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41.
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
42.
Short alanine peptides, containing 16 or 17 residues, appear to form alpha-helices in aqueous solution. But the main spectroscopic analyses used on helical peptides (circular dichroism and nuclear magnetic resonance) cannot distinguish between an alpha-helix (in which the ith residue is hydrogen-bonded to residue i + 4; ref. 9) and the next most common peptide helix, the 3(10)-helix10 (i-->i + 3 hydrogen-bonding). To address this problem we have designed single and doubly spin-labelled analogues of alanine-based peptides in which the nitroxide spin label forms an unbranched side chain extending from the sulphur atom of a cysteine residue. Here we report the circular dichroism, Fourier-transform infrared and electron-spin resonance spectra of these peptides under helix-forming conditions. The infrared absorbance gives an amide I' band with a frequency that is substantially different from that observed for alpha-helices. The electron-spin resonance spectra of doubly labelled helices show that the ranking of distances between side chains, around a single turn (residues 4-8), is inconsistent with an alpha-helical structure. Our experiments suggest that the more likely peptide geometry is a 3(10)-helix. 相似文献
43.
The failing heart. 总被引:19,自引:0,他引:19
Cardiomyopathies are disorders affecting heart muscle that usually result in inadequate pumping of the heart. They are the most common cause of heart failure and each year kill more than 10,000 people in the United States. In recent years, there have been breakthroughs in understanding the molecular mechanisms involved in this group of conditions, with knowledge of the genetic basis for cardiomyopathies perhaps seeing the largest advance, enabling clinicians to devise improved diagnostic strategies and preparing the stage for new therapies. 相似文献
44.
N. Ait-Langomazino R. Sellier G. Jouquet M. Trescinski 《Cellular and molecular life sciences : CMLS》1991,47(6):533-539
Summary A blown bitumen Mexphalte R 90/40 with a high content of saturated hydrocarbons was degraded by several microorganisms to the same extent. In batch cultures ofSaccharomycopsis lipolytica, maximal biodegradation was estimated to be about 9% w/w, 3.2·10–3 g/cm2 and 3.1·10–3 cm of degraded bitumen. The Mexphalte R 90/40 degradation rate was closely coupled to biofilm formation. The microbial activity concerned predominantly the oxidation of saturated hydrocarbons. A direct distillation bitumen 80/100 with a low content of saturated hydrocarbons and a high content of aromatic hydrocarbons and resins was more resistant to biodegradation. 相似文献
45.
Heat-shock proteins are normal constituents of cells whose synthesis is increased on exposure to various forms of stress. They are interesting because of their ubiquity and high conservation during evolution. Two families of heat-shock proteins, hsp60s and hsp70s, have been implicated in accelerating protein folding and oligomerization and also in maintaining proteins in an unfolded state, thus facilitating membrane transport. The Escherichia coli hsp70 analogue, DnaK, and two other heat-shock proteins, DnaJ and GrpE, are required for cell viability at high temperatures and are involved in DNA replication of phage lambda and plasmids P1 and F. These three proteins are involved in replication in vitro of P1 DNA along with many host replication proteins and the P1 RepA initiator protein. RepA exists in a stable protein complex with DnaJ containing a dimer each of RepA and DnaJ. We report here that DnaK and DnaJ mediate an alteration in the P1 initiator protein, rendering it much more active for oriP1 DNA binding. 相似文献
46.
J. S. Frankel 《Cellular and molecular life sciences : CMLS》1982,38(6):673-674
Summary The tissue specificity of lactate dehydrogenase (EC 1.1.1.27) in brain and eye of the teleostPhallichthys amates was examined by acrylamide gel electrophoresis. It is suggested that subunit association is a function of gene product accessibility superimposed upon genetic restriction of assembly. 相似文献
47.
Summary Host cell reactivation capacity for ozone T3 phage was determined for differentE. coli strains deficient in one or more of the DNA repair mechanisms. The results indicate that DNA polymerase I appears to play a key role in the repair of damage produced on the DNA by ozone while thelexA gene product seems to play a minor one.This research was sponsored by the National Sciences and Engineering Council of Canada. One of us (PLH) acknowledges a scholarship from the NSERCof Canada. 相似文献
48.
During the evolution of proteins the pressure to optimize biological activity is moderated by a need for efficient folding. For most proteins, this is accomplished through spontaneous folding to a thermodynamically stable and active native state. However, in the extracellular bacterial alpha-lytic protease (alphaLP) these two processes have become decoupled. The native state of alphaLP is thermodynamically unstable, and when denatured, requires millennia (t1/2 approximately 1,800 years) to refold. Folding is made possible by an attached folding catalyst, the pro-region, which is degraded on completion of folding, leaving alphaLP trapped in its native state by a large kinetic unfolding barrier (t1/2 approximately 1.2 years). alphaLP faces two very different folding landscapes: one in the presence of the pro-region controlling folding, and one in its absence restricting unfolding. Here we demonstrate that this separation of folding and unfolding pathways has removed constraints placed on the folding of thermodynamically stable proteins, and allowed the evolution of a native state having markedly reduced dynamic fluctuations. This, in turn, has led to a significant extension of the functional lifetime of alphaLP by the optimal suppression of proteolytic sensitivity. 相似文献
49.
We discuss a generalization of the standard notion of probability space and show that the emerging framework, to be called operational probability theory, can be considered as underlying quantal theories. The proposed framework makes special reference to the convex structure of states and to a family of observables which is wider than the familiar set of random variables: it appears as an alternative to the known algebraic approach to quantum probability. 相似文献
50.
A. E. Yassen H. A. Hassan L. S. Kawashti 《Cellular and molecular life sciences : CMLS》1994,50(11-12):1111-1114
A detailed karyotypic analysis of two Egyptian species of bats,Taphozous perforatus andTaphozous nudiventris, was made on the basis of conventional data and G-band patterns. No detectable karyotypic difference was found between the two species (2n=42, F.N. 64). By comparison of G-band patterns, some differences between the two species were seen in the corresponding autosomal pairs. These results are reported for the first time in Egypt. 相似文献