Regulation of ATR-CHK1 signaling by ubiquitination of CLASPIN.

DNA replication forks are frequently forced into stalling by persistent DNA aberrations generated from endogenous or exogenous insults. Stalled replication forks are catastrophic for genome integrity and cell survival if not immediately stabilized. The ataxia-telangiectasia and RAD3-related kinase (ATR)-CLASPIN-checkpoint kinase 1 (CHK1) signaling cascade is a pivotal mechanism that initiates cell-cycle checkpoints and stabilizes stalled replication forks, assuring the faithful duplication of genomic information before entry into mitosis. The timely recovery of checkpoints after stressors are resolved is also crucial for normal cell proliferation. The precise activation and inactivation of ATR-CHK1 signaling are usually efficiently regulated by turnover and the cellular re-localization of the adaptor protein CLASPIN. The ubiquitination-proteasome-mediated degradation of CLASPIN, driven by APC/CCDH1 and SCFßTrCP, results in a cell-cycle-dependent fluctuation pattern of CLASPIN levels, with peak levels seen in S/G2 phase when it functions in the DNA replisome or as an adaptor protein in ATR-CHK1 signaling under replication stress. Deubiquitination mediated by a series of ubiquitin-specific protease family proteins releases CLASPIN from proteasome-dependent destruction and activates the ATR-CHK1 checkpoint to overcome replication stress. Moreover, the non-proteolytic ubiquitination of CLASPIN also affects CHK1 activation by regulating CLASPIN localization. In this review, we discuss the functions of CLASPIN ubiquitination with specific linkage types in the regulation of the ATR-CHK1 signaling pathway. Research in this area is progressing at pace and provides promising chemotherapeutic targets.

[Monitoring "green tide" in the Yellow Sea and the East China Sea using multi-temporal and multi-source remote sensing images].

Landsat-TM (Theme Mapper) and EOS (Earth Observing System)-MODIS (MODerate resolution Imaging Spectrora-diometer) Terra/Aqua images were used to monitor the macro-algae (Ulva prolifera) bloom since 2007 at the Yellow Sea and the East China Sea. At the turbid waters of Northern Jiangsu Shoal, there is strong spectral mixing behavior, and satellite images with finer spatical resolution are more effective in detection of macro-algae patches. Macro-algae patches were detected by the Landsat images for the first time at the Sheyang estuary where is dominated by very turbid waters. The MODIS images showed that the macro-algae from the turbid waters near the Northern Jiangsu Shoal drifted southwardly in the early of May and affected the East China Sea waters; with the strengthening east-asian Summer Monsoon, macro-algae patches mainly drifted in a northward path which was mostly observed at the Yellow Sea. Macro-algae patches were also found to drift eastwardly towards the Korea Peninsular, which are supposed to be driven by the sea surface wind.

The vascular endothelial growth factor expression and vascular regeneration in infarcted myocardium by skeletal muscle satellite cells.

BACKGROUND: Myocardial infarction results in tissue necrosis, leading to cell loss and ultimately to cardiac failure. Implantation of skeletal muscle satellite cells into the scar area may compensate for the cell loss and provides a new strategy for infarct therapy. Vascular endothelial growth factor (VEGF) is a promising reagent for inducing myocardial angiogenesis. Skeletal myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that VEGF expression and vascular regeneration increased in infarcted myocardium by skeletal muscle satellite cells, which can promote vascular producing and improve survival environment in infarcted myocardium. METHODS: The skeletal muscle satellite cells were implanted into the infarcted myocardium in a model through ligated left anterior artery in Louis Inbrad Strain rat. Specimens were got for identifying the expression of VEGF and the density of vascular by immunochemical method at two weeks after implantation. RESULTS: The proliferation and differentiation of the skeletal muscle satellite cell was very well. The expression of VEGF was higher in the implanted group (146.83 +/- 2.49) than that in the control group (134.26 +/- 6.84) (P < 0.05). The vascular density in the implanted group (13.00 +/- 1.51) was also higher than that in the control (10.68 +/- 1.79) (P < 0.05). CONCLUSION: The implanted satellite cell could excrete growth factor that would induce angiogenesis and improve cell survival environment in infarcted myocardium.

Vestibular destruction by slow infusion of gentamicin into semicircular canals.

Intratympanic or round window application of gentamicin is often used to alleviate disabling vertigo arising from unilateral Meniere's disease; however, treatment is often accompanied by hearing loss because the drug initially enters the cochlea before diffusing to the vestibular system. In order to enhance vestibular damage and reduce the risk of hearing loss, gentamicin was infused directly into the vestibular system. An osmotic pump containing 50, 100, 200 or 400 microg/ml of gentamicin was infused into the superior semicircular canal of the chinchilla for 7 days. Afterwards, vestibular damage was evaluated by measuring the decline in hair cell density in the utricle, saccule and superior semicircular canals. Auditory damage was assessed with distortion product otoacoustic emissions (DPOAE) and outer hair cell (OHC) and inner hair cell (IHC) loss. Infusion with the two lowest gentamicin concentrations resulted in significant hair cell loss and reduced duration of the nystagmus response, but had little or no effect on OHC or DPOAE. Higher doses of gentamicin damaged cochlear hair cells and reduced the DPOAE. In conclusion, slow infusion of a low dose of gentamicin into the semicircular canals mainly damages the vestibular hair cells and inactivates the nystagmus response without damaging cochlear hair cells or DPOAE.