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Although water availability strongly controls gross primary production (GPP), the impact of soil moisture content (SMC) (wilting point) is poorly quantified on regional and global scales. In this study, we used 10 years of observations of solar‐induced chlorophyll fluorescence (SIF) from the Greenhouse gases Observing Satellite (GOSAT) satellite to estimate the wilting point of a semiarid grassland on the Mongolian Plateau. Radiative‐transfer model inversion and soil‐vegetation‐atmosphere transfer simulation were sequentially conducted to distinguish the drought impacts on plant physiology from the changes in the leaf‐canopy optical properties. We modified an existing inversion algorithm and the widely used Soil‐Canopy Observation of Photosynthesis and Energy fluxes model to adequately evaluate dryland features, for example, sparse canopy and strong convection. The modified model, with retrieved parameters and calibration to GOSAT SIF, predicted realistic GPP values. We found that (a) the SIF yield estimated from GOSAT showed a clear sigmoidal pattern in relation to drought, and the estimated wilting point matched ground‐based observations in the literature within ∼0.01 m3 m−3 for the SMC, (b) tuning the maximum carboxylation rate improved the SIF prediction after considering the changes in the leaf‐canopy optical properties, implying that GOSAT detected drought stress in leaf‐level photosynthesis, and (c) the surface energy balance significantly impacted the grassland's SIF; the modified model reproduced observed SIF well (mean bias = 0.004 mW m−2 nm−1 sr−1 in summer), whereas the original model predicted substantially low values under weak horizontal wind conditions. Some model‐observation mismatches in the SIF suggest that more research is needed for fluorescence parametrization (e.g., photoinhibition) and for additional observation constraints. Plain Language Summary: Solar‐induced chlorophyll fluorescence, a weak radiation emitted as a byproduct of photosynthesis, can potentially be used to assess plant physiological status, which is especially promising for evaluating poorly quantified soil drought (wilting) impacts on the carbon cycle. However, the potential of satellite‐observed fluorescence to improve wilting prediction by vegetation models has not been sufficiently explored because of the confounding effects of plant physiological stress and visible damage (i.e., leaf browning and defoliation). In this study, we distinguished physiological wilting from visible damage by estimating leaf pigment contents and leaf amounts from satellite‐observed reflectance with the aid of a radiative transfer model and a state‐of‐the‐art vegetation model. We found that some model modifications were necessary to adequately evaluate the dryland features, for example, sparse vegetation cover and thermally induced atmospheric flow. The observed fluorescence showed a clear nonlinear response to the soil moisture content, which is characteristic of wilting. The model‐based analysis suggested that the nonlinear response resulted from physiological stress, and the estimated wilting point matched the ground‐based observations in the literature well. Since our approach is based on biophysics and satellite data, our findings and methods should help in understanding and predicting terrestrial water and carbon cycles in other regions. Key Points: Satellite‐observed chlorophyll fluorescence showed a nonlinear wilting pattern in response to soil droughts on the Mongolian PlateauWe modified the Soil‐Canopy Observation of Photosynthesis and Energy fluxes (SCOPE) model and its ancillary radiative‐transfer inversion algorithm to adequately evaluate dryland featuresThe modifications enabled assessment of the physiological control of photosynthesis and retrieval of the wilting point of the study area [ABSTRACT FROM AUTHOR]

Background:Epithelial cells of endometriotic tissues are difficult to propagate in vitro as experimental material is scarce owing to their limited life span. However, there is an increasing concern regarding their malignant transformation in ovaries. The present study sought to generate their stable culture system.Methods and results:Purified epithelial cells isolated from ovarian endometriomas using microscopic manipulation were successfully immortalised by combinatorial transfection of human cyclinD1, cdk4 and human telomerase reverse transcriptase (hTERT) genes, whereas the introduction of hTERT alone, or together with cdk4, was insufficient for immortalisation, leading to cellular senescence. We confirmed stable cytokeratin expression in the immortalised cells, proving their epithelial origin. These cells expressed progesterone receptor B and showed significant growth inhibition by various progestins. Oestrogen receptor (ER) expression was detected in these cells, albeit at low levels. Additional overexpression of ERα generated stable cells with oestrogen-dependent growth activation. Soft-agar colony formation assay and nude mice xenograft experiments demonstrated that these cells, even those with additional inactivation of p53, did not have transformed phenotypes.Conclusion:We for the first time generated immortalised epithelial cells from ovarian endometrioma that retained sex steroid responsiveness. These cells are invaluable tools not only for the consistent in vitro work but also for the study of molecular pathogenesis or carcinogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

Background: Disabled phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase/extracellular signal-regulated kinase signalling is involved in endometrial carcinogenesis, and there is evidence that expression of epidermal growth factor receptor (EGFR) family members has a role in such intracellular signalling pathways. This study analysed the prognostic impact of EGFR family expression in endometrial cancer in relation to PI3K-AKT and MAPK-ERK signalling, as well as drug sensitivity.Methods and Results: Immunohistochemical analysis using 63 surgical specimens of endometrioid-type endometrial cancers revealed that EGFR, human epidermal growth factor receptor (HER)-2 and HER-4 were expressed in 25 (39.7%) of 63, 26 (41.3%) of 63 and 31 (49.2%) of 63 tumours, respectively. Gene amplification of HER-2 was observed in 2 of 26 patients with high HER-2 expression. Kaplan-Meier analysis revealed that high HER-2 expression was a factor that negatively influenced the progression-free and overall survival rate (P<0.05), and multivariate analysis showed high HER-2 expression to be an independent prognostic factor. Subsequently, we performed in vitro knockdown analysis to investigate the linkage between HER-2 expression and PI3K-AKT pathways. Short interfering RNA (siRNA)-based knockdown of HER-2 in endometrial cancer cells led to a significant reduction in phosphorylated AKT (p-AKT) expression, indicating the existence of a HER-2/PI3K-AKT axis. As the PI3K-AKT pathway is known to have crucial roles in anticancer drug sensitivity, we examined the involvement of HER-2 in sensitivity to paclitaxel. Short interfering RNA-based knockdown of HER-2 conferred increased sensitivity to paclitaxel in endometrial cancer cells, attenuating the induction of p-AKT on paclitaxel stimulation, which was cancelled by inactivating AKT by the introduction of a dominant-negative form.Conclusion: HER-2 is a significant prognostic factor of endometrioid-type endometrial cancer, as well as a key molecule that affects paclitaxel sensitivity by HER-2 interaction with the PI3K-AKT pathway. [ABSTRACT FROM AUTHOR]

In advanced industrial gas turbine systems, there has been a great demand for new single crystal (SC) superalloys with an excellent combination of high temperature creep strength, hot corrosion resistance and oxidation resistance. In the present study, twelve nickel based SC superalloys were designed with the aid of the d-electrons concept. Their chemical compositions were in the range 1·2–1·5%Ti, 3·8–6·5%Cr, 11%Co, 0–1·4%Mo, 0–3·0%Ru, 6·5–7·4%Ta, 5·0–6·4%W, 3·6–5·4%Re, 5·1–5·5%Al, 0·12–0·14%Hf and balanced Ni in wt-%. A series of experiments such as creep rupture tests, burner rig tests and cyclic oxidation tests were conducted with the heat treated SC specimens of these alloys. Almost all the designed alloys were found to be superior in creep rupture life to a second generation superalloy currently used in the world. In the hot corrosion resistance estimated from the burner rig tests, any designed alloys were similar or even superior to a second generation superalloy. The oxidation resistance was very different among the designed alloys, but some of them showed better resistance than the second generation superalloy. Thus the SC alloys containing about 4–5 wt-%Re had ∼30°C or more higher temperature capability than the second generation superalloy, while exhibiting excellent hot corrosion resistance and good oxidation resistance. [ABSTRACT FROM AUTHOR]

Epithelial ovarian carcinoma is thought to derive from ovarian surface epithelium (OSE). The black box of the early molecular changes in ovarian carcinogenesis is being interpreted by the development of experimental systems employing immortalised human OSE cells. However, the existing cell lines of the OSE cells have limited utility due to chromosomal instability. Our goal was to establish new immortalised human OSE cells that retain the original characteristics of the primary cells without chromosomal alterations. Using primary human OSE cells obtained from a postmenopausal patient with endometrial cancer, five cell lines ('HOSE1' lines) were newly established by infection with retroviral expression vectors containing type 16 human papillomavirus (HPV-16) E6, E7, a variant E6 (E6delta151), and Bmi1 polycomb gene, in combination with telomerase reverse transcriptase (hTERT). Consequently, five HOSE1s cell lines, HOSE1s-E6/hTERT, -E7/hTERT, -E6/E7/hTERT, -E6delta151/E7/hTERT, and -E6delta151/Bmi1/hTERT, grew beyond the population doubling number of 200. These cell lines, except for HOSE1-E6/hTERT, essentially showed the original features of the primary human OSE cells. Of them, HOSE1-E7/hTERT preserved diploidy in a kariotype analysis, and did not show transformed phenotypes in anchorage-independent growth and tumour formation. Thus, HOSE1-E7/hTERT may provide a novel model system with which to investigate the mechanisms of early molecular changes. [ABSTRACT FROM AUTHOR]

Here we show that human papillomavirus (HPV) E6 and E7 oncoproteins induce hWAPL expression. In addition, small interfering RNA (siRNA) of hWAPL suppressed the growth of tumours derived from SiHa cells in nude mice. Thus, hWAPL may be one of the effective targets of uterine cervical cancer therapy. [ABSTRACT FROM AUTHOR]

The present study was designed to examine the roles of p53, reactive oxygen species (ROS), and ceramide, and to determine their mutual relationships during tumor necrosis factor (TNF)-a-induced apoptosis of human glioma cells. In cells possessing wild-type p53, TNF-a stimulated ceramide formation via the activation of both neutral and acid sphingomyelinases (SMases), accompanied by superoxide anion (O2-•) production, and induced mitochondrial depolarization and cytochrome c release, whereas p53-deficient cells were partially resistant to TNF-a and lacked O2-• generation and neutral SMase activation. Restoration of functional p53 sensitized glioma cells expressing mutant p53 to TNF-a by accumulation of O2-•. z-IETD-fmk (benzyloxycarbonyl-Ile-Glu-Thr-Asp fluoromethyl ketone), but not z-DEVD-fmk (benzyloxycarbonyl-Asp-Glu-Val-Asp fluoromethyl ketone), blocked TNF-a-induced ceramide formation through both SMases as well as O2-• generation. Caspase-8 was processed by TNF-a regardless of p53 status of cells or the presence of antioxidants. Two separate signaling cascades, p53-mediated ROS-dependent and -independent pathways, both of which are initiated by caspase-8 activation, thus contribute to ceramide formation in TNF-a-induced apoptosis of human glioma cells.Cell Death and Differentiation (2004) 11, 997-1008. doi:10.1038/sj.cdd.4401438 Published online 7 May 2004 [ABSTRACT FROM AUTHOR]

Although the p53 tumor-suppressor gene product plays a critical role in apoptotic cell death induced by DNA-damaging chemotherapeutic agents, human glioma cells with functional p53 were more resistant to ?-radiation than those with mutant p53. U-87 MG cells with wild-type p53 were resistant to ?-radiation. U87-W E6 cells that lost functional p53, by the expression of type 16 human papillomavirus E6 oncoprotein, became susceptible to radiation-induced apoptosis. The formation of ceramide by acid sphingomyelinase (A-SMase), but not by neutral sphingomyelinase, was associated with p53-independent apoptosis. SR33557 (2-isopropyl-1-(4-[3-N-methyl-N-(3,4-dimethoxybphenethyl)amino]propyloxy)benzene-sulfonyl) indolizine, an inhibitor of A-SMase, suppressed radiation-induced apoptotic cell death. In contrast, radiation-induced A-SMase activation was blocked in glioma cells with endogenous functional p53. The expression of acid ceramidase was induced by ?-radiation, and was more evident in cells with functional p53. N-oleoylethanolamine, which is known to inhibit ceramidase activity, unexpectedly downregulated acid ceramidase and accelerated radiation-induced apoptosis in U87-W E6 cells. Moreover, cells with functional p53 could be sensitized to ?-radiation by N-oleoylethanolamine, which suppressed radiation-induced acid ceramidase expression and then enhanced ceramide formation. Sensitization to ?-radiation was also observed in U87-MG cells depleted of functional p53 by retroviral expression of small interfering RNA. These results indicate that ceramide may function as a mediator of p53-independent apoptosis in human glioma cells in response to ?-radiation, and suggest that p53-dependent expression of acid ceramidase and blockage of A-SMase activation play pivotal roles in protection from ?-radiation of cells with endogenous functional p53.Cell Death and Differentiation (2004) 11, 853-861. doi:10.1038/sj.cdd.4401428 Published online 16 April 2004 [ABSTRACT FROM AUTHOR]