Gö6983 attenuates breast cancer‐induced osteolysis by the apoptotic pathway

Bone metastasis caused by breast cancer leads to significant complications in treatment, and the resulting osteolysis considerably affects patients’ overall survival and quality of life. Gö6983 is a broad spectrum protein kinase C inhibitor. In this study, based on our finding that the Gö6983 inhibits osteolysis, we applied Gö6983 to the MDA‐MB‐231 breast cancer‐induced mouse bone metastasis model. And we found that Gö6983 has a strong inhibitory effect on the tumorigenic model of breast cancer by promoting the mitochondrial apoptosis pathway. Our study, therefore, demonstrates that Gö6983 has a potential inhibitory effect on breast cancer‐induced osteoclast activation and provides mechanistic insight that may prove useful for designing future treatments.     

A candidate PpRPH gene of the D locus controlling fruit acidity in peach

Plant Molecular Biology - A candidate gene, designate PpRPH, in the D locus was identified to control fruit acidity in peach. Fruit acidity has a strong impact on organoleptic quality of fruit....     

真菌反硝化过程及其驱动的N2O产生机制研究进展

真菌反硝化过程的发现打破了反硝化过程只发生在原核生物中的传统认识,是对全球微生物氮循环过程的重要补充。真菌参与的反硝化过程由于缺乏N_2O还原酶,其终产物为具有强辐射效应的温室气体N_2O。真菌在环境中分布广泛,生物量巨大,故真菌反硝化作用对全球N_2O释放通量的贡献是不容忽视的。近年来许多研究表明,真菌反硝化过程是自然环境中N_2O产生的重要途径。本文对反硝化真菌的发现、多样性及分布、产生N_2O的机制和活性测定方法等几个方面进行综述,并对未来的研究提出展望。     

Histone Acetyltransferase 1 Promotes Homologous Recombination in DNA Repair by Facilitating Histone Turnover

Faithful repair of DNA double-strand breaks is vital to the maintenance of genome integrity and proper cell functions. Histone modifications, such as reversible acetylation, phosphorylation, methylation, and ubiquitination, which collectively contribute to the establishment of distinct chromatin states, play important roles in the recruitment of repair factors to the sites of double-strand breaks. Here we report that histone acetyltransferase 1 (HAT1), a classical B type histone acetyltransferase responsible for acetylating the N-terminal tail of newly synthesized histone H4 in the cytoplasm, is a key regulator of DNA repair by homologous recombination in the nucleus. We found that HAT1 is required for the incorporation of H4K5/K12-acetylated H3.3 at sites of double-strand breaks through its HIRA-dependent histone turnover activity. Incorporated histones with specific chemical modifications facilitate subsequent recruitment of RAD51, a key repair factor in mammalian cells, to promote efficient homologous recombination. Significantly, depletion of HAT1 sensitized cells to DNA damage compromised the global chromatin structure, inhibited cell proliferation, and induced cell apoptosis. Our experiments uncovered a role for HAT1 in DNA repair in higher eukaryotic organisms and provide a mechanistic insight into the regulation of histone dynamics by HAT1.     

Penetration of verapamil across blood brain barrier following cerebral ischemia depending on both paracellular pathway and P-glycoprotein transportation

Background

Blood brain barrier (BBB) dysfunction is a common facet of cerebral ischemia, and the alteration of drug transporter, P-glycoprotein (P-gp), has been documented.

Aims

This study explores influence of damaged BBB and elevated P-gp on cerebral verapamil penetration after ischemia both in vivo and in vitro.

Methods

Middle cerebral artery occlusion (MCAO) induced ischemia/reperfusion (I/R) of rats, and Na₂S₂O₄ induced hypoxia/reoxygenation (H/R) damage of rat brain mirovessel endothelial cells (RBMECs) respectively, served as BBB breakdown model in vivo and in vitro. Evans-Blue (EB) extravagation and ¹²⁵I-albumin were used to quantify BBB dysfunction; UPLC–MS/MS analytical method was performed to determine accurately the concentration of verapamil in brain tissue and cell. Flow cytometry, immunohistochemistry and western blotting were applied to evaluate transport function and protein expression of P-gp.

Results

Overexpressed ICAM-1 and MMP-9 mediated BBB dysfunction after ischemia, which induced EB leakage and ¹²⁵I-albumin uptake increase. Enhanced accumulation of verapamil in brain tissue, but intracellular concentration reduced evidently after H/R injury. Transcellular transportation of verapamil elevated when P-gp function or expression was inhibited after H/R injury.

Conclusion

These data indicated that BBB penetration of verapamil under ischemia condition was not only depending on BBB breakdown, but also regulated by P-gp.     

不同CO2浓度变化下干旱对冬小麦叶面积指数的影响差异

叶面积指数是作物生长状况的一个重要表征参数,也是研究陆地生态系统的一个重要的参数.当今世界温室气体排放逐年上升,气候变暖趋势明显,对气候变化敏感的农业将受到影响.在全球变化的背景下,采用农业技术转移决策支持系统(DSSAT)系统,通过在黄淮海平原典型站点模拟3种CO2浓度条件下冬小麦在水分充足和水分亏缺2种情境下的生长过程,分析不同CO2浓度下水分亏缺对冬小麦叶面积指数的影响差异.研究发现,CO2浓度升高对叶面积指数增长有促进作用,且在干旱情况下对叶面积指数的正效应比湿润情况下更为明显,在CO2浓度倍增条件下,发生水分亏缺的作物叶面积指数数倍增长.研究结论有助于分析CO2浓度变化对农作物生长过程的影响,为农田水分管理提供依据,又为估算叶面积指数提出了一种模型的方法.     

Temporal and spatial variations of chemical oxygen demand in Lake Taihu,China, from 2005 to 2009

We undertook a study in Lake Taihu, China, from 2005 to 2009 including a total of 639 samples to determine: (i) the seasonal dynamics and spatial distribution of the chemical oxygen demand (COD) and (ii) the relationships between the COD concentration and the biochemical oxygen demand (BOD), phytoplankton pigment, total dissolved nitrogen (TDN), and total dissolved phosphorus (TDP) concentrations, as well as the chromophoric dissolved organic matter (CDOM) absorption coefficient. There were significant spatial differences in the COD concentration, which gradually decreased from Zhushan Bay in the northwest, to the north, the lake center, and the southeast of the lake. The COD concentration was significantly higher at near-shore sites than that at open water sites. The mean COD concentrations were significantly higher in the spring and summer than in the winter and autumn. The lowest annual mean COD concentration appeared in 2009, which could be attributed to improvements in water quality management and high rainfall. The COD concentrations in all four seasons were strongly correlated with phytoplankton pigment, suggesting that extracellular release of COD from phytoplankton was an important COD source. The correlation coefficients between the COD and phytoplankton pigment concentrations were higher in the spring, summer, and autumn than in the winter, showing a more important contribution of phytoplankton degradation to COD in the algal bloom season than in the non-algal bloom season. These new data on the temporal and spatial characteristics of the COD in Lake Taihu will be crucial for developing future strategies for water quality management.     

Astragaloside IV suppresses transforming growth factor-β1-induced epithelial–mesenchymal transition through inhibition of Wnt/β-catenin pathway in glioma U251 cells

ABSTRACT

Astragaloside IV (AS#IV) has previously demonstrated antitumoractivity. We investigated the effect and mechanisms of AS#IV in relation to epithelial–mesenchymal transition (EMT), viainterference with the Wnt/β-catenin signaling pathway in gliomaU251 cells. Induction of glioma U251 cells by transforming growthfactor (TGF)#β1 activated EMT, including switching E#cadherin toN-cadherin and altering the expression of Wnt/β-catenin signalingpathway components such as vimentin, β-catenin, and cyclin-D1.AS-IV inhibited the viability, invasion, and migration of TGF-β1-induced glioma U251 cells. AS-IV also interfered with the TGF#β1-induced Wnt/β-catenin signaling pathway in glioma U251 cells.These findings indicate that AS#IV prohibits TGF#β1-induced EMTby disrupting the Wnt/β-catenin pathway in glioma U251 cells. AS#IV may thus be a potential candidate agent for treating glioma andother central nervous system tumors.