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51.
In addition to its central role in blood coagulation and hemostasis, human alpha-thrombin is a growth factor for a variety of cell types. We recently demonstrated that interferon-gamma (IFNgamma)-differentiated U937 cells show increased expression of the proteolytically activated receptor for thrombin (PAR-1) relative to undifferentiated U937. In the present study we show that cell proliferation is inhibited in IFNgamma-differentiated cells relative to undifferentiated U937. Addition of thrombin to the differentiated cells, however, overcomes the inhibition and restores the cells to a highly proliferative state. Ribonuclease protection assays indicate that the IFNgamma-induced growth arrest is associated with an increased expression of the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) and downregulation of cyclin D(1). Treatment of cells with thrombin downregulates p21(CIP1/WAF1) expression in these cells and upregulates cyclin D(1) mRNA expression, thus overcoming the differentiation-related effects in a coordinated manner. Treating differentiated cells with the PAR-1 activation peptide, SFLLRN, stimulates proliferation and has effects similar to those of thrombin on expression of p21(CIP1/WAF1). Thus, it appears that these thrombin stimulated proliferative effects are mediated through activation of PAR-1. These results may help explain how thrombin can overcome growth arrest in normal tissue to initiate tissue repair and why thrombin and thrombin-like enzymes may contribute to unrestricted proliferation observed in certain malignancies. 相似文献
52.
In this paper, we investigate how the level of diversity amongst individual neural networks in a bagged ensemble can significantly influence overall ensemble generalization performance. We propose a new technique that tunes this diversity so that ensemble generalization performance is optimized and evaluate its performance on benchmark regression data-sets. 相似文献
53.
Rod and cone photoreceptors project from the outer retinal surface into a
carbohydrate-rich interphotoreceptor matrix (IPM). Unique IPM
glycoconjugates are distributed around rods and cones. Wheat germ
agglutinin (WGA) strongly decorates the rod matrix domains and weakly
decorates the cone matrix domains. This study characterizes the major
WGA-binding glycoprotein in the human IPM, which we refer to as SPACR
(sialoprotein associated with cones and rods). SPACR, which has a molecular
weight of 147 kDa, was isolated and purified from the IPM by lectin
affinity chromatography. A polyclonal antibody to SPACR was prepared that
colocalizes in tissue preparations with WGA-binding domains in the IPM.
Sequential digestion of SPACR with N- and O- glycosidases results in a
systematic increase in electrophorectic mobility, indicating the presence
of both N- and O-linked glycoconjugates. Complete deglycosylation results
in a reduction in the relative molecular mass of SPACR by about 30%.
Analysis of lectin binding allowed us to identify some of the structural
characteristics of SPACR glycoconjugates. Treatment with neuraminidase
exposes Galbeta1- 3GalNAc disaccharide as indicated by positive peanut
agglutinin (PNA) staining, accompanied by the loss of WGA staining. Maackia
amurensis agglutinins (MAA-1 and MAA-2), specific for sialic acid in
alpha2-3 linkage to Gal, bind SPACR, while Sambucus nigra agglutinin (SNA),
specific for alpha2-6 linked sialic acid, does not, indicating that the
dominant glycoconjugate determinant on SPACR is the O-linked carbohydrate,
NeuAcalpha2-3Galbeta1-3GalNAc. The abundance of sialic acid in SPACR
suggests that this glycoprotein may contribute substantially to the
polyanionic nature of the IPM. The carbohydrate chains present on SPACR
could also provide sites for extensive crosslinking and participate in the
formation of the ordered IPM lattice that surrounds the elongate
photoreceptors projecting from the outer retinal surface.
相似文献
54.
Tamas David-Barrett Anna Rotkirch James Carney Isabel Behncke Izquierdo Jaimie A. Krems Dylan Townley Elinor McDaniell Anna Byrne-Smith Robin I. M. Dunbar 《PloS one》2015,10(3)
The ability to create lasting, trust-based friendships makes it possible for humans to form large and coherent groups. The recent literature on the evolution of sociality and on the network dynamics of human societies suggests that large human groups have a layered structure generated by emotionally supported social relationships. There are also gender differences in adult social style which may involve different trade-offs between the quantity and quality of friendships. Although many have suggested that females tend to focus on intimate relations with a few other females, while males build larger, more hierarchical coalitions, the existence of such gender differences is disputed and data from adults is scarce. Here, we present cross-cultural evidence for gender differences in the preference for close friendships. We use a sample of ∼112,000 profile pictures from nine world regions posted on a popular social networking site to show that, in self-selected displays of social relationships, women favour dyadic relations, whereas men favour larger, all-male cliques. These apparently different solutions to quality-quantity trade-offs suggest a universal and fundamental difference in the function of close friendships for the two sexes. 相似文献
55.
每搏量变异度是动态的容量监测指标.机械通气患者心肺的相互作用是每搏量变异度的产生基础,通过动脉压力波形分析技术可以进行连续监测.每搏量变异度能够准确预测容量治疗反应,与静态的血流动力学参数相比,对于优化心输出量和组织氧供更有优势,但也存在一定的局限性.每搏量变异度受多种因素影响且不能用于自主呼吸和心律失常的患者.临床应用时应该综合考虑其影响因素,结合其他的指标和方法指导容量治疗. 相似文献
56.
Human infections with subtype H7 avian influenza viruses have been reported as early as 1979. In 1996, a genetically stable 24-nucleotide deletion emerged in North American H7 influenza virus hemagglutinins, resulting in an eight amino acid deletion in the receptor-binding site. The continuous circulation of these viruses in live bird markets, as well as its documented ability to infect humans, raises the question of how these viruses achieve structural stability and functionality. Here we report a detailed molecular analysis of the receptor binding site of the North American lineage subtype H7N2 virus A/New York/107/2003 (NY107), including complexes with an avian receptor analog (3′-sialyl-N-acetyllactosamine, 3′SLN) and two human receptor analogs (6′-sialyl-N-acetyllactosamine, 6′SLN; sialyllacto-N-tetraose b, LSTb). Structural results suggest a novel mechanism by which residues Arg220 and Arg229 (H3 numbering) are used to compensate for the deletion of the 220-loop and form interactions with the receptor analogs. Glycan microarray results reveal that NY107 maintains an avian-type (α2-3) receptor binding profile, with only moderate binding to human-type (α2-6) receptor. Thus despite its dramatically altered receptor binding site, this HA maintains functionality and confirms a need for continued influenza virus surveillance of avian and other animal reservoirs to define their zoonotic potential. 相似文献
57.
58.
59.
The utility of the decimal growth stage (DGS) scoring system for cereals is reviewed. The DGS is the most widely used scale in academic and commercial applications because of its comprehensive coverage of cereal developmental stages, the ease of use and definition provided and adoption by official agencies. The DGS has demonstrable and established value in helping to optimise the timing of agronomic inputs, particularly with regard to plant growth regulators, herbicides, fungicides and soluble nitrogen fertilisers. In addition, the DGS is used to help parameterise crop models, and also in understanding the response and adaptation of crops to the environment. The value of the DGS for increasing precision relies on it indicating, to some degree, the various stages in the development of the stem apex and spike. Coincidence of specific growth stage scores with the transition of the apical meristem from a vegetative to a reproductive state, and also with the period of meiosis, is unreliable. Nonetheless, in pot experiments it is shown that the broad period of booting (DGS 41–49) appears adequate for covering the duration when the vulnerability of meiosis to drought and heat stress is exposed. Similarly, the duration of anthesis (61–69) is particularly susceptible to abiotic stresses: initially from a fertility perspective, but increasingly from a mean grain weight perspective as flowering progresses to DGS 69 and then milk development. These associations with DGS can have value at the crop level of organisation: for interpreting environmental effects, and in crop modelling. However, genetic, biochemical and physiological analysis to develop greater understanding of stress acclimation during the vegetative state, and tolerance at meiosis, does require more precision than DGS can provide. Similarly, individual floret analysis is needed to further understand the genetic basis of stress tolerance during anthesis. 相似文献
60.
Patrick Carney Steven Lopez Amanda Mickley Kirill Grinberg Wenyao Zhang Zhaohua Dai 《Chirality》2011,23(10):916-920
Two multimode Hg(II) sensors, L‐MethBQA and L‐CysBQA, were obtained by fusing methionine or S‐methyl cysteine, into a bis‐quinolyl amine‐based chiral podand scaffold. Quinolyl groups serve as the fluorophore and possess nitrogen lone pairs capable of chelating metal ions. On exposure to Hg2+ or Zn2+, these sensors show signal enhancement in fluorescence. However, Cu2+ quenches their fluorescence in 30:70 acetontrile/water. L‐CysBQA complexes with Hg2+, producing an exciton‐coupled circular dichroism spectrum with the opposite sign to the one that is produced by Cu2+ or Zn2+ complexation. L‐CysBQA binds Hg2+ more strongly than Zn2+ and is shown to differentiate Hg2+ from other metal ions, such as Zn2+, Cu2+, Ni2+, and Pb2+, exceptionally well. The synergistic use of relatively soft sulfur, quinoline‐based chiral ligands and chiroptically enhanced fluorescence detection results in high sensitivity and selectivity for Hg2+. Chirality, 2011. © 2011 Wiley‐Liss, Inc. 相似文献