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161.
Cell migration refers to a directional cell movement in response to chemoattractant stimulation. In this work, we developed a cell-migration model by mimicking in vivo migration using optically manipulated chemoattractant-loaded microsources. The model facilitates a quantitative characterization of the relationship among the protrusion force, cell motility, and chemoattractant gradient for the first time (to our knowledge). We verified the correctness of the model using migrating leukemia cancer Jurkat cells. The results show that one can achieve the ideal migrating capacity by choosing the appropriate chemoattractant gradient and concentration at the leading edge of the cell.  相似文献   
162.
Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that are activated by growth factor and G-protein-coupled receptors and propagate intracellular signals for growth, survival, proliferation, and metabolism. p85α, a modular protein consisting of five domains, binds and inhibits the enzymatic activity of class IA PI3K catalytic subunits. Here, we describe the structural states of the p85α dimer, based on data from in vivo and in vitro solution characterization. Our in vitro assembly and structural analyses have been enabled by the creation of cysteine-free p85α that is functionally equivalent to native p85α. Analytical ultracentrifugation studies showed that p85α undergoes rapidly reversible monomer-dimer assembly that is highly exothermic in nature. In addition to the documented SH3-PR1 dimerization interaction, we identified a second intermolecular interaction mediated by cSH2 domains at the C-terminal end of the polypeptide. We have demonstrated in vivo concentration-dependent dimerization of p85α using fluorescence fluctuation spectroscopy. Finally, we have defined solution conditions under which the protein is predominantly monomeric or dimeric, providing the basis for small angle x-ray scattering and chemical cross-linking structural analysis of the discrete dimer. These experimental data have been used for the integrative structure determination of the p85α dimer. Our study provides new insight into the structure and assembly of the p85α homodimer and suggests that this protein is a highly dynamic molecule whose conformational flexibility allows it to transiently associate with multiple binding proteins.  相似文献   
163.
The phosphoinositide 3-kinase–Akt signaling pathway is essential to many biological processes, including cell proliferation, survival, metabolism, and angiogenesis, under pathophysiological conditions. Although 3-phosphoinositide–dependent kinase 1 (PDK1) is a primary activator of Akt at the plasma membrane, the optimal activation mechanism remains unclear. We report that adhesion molecule with IgG-like domain 2 (AMIGO2) is a novel scaffold protein that regulates PDK1 membrane localization and Akt activation. Loss of AMIGO2 in endothelial cells (ECs) led to apoptosis and inhibition of angiogenesis with Akt inactivation. Amino acid residues 465–474 in AMIGO2 directly bind to the PDK1 pleckstrin homology domain. A synthetic peptide containing the AMIGO2 465–474 residues abrogated the AMIGO2–PDK1 interaction and Akt activation. Moreover, it effectively suppressed pathological angiogenesis in murine tumor and oxygen-induced retinopathy models. These results demonstrate that AMIGO2 is an important regulator of the PDK1–Akt pathway in ECs and suggest that interference of the PDK1–AMIGO2 interaction might be a novel pharmaceutical target for designing an Akt pathway inhibitor.  相似文献   
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166.
Stripe rust is a devastating fungal disease of wheat caused by Puccinia striiformis f. sp tritici (Pst). The WHEAT KINASE START1 (WKS1) resistance gene has an unusual combination of serine/threonine kinase and START lipid binding domains and confers partial resistance to Pst. Here, we show that wheat (Triticum aestivum) plants transformed with the complete WKS1 (variant WKS1.1) are resistant to Pst, whereas those transformed with an alternative splice variant with a truncated START domain (WKS1.2) are susceptible. WKS1.1 and WKS1.2 preferentially bind to the same lipids (phosphatidic acid and phosphatidylinositol phosphates) but differ in their protein-protein interactions. WKS1.1 is targeted to the chloroplast where it phosphorylates the thylakoid-associated ascorbate peroxidase (tAPX) and reduces its ability to detoxify peroxides. Increased expression of WKS1.1 in transgenic wheat accelerates leaf senescence in the absence of Pst. Based on these results, we propose that the phosphorylation of tAPX by WKS1.1 reduces the ability of the cells to detoxify reactive oxygen species and contributes to cell death. This response takes several days longer than typical hypersensitive cell death responses, thus allowing the limited pathogen growth and restricted sporulation that is characteristic of the WKS1 partial resistance response to Pst.  相似文献   
167.
Adipose tissue is a structure highly specialized in energy storage. The adipocyte is the parenchymal component of adipose tissue and is known to be mesoderm or neuroectoderm in origin; however, adipocyte development remains poorly understood. Here, we investigated the development of adipose tissue by analyzing postnatal epididymal adipose tissue (EAT) in mouse. EAT was found to be generated from non-adipose structure during the first 14 postnatal days. From postnatal day 1 (P1) to P4, EAT is composed of multipotent progenitor cells that lack adipogenic differentiation capacity in vitro, and can be regarded as being in the 'undetermined' state. However, the progenitor cells isolated from P4 EAT obtain their adipogenic differentiation capacity by physical interaction generated by cell-to-matrix and cell-to-cell contact both in vitro and in vivo. In addition, we show that impaired angiogenesis caused by either VEGFA blockade or macrophage depletion in postnatal mice interferes with adipose tissue development. We conclude that appropriate interaction between the cellular and matrix components along with proper angiogenesis are mandatory for the development of adipose tissue.  相似文献   
168.
The resolution of chiral compound‐forming systems using hybrid processes was discussed recently. The concept is of large relevance as these systems form the majority of chiral substances. In this study, a novel hybrid process is presented, which combines pertraction and subsequent preferential crystallization and is applicable for the resolution of such systems. A supported liquid membrane applied in a pertraction process provides enantiomeric enrichment. This membrane contains a solution of a chiral compound acting as a selective carrier for one of the enantiomers. Screening of a large number of liquid membranes and potential carriers using the conductor‐like screening model for realistic solvation method led to the identification of several promising carriers, which were tested experimentally in several pertraction runs aiming to yield enriched (+)‐(S)‐mandelic acid (MA) solutions from racemic feed solutions. The most promising system consisted of tetrahydronaphthalene as liquid membrane and hydroquinine‐4‐methyl‐2‐quinolylether (HMQ) as chiral carrier achieving enantiomeric excesses of 15% in average. The successful production of (+)‐(S)‐MA with a purity above 96% from enriched solutions by subsequent preferential crystallization proved the applicability of the hybrid process. Chirality, 2011. © 2010 Wiley‐Liss, Inc.  相似文献   
169.
Yang H  Wang K  Song X  Xu F 《Bioresource technology》2011,102(14):7171-7176
Xylooligosaccharides (XOS) with DP 2-4 are important synbiotics used as food ingredients based on its prebiotic characteristics. In this work, the production of XOS from lignocellulosic material was performed by combined chemical-enzymatic methods. Xylan was prepared from triploid Populas tomentosa, and bioconverted into XOS by crude xylanase solution obtained from Pichia stipitis. The effects of reaction time, temperature, enzyme dosage, and pH value on the production of XOS were fully evaluated. Under the optimal condition (25 U g−1 substrate, pH 5.4 and 50 °C), 36.8% of the xylan preparation was converted to XOS, equivalent to 3.95 mg/mL of the hydrolyzate. Xylobiose, xylotriose and xylotetrose were analyzed to be the main products of the enzymatic hydrolyzate, which together accounted for over 95% of the released oligosaccharides. Meanwhile, the effect of sonication pretreatment on the conversion efficiency of the xylan preparation was also investigated.  相似文献   
170.
Resistance of soybean cultivars, depending on single dominant genes to Phytophthora sojae, may easily be overcome by emerging new virulent races. Light microscopy (LM) and electron microscopy (EM) were used to study the infection process of the wild‐type isolate Ps411 and metalaxyl‐resistant mutant Ps411‐M of P. sojae in hypocotyls of soybean seedlings grown from untreated and metalaxyl‐treated seeds. The isolate Ps411‐M of P. sojae exhibited a high degree of resistance to metalaxyl compared to Ps411. The pathogenic fitness of Ps411‐M in hypocotyls of soybean seedlings was lower compared to Ps411. LM observations showed distinct differences in the infection process of both isolates in hypocotyls of treated soybean seedlings. EM studies revealed differences in the prepenetration stage between Ps411 and Ps411‐M on hypocotyls grown from seeds treated with 0.02% metalaxyl until the whole seed surface coated. The number of infection sites was markedly reduced and few hyphae continued to spread. Numerous ultrastructural alterations in hyphae were observed in treated hypocotyls infected with Ps411, including pronounced thickening of hyphal cell walls and encasement of haustorium‐like bodies; electron‐dense material was deposited in host cell walls in contact with hyphal cells. Neither the prepenetration process nor penetration or spread of hyphae in the hypocotyls of the resistant isolate was affected in treated compared to non‐treated tissue. While in treated hypocotyls infected with the wild‐type isolate, host defence reactions were induced, no such reactions were detected in treated hypocotyls infected with the resistant isolate. Hypocotyls from metalaxyl‐treated seeds infected with the wild‐type isolate resembled an incompatible interaction, whereas during infection with the metalaxyl‐resistant mutant, the compatible interaction was not changed.  相似文献   
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