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851.
Ren-Jun Hsu Jar-Yi Ho Tai-Lung Cha Dah-Shyong Yu Chieh-Lin Wu Wei-Ping Huang Pauling Chu Ying-Hsin Chen Jiann-Torng Chen Cheng-Ping Yu 《PloS one》2012,7(10)
Renal cell carcinoma (RCC) is a malignancy with poor prognosis. WNT/β-catenin signaling dysregulation, especially β-catenin overactivation and WNT antagonist silencing, is associated with RCC carcinogenesis and progression. However, the role of WNT ligands in RCC has not yet been determined. We screened 19 WNT ligands from normal kidney and RCC cell lines and tissues and found that WNT10A was significantly increased in RCC cell lines and tissues as compared to that in normal controls. The clinical significance of increase in WNT10A was evaluated by performing an immunohistochemical association study in a 19-year follow-up cohort comprising 284 RCC and 267 benign renal disease (BRD) patients. The results of this study showed that WNT10A was dramatically upregulated in RCC tissues as compared to that in BRD tissues. This result suggests that WNT10A, nuclear β-catenin, and nuclear cyclin D1 act as independent risk factors for RCC carcinogenesis and progression, with accumulative risk effects. Molecular validation of cell line models with gain- or loss-of-function designs showed that forced WNT10A expression induced RCC cell proliferation and aggressiveness, including higher chemoresistance, cell migration, invasiveness, and cell transformation, due to the activation of β-catenin-dependent signaling. Conversely, WNT10A siRNA knockdown decreased cell proliferation and aggressiveness of RCC cells. In conclusion, we showed that WNT10A acts as an autocrine oncogene both in RCC carcinogenesis and progression by activating WNT/β-catenin signaling. 相似文献
852.
853.
DM Iglesias R El-Kares A Taranta F Bellomo F Emma M Besouw E Levtchenko J Toelen L van den Heuvel L Chu J Zhao YK Young N Eliopoulos P Goodyer 《PloS one》2012,7(8):e42840
Cystinosis is a rare disease caused by homozygous mutations of the CTNS gene, encoding a cystine efflux channel in the lysosomal membrane. In Ctns knockout mice, the pathologic intralysosomal accumulation of cystine that drives progressive organ damage can be reversed by infusion of wildtype bone marrow-derived stem cells, but the mechanism involved is unclear since the exogeneous stem cells are rarely integrated into renal tubules. Here we show that human mesenchymal stem cells, from amniotic fluid or bone marrow, reduce pathologic cystine accumulation in co-cultured CTNS mutant fibroblasts or proximal tubular cells from cystinosis patients. This paracrine effect is associated with release into the culture medium of stem cell microvesicles (100-400 nm diameter) containing wildtype cystinosin protein and CTNS mRNA. Isolated stem cell microvesicles reduce target cell cystine accumulation in a dose-dependent, Annexin V-sensitive manner. Microvesicles from stem cells expressing CTNS(Red) transfer tagged CTNS protein to the lysosome/endosome compartment of cystinotic fibroblasts. Our observations suggest that exogenous stem cells may reprogram the biology of mutant tissues by direct microvesicle transfer of membrane-associated wildtype molecules. 相似文献
854.
Phosphatidylinositol monophosphate 5-kinase (PIP5K) catalyzes the synthesis of PI-4,5-bisphosphate (PtdIns(4,5)P(2)) by phosphorylation of PI-4-phosphate at the 5 position of the inositol ring, and is involved in regulating multiple developmental processes and stress responses. We here report on the functional characterization of Arabidopsis PIP5K2, which is expressed during lateral root initiation and elongation, and whose expression is enhanced by exogenous auxin. The knockout mutant pip5k2 shows reduced lateral root formation, which could be recovered with exogenous auxin, and interestingly, delayed root gravity response that could not be recovered with exogenous auxin. Crossing with the DR5-GUS marker line and measurement of free IAA content confirmed the reduced auxin accumulation in pip5k2. In addition, analysis using the membrane-selective dye FM4-64 revealed the decelerated vesicle trafficking caused by PtdIns(4,5)P(2) reduction, which hence results in suppressed cycling of PIN proteins (PIN2 and 3), and delayed redistribution of PIN2 and auxin under gravistimulation in pip5k2 roots. On the contrary, PtdIns(4,5)P(2) significantly enhanced the vesicle trafficking and cycling of PIN proteins. These results demonstrate that PIP5K2 is involved in regulating lateral root formation and root gravity response, and reveal a critical role of PIP5K2/PtdIns(4,5)P(2) in root development through regulation of PIN proteins, providing direct evidence of crosstalk between the phosphatidylinositol signaling pathway and auxin response, and new insights into the control of polar auxin transport. 相似文献
855.
With density function theory BLYP/DNP method, together with homodesmotic reactions and isodesmic reactions, we calculated
the resonance energies of some explosives, including eight nitro compounds which contains benzene rings, three nitro compounds
which contains azaheterocycles (2,4-dinitroimidazole (2,4-DNI), 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) and 2,4,6-trinitro-1,3,5-triazine)
and one nitrogen-rich energetic compound of 3,3’-azobis(6-amino-s-tetrazine) (DAAT). The results indicate that their resonance
energies are in relation to their shock sensitivity which measuring their threshold pressures of initiation, that is, the
lower the resonance energy is, the higher the shock sensitivity of the explosive behaves. And this measuring method according
to resonance energy is based on the global property of the molecule instead of the local one, such as one nitro group in the
molecule. It is meaningful to calculate resonance energies of these kind of compounds quickly and accurately because resonance
structures exist widely in these organic compounds and resonance energies may play a significant role in determining their
shock sensitivity, and it is helpful in the rational design or synthesis of high energy and insensitive materials. 相似文献
856.
Larvae of the black soldier fly, Hermetia illucens are well‐known fly larvae that inhabit many countries around the world. Antimicrobial agents derived from the larvae may be among the substances that are produced in the body for their survival. This study was carried out to identify the antimicrobial effects of H. illucens larvae that commonly inhabit animal waste and food waste. To evaluate the pharmacological effects of H. illucens larvae extracts, the larvae were extracted by various organic solvents, and their antibacterial effects were determined by antimicrobial methods, such as agar disk diffusion and turbidometric assays. The methanol extracts (ME) indicated antibacterial effects against the proliferation of Klebsiella pneumoniae, Neisseria gonorrhoeae and Shigella sonnei. However, antibacterial effects were not induced in Gram‐positive bacteria such as Bacillus subtilis, Streptococcus mutans and Sarcina lutea. The bacterial growth treated with ME was strongly inhibited from 20 mg/mL in a dose‐dependent manner compared with other extracts, and antibacterial activity gradually decreased after 24 h. Moreover, the minimal inhibitory concentration (MIC) values of ME against Klebsiella pneumoniae, Neisseria gonorrhoeae and Shigella sonnei for 12 h were measured as 44.74 mg/mL, 43.98 mg/mL and 43.96 mg/mL, respectively. These results demonstrate that ME of H. illucens larvae not only has antibacterial activity which strongly inhibits the growth and proliferation of the bacteria but also unique properties which effectively block the viability of the bacteria. 相似文献
857.
858.
Yen-Ching Chen Ping-Keung Yip Yi-Ling Huang Yu Sun Li-Li Wen Yi-Min Chu Ta-Fu Chen 《PloS one》2012,7(12)
Background
Toll like receptor 4 (TLR4) has been related to inflammation and beta-amyloid deposition in Alzheimer''s disease (AD) brain. No study has explored the association between haplotype-tagging single nucleotide polymorphisms (htSNPs) of TLR4 and AD risk previously and ApoE e4 status alone showed low sensitivity in identifying late-onset AD (LOAD) patients.Methods
A total of 269 LOAD patients were recruited from three hospitals in northern Taiwan (2007–2010). Controls (n = 449) were recruited from elderly health checkup and volunteers of the hospital during the same period of time. Five common (frequency≥5%) TLR4 htSNPs were selected to assess the association between TLR4 polymorphisms and the risk of LOAD in the Chinese ethnic population.Results
Homozygosity of TLR4 rs1927907 was significantly associated with an increased risk of LOAD [TT vs. CC: adjusted odds ratio (AOR) = 2.45, 95% confidence interval (CI) = 1.30–4.64]. After stratification, the association increased further in ApoE e4 non-carriers (AOR = 3.07) and in hypertensive patients (AOR = 3.60). Haplotype GACGG was associated with a decreased risk of LOAD (1 vs. 0 copies: AOR = 0.59, 95% CI = 0.36–0.96; 2 vs. 0 copies: AOR = 0.31, 95% CI = 0.14–0.67) in ApoE e4 non-carriers. ApoE e4 status significantly modified this association (p interaction = 0.01). These associations remained significant after correction for multiple tests.Conclusions
Sequence variants of TLR4 were associated with an increased risk of LOAD, especially in ApoE e4 non-carriers and in hypertensive patients. The combination of TLR4 rs1927907 and ApoE e4 significantly increased the screening sensitivity in identifying LOAD patients from 0.4 to 0.7. 相似文献859.
Difficulty in species identification of Sargassum (Sargassaceae, Fucales) is partly attributed to the high polymorphism among its individuals and populations. This study aimed at assessing morphological and genetic variations in two varieties, var. hemiphyllum J. Agardh and var. chinense J. Agardh, of Sargassum hemiphyllum (Turner) C. Agardh, a widely distributed species in the northwestern Pacific. We investigated 26 measurable, five numerical, and 33 categorical morphological parameters associated with different branching levels of specimens from each of six localities within its distribution range using cluster analysis (CA) and principal coordinate analysis (PCoA). Leaf size of the primary and secondary branching levels and the vesicle size of the secondary branches of the specimens examined were determined to be the most important morphological parameters that were significantly different among populations. Change in leaf and vesicle length of individuals among the six populations followed a latitudinal gradient, with smaller leaves and vesicles associated with northern populations and larger ones in the southern populations. The possible influence of the gradual change in sea surface temperatures (SSTs) along this gradient in the northwestern Pacific on leaf and vesicle morphologies of this species was suggested. PCR‐RFLP analysis of the RUBISCO spacer in the chloroplast genome revealed two distinct and highly homogenous clades, a China clade and a Japan‐Korea clade, which corresponded to var. chinense and var. hemiphyllum, respectively. The formation of refugia along the “Paleo‐coast” in the East China Sea during glacial periods is suggested to have led to the vicariance of ancestral populations of S. hemiphyllum and thus to have promoted genetic differentiation. The massive freshwater outflow of the Yellow and Yangtze rivers may continue to act as a barrier, prolonging the allopatric distribution of the two varieties. 相似文献
860.
Chu D 《Journal of theoretical biology》2008,253(2):355-362
A group-selection model for the evolutionary origin of phase-variation in E. coli is proposed. Populations of commensal strains of E. coli populating mammalian hosts modulate its immune defenses through population-level control of the expression of fimbriae. At any time only a proportion of the population expresses these cell-surface adhesins. Collectively they elicit a host-based nutrient release if the fimbriae expression is low. Too high levels of fimbriation would provoke an inflammatory response and thus intolerable conditions for the cells. The optimal level of fimbriation is a group property and its evolution is difficult to explain by naive individual selection scenarios. This article presents a computational model to simulate the evolution of fimbriae. The two main conclusions of this contribution are: (i) the evolution of this group property requires the population to be partitioned into weakly interacting sub-populations. (ii) Given certain scenarios evolution consistently under-performs, in the sense that it does not find the optimal level of fimbriation. 相似文献