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781.
Pasupathi Sundaramoorthy Jae Jun Sim Yeong-Su Jang Siddhartha Kumar Mishra Keun-Yeong Jeong Poonam Mander Oh Byung Chul Won-Sik Shim Seung Hyun Oh Ky-Youb Nam Hwan Mook Kim 《PloS one》2015,10(1)
Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+) levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain) in a dose-dependent manner. Phosphorylated FAK (p-FAK) was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer. 相似文献
782.
Youngwoo Bryan Yoon Je-Yeon Yun Wi Hoon Jung Kang Ik K. Cho Sung Nyun Kim Tae Young Lee Hye Yoon Park Jun Soo Kwon 《PloS one》2015,10(8)
Background
The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered.Methods
To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl’s gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls.Results
Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl’s gyrus seeds. From the left planum temporale seed, the FEP and UHR groups exhibited increased connectivity to the bilateral dorsolateral prefrontal cortex. In contrast, the FEP and UHR groups demonstrated decreased connectivity from the bilateral Heschl’s gyrus seeds to the dorsal anterior cingulate cortex. The enhanced connectivity between the left planum temporale and right dorsolateral prefrontal cortex was positively correlated with positive symptom severity in individuals at UHR (r = .34, p = .03).Conclusions
These findings corroborate the fronto-temporal connectivity disruption hypothesis in schizophrenia by providing evidence supporting the altered fronto-temporal intrinsic functional connection at earlier stages of psychosis. Our data indicate that subregion-specific aberrant fronto-temporal interactions exist in the STG at the early stage of psychosis, thus suggesting that these aberrancies are the neural underpinning of proneness to psychosis. 相似文献783.
784.
巢蛋白(nestin)属Ⅵ类中等纤维蛋白。最初在神经系统发育早期发现有该蛋白的表达。后在正常神经系统中发现仅在未分化的神经前体细胞中有nestin的短暂表达,分化后在神经元和神经胶质细胞中分别被NF(neurofilament,神经丝)和GFAP(Glial fibrillary acidic protein,神经胶质元纤维酸性蛋白)所代替。所以nestin的表达通常被视为神经前体细胞的标志之一。就我们所知,目前商品化nestin的抗体都是鼠抗鼠(克隆Rat401)的抗体,而人鼠之间该蛋白序列的同源性仅为50%左 相似文献
785.
786.
Mesorhizobium huakuii is a free-living bacterium which is capable of establishing a specific symbiotic relationship with Astragalus sinicus, an important winter green manure widely used in Eastern Asia, allowing for nitrogen fixing during this process. Previous studies demonstrate that M.␣huakuii produces quorum-sensing molecules at high cell density and quorum sensing plays a role in biofilm formations. In this study, we isolated and characterized two quorum-sensing deficient mutants in M. huakuii. Analysis of the flanking region of transposon insertions indicated that autoinducer synthase related genes are not homologous to acyl homoserine lactone (AHL) synthase genes that are shared among many Gram-negative bacteria, but related to peptide synthesis, indicating that M. huakuii quorum-sensing signals are distinct from AHLs. Compared with the wild-type strains, these quorum-sensing deficient mutants promoted their growth rate and were defective in nodule formation on host plants, indicative of a critical role of quorum sensing in M.␣huakuii during the host–bacterium symbiotic interaction.Yijing Gao and Zengtao Zhong contributed equally to this work. 相似文献
787.
Chemical synthesis of complex-type glycans 1 and 2 derived from eggs of parasitic helminths, Schistosoma mansoni and Schistosoma japonicum, is described. These branched sugar chains were synthesized regio- and stereoselectively by using beta-mannosylation, desilylation under high pressure, and glycosylation in frozen solvent as key transformations. 相似文献
788.
789.
ICP34.5, encoded by herpes simplex virus 1, is a protein phosphatase 1 (PP1) regulatory subunit that mediates dephosphorylation of the alpha subunit of translation initiation factor 2 (eIF2alpha). However, the mechanism of its action remains poorly understood. Here, we show that amino acid substitutions in the arginine-rich motif have differential effects on ICP34.5 activity. The phenotypes parallel with viral protein synthesis and cytopathic effects in virus infected cells. Besides the consensus PP1 binding motif, the Arg-motif appears to enhance the interaction between ICP34.5 and PP1. These results suggest that concerted action between the PP1 binding domain and the effector domain of ICP34.5 is crucial for eIF2alpha dephosphorylation and viral protein synthesis. 相似文献
790.
Liu J Reedy MC Goldman YE Franzini-Armstrong C Sasaki H Tregear RT Lucaveche C Winkler H Baumann BA Squire JM Irving TC Reedy MK Taylor KA 《Journal of structural biology》2004,147(3):268-282
As a first step toward freeze-trapping and 3-D modeling of the very rapid load-induced structural responses of active myosin heads, we explored the conformational range of longer lasting force-dependent changes in rigor crossbridges of insect flight muscle (IFM). Rigor IFM fibers were slam-frozen after ramp stretch (1000 ms) of 1-2% and freeze-substituted. Tomograms were calculated from tilt series of 30 nm longitudinal sections of Araldite-embedded fibers. Modified procedures of alignment and correspondence analysis grouped self-similar crossbridge forms into 16 class averages with 4.5 nm resolution, revealing actin protomers and myosin S2 segments of some crossbridges for the first time in muscle thin sections. Acto-S1 atomic models manually fitted to crossbridge density required a range of lever arm adjustments to match variably distorted rigor crossbridges. Some lever arms were unchanged compared with low tension rigor, while others were bent and displaced M-ward by up to 4.5 nm. The average displacement was 1.6 +/- 1.0 nm. "Map back" images that replaced each unaveraged 39 nm crossbridge motif by its class average showed an ordered mix of distorted and unaltered crossbridges distributed along the 116 nm repeat that reflects differences in rigor myosin head loading even before stretch. 相似文献