The HECT family of E3 ubiquitin ligases and PTEN

Members of the HECT family of E3 ubiquitin ligases have emerged as prominent regulators of PTEN function, subcellular localization and levels. In turn this unfolding regulatory network is allowing for the identification of genes directly involved in both tumorigenesis at large and cancer susceptibility syndromes. While the complexity of this regulatory network is still being unraveled, these new findings are paving the way for novel therapeutic modalities for cancer prevention and therapy as well as for other diseases. Here we will review the signal transduction and therapeutic implications of the cross-talk between HECT family members and PTEN

The Equilibrium of Tumor Suppression: DUBs As Active Regulators of PTEN

PTEN is among the most commonly lost or mutated tumor suppressor genes in human cancer. PTEN, a bona fide lipid phosphatase that antagonizes the highly oncogenic PI3K-AKT-mTOR pathway, is considered a major dose-dependent tumor suppressor. Although PTEN function can be compromised by genetic mutations in inherited syndromes and cancers, posttranslational modifications of PTEN may also play key roles in the dynamic regulation of its function. Notably, deregulated ubiquitination and deubiquitination lead to detrimental impacts on PTEN levels and subcellular partitioning, promoting tumorigenesis. While PTEN can be targeted by HECT-type E3 ubiquitin ligases for nuclear import and proteasomal degradation, studies have shown that several deubiquitinating enzymes, including HAUSP/USP7, USP10, USP11, USP13, OTUD3 and Ataxin-3, can remove ubiquitin from ubiquitinated PTEN in cancer-specific contexts and thus reverse ubiquitination-mediated PTEN regulation. Researchers continue to reveal the precise molecular mechanisms by which cancer-specific deubiquitinases of PTEN regulate its roles in the pathobiology of cancer, and new methods of pharmacologically for modulating PTEN deubiquitinases are critical areas of investigation for cancer treatment and prevention. Here, we assess the mechanisms and functions of deubiquitination as a recently appreciated mode of PTEN regulation and review the link between deubiquitinases and PTEN reactivation and its implications for therapeutic strategies

Reconstruction of plasma density profiles by measuring spectra of radiation emitted from oscillating plasma dipoles

We suggest a new method for characterising non-uniform density distributions of plasma by measuring the spectra of radiation emitted from a localised plasma dipole oscillator excited by colliding electromagnetic pulses. The density distribution can be determined by scanning the collision point in space. Two-dimensional particle-in-cell simulations demonstrate the reconstruction of linear and nonlinear density profiles corresponding to laser-produced plasma. The method can be applied to a wide range of plasma, including fusion and low temperature plasmas. It overcomes many of the disadvantages of existing methods that only yield average densities along the path of probe pulses, such as interferometry and spectroscopy

Incidence and clinicopathologic behavior of uterine cervical carcinoma in renal transplant recipients

<p>Abstract</p> <p>Background</p> <p>Renal allograft recipients are reported to have a higher incidence of malignancy than the general population. This single hospital-based study examined the incidence and clinicopathologic behavior of uterine cervical carcinoma in renal transplant recipients.</p> <p>Methods</p> <p>Among 453 women receiving renal transplantation from January 1990 to December 2008, 5 patients were diagnosed with cervical carcinoma. Medical records of these 5 patients were retrospectively reviewed, and clinicopathologic data were collected and analyzed.</p> <p>Results</p> <p>The incidence of cervical carcinoma in renal transplant recipients was 58.1 out of 100,000 per year, which is 3.5 times higher than in the general Korean population. The mean interval between the time of renal transplantation and the time of cervical carcinoma diagnosis was 80.7 months. After a median follow-up of 96.2 months, there was no recurrence of the disease or death. In 4 patients who were positive from human papillomavirus in situ hybridization (HPV ISH), high or probably high risk HPV DNA was detected in all. Punctate staining of HPV ISH was detected in 3 out of 4 patients.</p> <p>Conclusions</p> <p>Higher incidence of cervical carcinoma is expected in renal transplant recipients, so appropriate surveillance is needed to ensure early detection and treatment of cervical carcinoma.</p

The involvement of AMPK/GSK3-beta signals in the control of metastasis and proliferation in hepato-carcinoma cells treated with anthocyanins extracted from Korea wild berry Meoru

BACKGROUND: Activation of the Wnt pathway is known to promote tumorigenesis and tumor metastasis, and targeting Wnt pathway inhibition has emerged as an attractive approach for controlling tumor invasion and metastasis. The major pathway for inhibiting Wnt is through the degradation of β-catenin by the GSK3-beta/CK1/Axin/APC complex. It was found that Hep3B hepato-carcinoma cells respond to anthocyanins through GSK3-beta-induced suppression of beta-catenin; however, they cannot dephosphorylate GSK3-beta without AMPK activation. METHODS: We tested the effects of anthocyanins on proliferation and apoptosis by MTT and Annexin V-PI staining in vitro. Mouse xenograft models of hepato-carcinomas were established by inoculation with Hep3B cells, and mice were injected with 50 mg/kg/ml of anthocyanins. In addition, protein levels of p-GSK3-beta, beta-catenin, p-AMPK, MMP-9, VEGF, and Ang-1 were also analyzed using western blot. RESULTS: Anthocyanins decrease phospho-GSK3-beta and beta-catenin expression in an in vivo tumor xenograft model, increase AMPK activity in this model, and inhibit cell migration and invasion, possibly by inhibiting MMP-2 (in vitro) and the panendothelial marker, CD31 (in vivo). To elucidate the role of the GSK3-beta/beta-catenin pathway in cancer control, we conditionally inactivated this pathway, using activated AMPK for inhibition. Further, we showed that AMPK siRNA treatment abrogated the ability of anthocyanins to control cell proliferation and metastatic potential, and Compound C, an AMPK inhibitor, could not restore GSK3-beta regulation, as exhibited by anthocyanins in Hep3B cells. CONCLUSION: These observations imply that the AMPK-mediated GSK3-beta/beta-catenin circuit plays crucial roles in inhibiting cancer cell proliferation and metastasis in anthocyanin-treated hepato-carcinoma cells of Meoru origin

Development of Kinematic Ephemeris Generator for Korea Pathfinder Lunar Orbiter (KPLO)

This paper presents a kinematic ephemeris generator for Korea Pathfinder Lunar Orbiter (KPLO) and its performance test results. The kinematic ephemeris generator consists of a ground ephemeris compressor and an onboard ephemeris calculator. The ground ephemeris compressor has to compress desired orbit propagation data by using an interpolation method in a ground system. The onboard ephemeris calculator can generate spacecraft ephemeris and the Sun/Moon ephemeris in onboard computer of the KPLO. Among many interpolation methods, polynomial interpolation with uniform node, Chebyshev interpolation, Hermite interpolation are tested for their performances. As a result of the test, it is shown that all the methods have some cases that meet requirements but there are some performance differences. It is also confirmed that, the Chebyshev interpolation shows better performance than other methods for spacecraft ephemeris generation, and the polynomial interpolation with uniform nodes yields good performance for the Sun/Moon ephemeris generation. Based on these results, a Kinematic ephemeris generator is developed for the KPLO mission. Then, the developed ephemeris generator can find an approximating function using interpolation method considering the size and accuracy of the data to be transmitted

Rubus Crataegifolius Bunge Regulates Adipogenesis Through Akt and Inhibits High-Fat Diet-Induced Obesity in Rats

BACKGROUND: Obesity is one of the greatest public health problems and major risk factors for serious metabolic diseases and significantly increases the risk of premature death. The aim of this study was to determine the inhibitory effects of Rubus crataegifolius Bunge (RCB) on adipocyte differentiation in 3 T3-L1 cells and its anti-obesity properties in high fat diet (HFD)-induced obese rats. METHODS: 3 T3-L1 adipocytes and HFD-induced obese rats were treated with RCB, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. RESULTS: RCB treatment significantly inhibited adipocyte differentiation by suppressing the expression of C/EBPβ, C/EBPα, and PPARγ in the 3 T3-L1 adipocytes. Subsequently, the expression of the PPARγ target genes aP2 and fatty acid synthase (FAS) decreased following RCB treatment during adipocyte differentiation. In uncovering the specific mechanism that mediates the effects of RCB, we demonstrated that the insulin-stimulated phosphorylation of Akt strongly decreased and that its downstream substrate phospho-GSK3β was downregulated following RCB treatment in the 3 T3-L1 adipocytes. Moreover, LY294002, an inhibitor of Akt phosphorylation, exerted stronger inhibitory effects on RCB-mediated suppression of adipocyte differentiation, leading to the inhibition of adipocyte differentiation through the downregulation of Akt signaling. An HFD-induced obesity rat model was used to determine the inhibitory effects of RCB on obesity. Body weight gain and fat accumulation in adipose tissue were significantly reduced by the supplementation of RCB. Moreover, RCB treatment caused a significant decrease in adipocyte size, associated with a decrease in epididymal fat weight. The serum total cholesterol (TC) and triglyceride (TG) levels decreased in response to RCB treatment, whereas HDL cholesterol (HDL-C) increased, indicating that RCB attenuated lipid accumulation in adipose tissue in HFD-induced obese rats. CONCLUSION: Our results demonstrate an inhibitory effect of RCB on adipogenesis through the reduction of the adipogenic factors PPARγ, C/EBPα, and phospho-Akt. RCB had a potent anti-obesity effect, reducing body weight gain in HFD-induced obese rats

Shock ion acceleration by an ultrashort circularly polarized laser pulse via relativistic transparency in an exploded target

We investigated ion acceleration by an electrostatic shock in an exploded target irradiated by an ultrashort, circularly polarized laser pulse by means of one- and three-dimensional particle-in-cell simulations. We discovered that the laser field penetrating via relativistic transparency (RT) rapidly heated the upstream electron plasma to enable the formation of a high-speed electrostatic shock. Owing to the RT-based rapid heating and the fast compression of the initial density spike by a circularly polarized pulse, a new regime of the shock ion acceleration driven by an ultrashort (20-40 fs), moderately intense (1-1.4 PW) laser pulse is envisaged. This regime enables more efficient shock ion acceleration under a limited total pulse energy than a linearly polarized pulse with crystal laser systems of lambda similar to 1 mu mopen

A laser-plasma accelerator driven by two-color relativistic femtosecond laser pulses

A typical laser-plasma accelerator (LPA) is driven by a single, ultrarelativistic laser pulse from terawatt- or petawatt-class lasers. Recently, there has been some theoretical work on the use of copropagating two-color laser pulses (CTLP) for LPA research. Here, we demonstrate the first LPA driven by CTLP where we observed substantial electron energy enhancements. Those results have been further confirmed in a practical application, where the electrons are used in a bremsstrahlung-based positron generation configuration, which led to a considerable boost in the positron energy as well. Numerical simulations suggest that the trailing second harmonic relativistic laser pulse is capable of sustaining the acceleration structure for much longer distances after the preceding fundamental pulse is depleted in the plasma. Therefore, our work confirms the merits of driving LPAs by two-color pulses and paves the way toward a downsizing of LPAs, making their potential applications in science and technology extremely attractive and affordable

Differential effect of NF-κB activity on β-catenin/Tcf pathway in various cancer cells

Abstractβ-Catenin/Tcf and NF-κB pathways play an important role in biological functions. We determined the underlying mechanisms of differential interaction between two pathways in various human cancer cell lines. NF-κB positively regulated β-catenin/Tcf pathways in human glioblastoma, whereas it has an opposite effect on β-catenin/Tcf pathways in colon, liver, and breast cancer cells. Expression of lucine zipper tumor suppressor 2 (lzts2) was positively regulated by NF-κB activity in colon, liver, and breast cancer cells, whereas negatively regulated in glioma cells. Downregulation of lzts2 increased the β-catenin/Tcf promoter activity and inhibited NF-κB-induced modulation of the nuclear translocation of β-catenin. These data indicate that the differential crosstalk between β-catenin/Tcf and NF-κB pathway in various cancer cells is resulted from the differences in the regulation of NF-κB-induced lzts2 expression