace. As a result , in the following year, the Agile Manufacturing Forum was initiated and the ter m ‘agile or responsive manufacturing‘ was first intr... 相似文献
18.
19.
Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition 总被引:2,自引:0,他引:2
K. Brune W. S. Beck G. Geisslinger S. Menzel-Soglowek B. M. Peskar B. A. Peskar 《Cellular and molecular life sciences : CMLS》1991,47(3):257-261
Summary Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics. 相似文献
20.