WRKY proteins are transcription factors (TFs) that regulate the expression of defense-related genes. The salicylic acid (SA)-inducible Oryza sativa WRKY6 (OsWRKY6) was identified as a positive ...regulator of Oryza sativa pathogenesis-related 10a (OsPR10a) by transient expression assays. A physical interaction between OsWRKY6 and W-box-like element 1 (WLE1), which positively regulates OsPR10a/probenazole induced protein 1 expression, was verified in vitro.
Several pathogenesis-related (PR) genes were constitutively activated, including OsPR10a, and transgenic rice (Oryza sativa) plants overexpressing (ox) OsWRKY6 exhibited enhanced disease resistance to pathogens. By contrast, PR gene induction was compromised in transgenic OsWRKY6-RNAi lines, suggesting that OsWRKY6 is a positive regulator of defense responses. OsWRKY6-ox lines displayed leaf lesions, and increased OsWRKY6 levels caused cell death.
Salicylic acid (SA) concentrations were higher in OsWRKY6-ox lines than in wild-type (WT) plants, and transcript levels of Oryza sativa isochorismate synthase 1 (OsICS1), which encodes a major enzyme involved in SA biosynthesis, were higher in OsWRKY6-ox lines than in WT. OsWRKY6 directly bound to the OsICS1 promoter in vivo. This indicates that OsWRKY6 can directly regulate OsICS1 expression and thereby increase SA concentrations. OsWRKY6 autoregulates its own expression. OsWRKY6 protein degradation is possibly regulated by ubiquitination.
Our results suggest that OsWRKY6 positively regulates defense responses through activation of OsICS1 expression and OsWRKY6 stabilization.
Iron–chromium–aluminum alloys containing 15–20wt.% Cr and 4–6wt.% Al have shown excellent corrosion resistance in the temperature range up to 600°C or higher in liquid lead and lead–bismuth eutectic ...environments by the formation of protective Al2O3 layers. However, the higher Cr and Al concentrations in ferritic alloys could be problematic because of severe embrittlement in the manufacturing process as well as in service, caused by the formation of brittle phases. For this reason, efforts worldwide have so far mainly focused on the development of aluminizing surface treatments. However, aluminizing surface treatments have major disadvantages of cost, processing difficulties and reliability issues. In this study, a new FeCrAl alloy is proposed for structural materials in lead and lead–bismuth cooled nuclear applications. The alloy design relied on corrosion experiments in high temperature lead and lead–bismuth eutectic environments and computational thermodynamic calculations using the commercial software, JMatPro. The design of new alloys has focused on the optimization of Cr and Al levels for the formation of an external Al2O3 layer which can provide excellent oxidation and corrosion resistance in liquid lead alloys in the temperature range 300–600°C while still retaining workable mechanical properties.
Key message
OsWRKY51 functions as a positive transcriptional regulator in defense signaling against
Xanthomonas oryzae pv. oryzae
by direct DNA binding to the promoter of defense related gene, ...OsPR10a
.
OsWRKY51 in rice (
Oryza sativa
L.) is induced by exogenous salicylic acid (SA) and inoculation with
Xanthomonas oryzae pv. oryzae
(
Xoo
). To examine the role of OsWRKY51 in the defense response of rice, we generated
OsWRKY51
overexpressing and underexpressing transgenic rice plants.
OsWRKY51
-overexpressing transgenic rice lines were more resistant to
Xoo
and showed greater expression of defense-related genes than wild-type (WT) plants, while
OsWRKY51
-underexpressing lines were more susceptible to
Xoo
and showed less expression of defense-associated genes than WT plants. Transgenic lines overexpressing OsWRKY51 showed growth retardation compared to WT plants. In contrast, transgenic lines underexpressing OsWRKY51 by RNA interference showed similar plant height with WT plants. Transient expression of OsWRKY51-green fluorescent protein fusion protein in rice protoplasts revealed that OsWRKY51 was localized in the nucleus. OsWRKY51 bound to the W-box and WLE1 elements of the
OsPR10a
promoter. Based on these results, we suggest that OsWRKY51 is a positive transcriptional regulator of defense signaling and has direct DNA binding ability to the promoter of
OsPR10a
, although it is reported to be a negative regulator in GA signaling.
SUMMARY
Many ubiquitin E3 ligases function in plant immunity. Here, we show that Oryza sativa (rice) DDB1 binding WD (OsDWD1) suppresses immune responses by targeting O. sativa non‐expresser of ...pathogenesis‐related gene 1 (OsNPR1) for degradation. Knock‐down and overexpression experiments in rice plants showed that OsDWD1 is a negative regulator of the immune response and that OsNPR1 is a substrate of OsDWD1 and a substrate receptor of OsCRL4. After constructing the loss‐of‐function mutant OsDWD1R239A, we showed that the downregulation of OsNPR1 seen in rice lines overexpressing wild‐type (WT) OsDWD1 (OsDWD1WT‐ox) was compromised in OsDWD1R239A‐ox lines, and that OsNPR1 upregulation enhanced resistance to pathogen infection, confirming that OsCRL4OsDWD1 regulates OsNPR1 protein levels. The enhanced disease resistance seen in OsDWD1 knock‐down (OsDWD1‐kd) lines contrasted with the reduced disease resistance in double knock‐down (OsDWD1/OsNPR1‐kd) lines, indicating that the enhanced disease resistance of OsDWD1‐kd resulted from the accumulation of OsNPR1. Moreover, an in vivo heterologous protein degradation assay in Arabidopsis thaliana ddb1 mutants confirmed that the CUL4‐based E3 ligase system can also influence OsNPR1 protein levels in Arabidopsis. Although OsNPR1 was degraded by the OsCRL4OsDWD1‐mediated ubiquitination system, the phosphodegron‐motif‐mutated NPR1 was partially degraded in the DWD1‐ox protoplasts. This suggests that there might be another degradation process for OsNPR1. Taken together, these results indicate that OsDWD1 regulates OsNPR1 protein levels in rice to suppress the untimely activation of immune responses.
Significance Statement
NPR1 (non‐expresser of pathogenesis‐related gene 1), master regulator in plant immunity and systemic acquired resistance, was regulated by a ubiquitin‐proteasome system (UPS) that has been well studied in the model plant Arabidopsis. In this study, we discovered that Oryza sativa CRL4‐DDB binding WD1 (OsDWD1) was a substrate receptor of the CRL4 complex and that OsNPR1 could be targeted and degraded by the OsDWD1‐mediated ubiquitination system.
When designing this trial, there was no evidence that salvage chemotherapy (SLC) in advanced gastric cancer (AGC) resulted in substantial prolongation of survival when compared with best supportive ...care (BSC). However, SLC is often offered to pretreated patients with AGC for anecdotal reasons.
Patients with AGC with one or two prior chemotherapy regimens involving both fluoropyrimidines and platinum and with an Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned in a ratio of 2:1 to SLC plus BSC or BSC alone. Choice of SLC-either docetaxel 60 mg/m(2) every 3 weeks or irinotecan 150 mg/m(2) every 2 weeks-was left to the discretion of investigators. Primary end point was overall survival (OS).
Median OS was 5.3 months among 133 patients in the SLC arm and 3.8 months among 69 patients in the BSC arm (hazard ratio, 0.657; 95% CI, 0.485 to 0.891; one-sided P = .007). OS benefit for SLC was consistent in most of the prospectively defined subgroups, including age, PS, number of prior treatments, metastatic sites, hemoglobin levels, and response to prior chemotherapy. SLC was generally well tolerated, and adverse events were similar in the SLC and BSC arms. We found no median OS difference between docetaxel and irinotecan (5.2 v 6.5 months; P = .116).
To our knowledge, this is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients, SLC is tolerated and significantly improves OS when added to BSC.
In recent winters, there have been repeated observations of extreme warm and cold spells in the midlatitude countries. This has evoked questions regarding how winter temperature extremes are induced. ...In this study, we demonstrate that abnormally warm winter weather in East Asia can drive the onset of extremely cold weather in North America approximately one week forward. These seesawing extremes across the basin are mediated by the North Pacific Oscillation (NPO), one of the recurrent atmospheric patterns over the North Pacific. Budget analysis of the quasigeostrophic geopotential tendency equation shows that intense thermal advection over East Asia is able to trigger the growth of the NPO. Vorticity fluxes associated with the upper-level stationary trough then strengthen and maintain the NPO against thermal damping following the onset of the NPO. Differential diabatic heating accompanied by changes in circulation also positively contribute to the growth and maintenance of the NPO. These results imply that recurrent cold extremes, seemingly contrary to global warming, may be an inherent feature resulting from strengthening warm extremes.
•Assess Frequency and risk of human intrusion into a geological repository.•Consider a time-dependent drilling probability in a new model for resource exploration.•Human intrusion becomes vigorous ...for demands of resource explorations in the long-term.•Human intrusion is mitigated by enforcement of regulation and continuous knowledge during early time.•Reduced average radiotoxicity is effective to diminish the risk than reduced volume.
Inadvertent human intrusion into a geological repository for radioactive waste is an incident of low frequency but high consequence. Until now, many studies have considered the frequency of deep borehole drilling for resource explorations in the site of the repository as a time-independent variable. However, future activities and technology of the human race will not be the same as today. Therefore, this study develops a new Markov chain model to estimate the frequency of human intrusion using time-dependent drilling frequencies based on the statistics of oil and gas exploration worldwide. The results showed that the frequency of human intrusion during the early time period is substantially reduced. After a few hundred years, the frequency steadily increases and approaches the value of the time-independent model. The low frequency during the early time period is attributed to enforcement of regulation, continuous knowledge of repository, and low utility of repository area. As these effects disappear, the frequency rapidly increases due to the future demand of resource exploration, which is a significant factor in increasing the risk of human intrusion. In addition, the reduction of average radiotoxicity in final waste is effective in reducing the risk, while the reduction of waste volume is insignificant for the frequency of human intrusion in the long-term.
Spent nuclear fuel in a geological repository could be an easily accessible source of Pu for state and non-state proliferators after the level of radioactivity significantly decreases in the long ...term. Such concerns have been continuously raised, but little systematic analysis has been conducted to compare costs and benefits of long-term safeguards to protect Pu in spent nuclear fuel in a final repository. A system thinking model combined with game theory was developed to evaluate the costs and benefits of safeguards of the final repository. In this analysis, the safeguards system is considered as a strategic game between two competing players – a proliferation player and a safeguards player. Detailed data, such as drilling rates and costs, are carefully obtained from real world industrial applications. The costs of safeguards are predicted from the data of commercial satellite monitoring. The model is applied to two potential proliferation scenarios. One is the construction of a clandestine access tunnel using a tunnel boring machine. The other one is chemical extraction through drilling of a vertical deep borehole. The calculated costs of long-term safeguards are mapped for various decisions of the proliferation player and the safeguards player to suggest the optimized approach for the long-term safeguards of the final repository.
•Costs and benefits were analyzed for long-term safeguards of a final repository.•Develop proliferation scenarios of a closed repository using historical data.•Combine a game theory with a system thinking model for decision making.•Show the applicability of the model by finding optimum point of a case study.•Consider the balance between safeguards costs and social security of nuclear energy.
The aim of this prospective phase II study was to evaluate the efficacy and safety of biweekly docetaxel plus androgen-deprivation therapy (ADT) in patients with metastatic castration-naïve prostate ...cancer (mCNPC).
Patients with histologically-proven, previously-untreated mCNPC received ADT plus docetaxel, 40 mg/m
. Docetaxel was repeated every 2 weeks, up to 12 cycles. Endpoints included castration-resistant prostate cancer (CRPC)-free survival, prostate-specific antigen (PSA) response, and safety.
A total of 42 patients were registered and analyzed for final outcomes. Of the 42 patients, 36 (86%) completed the 12 planned cycles of docetaxel plus ADT. During a median follow up of 25 months, all but two patients (95%) achieved a PSA response with a nadir PSA level of 0.42 ng/ml (range 0.01-1280.87). The median CRPC-free survival was 26.4 months (95% confidence interval CI 20.9-32.0) with a one-year CRPC-free rate of 79% (33 patients, 95% CI 66-91). Multivariable analysis revealed that the performance status of the Eastern Cooperative Oncology Group 0 was independently associated with longer CRPC-free survival (hazard ratio HR 0.27, 95% CI 0.07-0.99). The most common adverse events of any grade were anemia (95%), followed by nail changes (33%), fatigue (29%), and oral mucositis (26%). Severe (grade 3 or higher) adverse events were infrequent: pneumonitis (n = 2), diarrhea (n = 1), and neutropenia (n = 1).
Our results suggest that biweekly docetaxel plus ADT is feasible, and clinical efficacy does not seem to be compromised compared to a standard triweekly docetaxel 75 mg/m
plus ADT regimen.
•Frequency and risk of human intrusion into a geological repository are assessed.•Dynamic Monte Carlo model is developed to incorporate various factors increasing or decreasing the risk of human ...intrusion human intrusion.•Regulatory enforcement, knowledge, depth and area of repository are mitigating factors.•Demand of groundwater and utilization of surface above repository are factors enhancing the risk of human intrusion.•Reduced radiotoxicity concentration of a radioactive waste is effective to diminish the risk of human intrusion than reduced area or increased depth of repository.
Future human intrusion into a geological repository for spent nuclear fuels and radioactive waste is a safety case that inherently involves a high uncertainty, especially in areas with a high population density. The uncertainty associated with inadvertent human intrusion needs to account for the complexity of various conceivable circumstances with the long-term evolution of society or technology. In this study, a new dynamic Monte Carlo model is developed to properly incorporate the potential future human intrusion frequency, which has never been performed in past studies. The developed model for inadvertent deep groundwater well drilling into a repository focuses on the assessment of the quantitative effects of factors mitigating or enhancing future human intrusion risk. Assuming the current groundwater well depth distribution in the Gyeongsangnam-do region of the Republic of Korea, the future human intrusion frequency is estimated to be 5.89×10-41/yr for a repository with a depth of 500 m and a hypothetical area of 5.27×10-1km2. The model predicts that the frequency may reach up to 2.18×10-31/yr as the depth of a groundwater well increases in the future, as expected from the data trending performed in this study. A sensitivity analysis shows that a proper design can suppress the frequency, which increases positively with the repository area and negatively with the depth of the repository. However, mitigation by a repository design tends to be weakened as the well depth distribution increases. Since the average well depth increases with time, the mitigation effects achieved by reducing the area or increasing the depth of a repository may not be effective against the current expectation. In this case, the most reliable approach for minimizing future human intrusion risk will be a reduction in the radiotoxicity concentration of the waste.
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