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361.
Expression of human proteoglycan in Chinese hamster ovary cells inhibits cell proliferation 总被引:22,自引:0,他引:22
In studying the functional role of an extracellular matrix proteoglycan, decorin, we have made observations that suggest a role for this proteoglycan in the control of cell proliferation. Extracellular matrices are made up of different combinations of collagens, elastin, hyaluronic acid, proteoglycans and various glycoproteins such as fibronectin. Most of these components can interact with cells, and much of the control of cell adhesion, migration and differentiation appears to be mediated by these interactions. Earlier studies have also attributed growth-regulatory activities to intact extracellular matrices, but the individual molecules responsible for these effects have not been characterized. We report here that Chinese hamster ovary (CHO) cell lines expressing human decorin from a stably transfected complementary DNA construct form a more orderly monolayer and grow to a lower saturation density than control cells lacking decorin. The extent of the morphological changes correlates with the level of decorin expression, and the saturation density is inversely proportional to it. The reduction in the saturation densities of the cell lines with the highest expression of decorin is more than 50%. These results reveal a novel growth inhibitory mechanism which may be related to contact inhibition of cell proliferation. 相似文献
362.
B E Saether 《Nature》1988,331(6157):616-617
A large amount of variation is found in most reproductive traits of birds. Clutch size for instance, can vary from 1 to 15 between species of similar body weight. The adaptive significance of this variation is only poorly understood. According to life-history theory, large clutch size and early onset of reproduction are expected when the chances of survival are low. There is some support for the existence of such a relationship from studies of single species. Here I present evidence that, in European birds, clutch size is increased, and onset of reproduction occurs earlier in life, when the probability of survival is low. 相似文献
363.
Noradrenaline (NA) regulates arterial smooth muscle tone and hence blood vessel diameter and blood flow. NA apparently increases tone by causing a calcium influx through the cell membrane. Two calcium influx pathways have been proposed: voltage-activated calcium channels and NA-activated calcium-permeable channels that are voltage-insensitive. Although voltage-activated calcium channels have been identified in arterial smooth muscle, voltage-insensitive calcium channels activated by NA have not. We show here that NA contractions of rabbit mesenteric arteries increase with depolarization. The increase parallels the elevation of open-state probability (P0) of single, voltage-dependent calcium channels. The action of noradrenaline can be explained by NA-activating voltage-dependent calcium channels, rather than by opening a second type of channel. We show directly that NA increases the open-state probability of single calcium channels. Thus, in the presence of NA, calcium entry through voltage-dependent calcium channels can regulate smooth muscle tone at physiological membrane potentials. These results may have relevance to pathophysiological conditions such as hypertension. 相似文献
364.
汽轮发电机端部似稳涡流场数学模型 总被引:4,自引:0,他引:4
导出了描述发是端部涡流场的边值问题,并讨论了此问题的确定性。导出了与此边值问题等价的条件变化问题,并给出了三维行波场下变分式的具体形式。对QFS-300-2型汽轮发电机的端部场作了实例计算,计算结果与测试结果是一致的,证实了本文所提出的数学模型的正确性。 相似文献
365.
Suppression of in vitro haematopoiesis following human immunodeficiency virus infection 总被引:2,自引:0,他引:2
Viral infections are frequently associated with haematological disorders. Abnormalities including leukopenia, anaemia and thrombocytopenia are commonly observed in patients with the acquired immune deficiency syndrome (AIDS) or the AIDS-related complex (ARC). The underlying cause of these haematological abnormalities is poorly understood. We report here that bone marrow progenitors isolated from AIDS or ARC patients are responsive to recombinant human granulocyte-macrophage colony stimulating factor (rGM-CSF) and recombinant erythropoietin. Antibodies present in the serum of patients infected with the human immunodeficiency virus (HIV), however, could suppress the growth of these progenitors, but not the growth of progenitors from HIV seronegative controls. A component of this immune-mediated suppression appears to be antibodies directed towards the envelope glycoprotein (gp120) of HIV. 相似文献
366.
N E Simpson K K Kidd P J Goodfellow H McDermid S Myers J R Kidd C E Jackson A M Duncan L A Farrer K Brasch 《Nature》1987,328(6130):528-530
Multiple endocrine neoplasis type 2A (MEN2A) is one of several kinds of cancers that appear to be inherited in an autosomally dominant fashion. We have assigned the MEN2A locus to chromosome 10 by linkage with a new DNA marker (D10S5). The linkage led us to investigate other chromosome 10 markers and demonstrate linkage between the disease locus and the interstitial retinol-binding protein (IRBP) gene. The D10S5 locus was sublocalized to 10q21.1 by hybridization in situ and the IRBP gene to p11.2----q11.2 with a secondary site at q24----q25. The linkages were established using 292 members of five families, three different restriction fragment length polymorphisms (RFLPs) at D10S5 and two RFLPs recognized by the IRBP probe. The recombination frequencies from pairwise linkage analysis between the disease and two marker loci D10S5 and IRBP were 0.19 and 0.11, with maximum lod scores of 3.6 and 8.0 respectively. Ordering of the three loci by multipoint analysis placed the IRBP gene approximately midway between the disease and D10S5 loci. 相似文献
367.
The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid beta-protein gene 总被引:1,自引:0,他引:1
R E Tanzi P H St George-Hyslop J L Haines R J Polinsky L Nee J F Foncin R L Neve A I McClatchey P M Conneally J F Gusella 《Nature》1987,329(6135):156-157
Amyloid beta-protein (AP) is a peptide of relative molecular mass (Mr) 42,000 found in the senile plaques, cerebrovascular amyloid deposits, and neurofibrillary tangles of patients with Alzheimer's disease and Down's syndrome (trisomy 21). Recent molecular genetic evidence has indicated that AP is encoded as part of a larger protein by a gene on chromosome 21 (refs 5-7). The defect in the inherited autosomal dominant form of Alzheimer's disease, familial Alzheimer's disease (FAD), has been mapped to the same approximate region of chromosome 21 by genetic linkage to anonymous DNA markers, raising the possibility that this gene product, which could be important in the pathogenesis of Alzheimer's disease, is also the site of the inherited defect in FAD (ref. 5). We have determined the pattern of segregation of the AP gene in FAD pedigrees using restriction fragment length polymorphisms. The detection of several recombination events with FAD suggests that the AP gene is not the site of the inherited defect underlying this disorder. 相似文献
368.
The expression of hybrid HIV:Ty virus-like particles in yeast 总被引:3,自引:0,他引:3
369.
Y Y Toyoshima S J Kron E M McNally K R Niebling C Toyoshima J A Spudich 《Nature》1987,328(6130):536-539
The rotating crossbridge model for muscle contraction proposes that force is produced by a change in angle of the crossbridge between the overlapping thick and thin filaments. Myosin, the major component of the thick filament, is comprised of two heavy chains and two pairs of light chains. Together they form two globular heads, which give rise to the crossbridge in muscle, and a coiled-coil rod, which forms the shaft of the thick filament. The isolated head fragment, subfragment-1 (S1), contains the ATPase and actin-binding activities of myosin (Fig. 1). Although S1 seems to have the requisite enzymatic activity, direct evidence that S1 is sufficient to drive actin movement has been lacking. It has long been recognized that in vitro movement assays are an important approach for identifying the elements in muscle responsible for force generation. Hynes et al. showed that beads coated with heavy meromyosin (HMM), a soluble proteolytic fragment of myosin consisting of a part of the rod and the two heads, can move on Nitella actin filaments. Using the myosin-coated surface assay of Kron and Spudich, Harada et al. showed that single-headed myosin filaments bound to glass support movement of actin at nearly the same speed as intact myosin filaments. These studies show that the terminal portion of the rod and the two-headed nature of myosin are not required for movement. To restrict the region responsible for movement further, we have modified the myosin-coated surface assay by replacing the glass surface with a nitrocellulose film. Here we report that myosin filaments, soluble myosin, HMM or S1, when bound to a nitrocellulose film, support actin sliding movement (Fig. 2). That S1 is sufficient to cause sliding movement of actin filaments in vitro gives strong support to models of contraction that place the site of active movement in muscle within the myosin head. 相似文献
370.
R A Dixon I S Sigal E Rands R B Register M R Candelore A D Blake C D Strader 《Nature》1987,326(6108):73-77
Recently the genes for several hormone receptors that interact with guanine nucleotide binding proteins (G proteins) have been cloned, including the hamster beta 2-adrenergic receptor (beta 2AR), a human beta AR, the turkey erythrocyte beta AR and the porcine muscarinic acetylcholine receptor (MAR). All these receptors share some amino-acid homology with rhodopsin, particularly in 7 hydrophobic stretches of residues that are believed to represent transmembrane helices. To determine whether differences in ligand specificity result from the divergence in the sequences of the hydrophilic regions of these receptors, we have expressed in mammalian cells genes for the wild-type hamster and human beta AR proteins, and a series of deletion mutant genes of the hamster beta 2AR. The pharmacology of the expressed receptors indicates that most of the hydrophilic residues are not directly involved in the binding of agonists or antagonists to the receptor. In addition, we have identified a mutant receptor that has high agonist affinity but does not couple to adenylate cyclase. 相似文献