Sodium transporters play key roles in plant tolerance to salt stress. Here, we report that a member of the High-Affinity K⁺ Transporter (HKT) family, OsHKT1;1, in rice (Oryza sativa'Nipponbare') ...plays an important role in reducing Na⁺ accumulation in shoots to cope with salt stress. Theoshkt1;1mutant plants displayed hypersensitivity to salt stress. They contained less Na⁺ in the phloem sap and accumulated more Na⁺ in the shoots compared with the wild type.OsHKT1;1was expressed mainly in the phloem of leaf blades and up-regulated in response to salt stress. Using a yeast one-hybrid approach, a novel MYB coiled-coil type transcription factor, OsMYBc, was found to bind to theOsHKT1;1promoter. In vivo chromatin immunoprecipitation and in vitro electrophoresis mobility shift assays demonstrated thatOsMYBcbinds to AAANATNC(C/T) fragments within theOsHKT1;1promoter. Mutation of theOsMYBc-binding nucleotides resulted in a decrease in promoter activity ofOsHKT1;1. Knockout ofOsMYBcresulted in a reduction in NaCl-induced expression ofOsHKT1;1and salt sensitivity. Taken together, these results suggest that OsHKT1;1 has a role in controlling Na⁺ concentration and preventing sodium toxicity in leaf blades and is regulated by theOsMYBctranscription factor.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The purpose of this study was to identify microRNAs (miRNAs) involved in the pathology of colorectal cancer (CRC) liver metastasis and investigate their underlying mechanisms. A total of 39 miRNAs ...were identified to be differentially expressed between 16 primary CRC tissues with liver metastases and 16 CRC tissues without liver metastases from 32 patients by Affymetric miRNA microarrays. A panel of eight miRNAs were confirmed to be significantly and differentially expressed between CRC tissues with and without liver metastases through quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) analysis in the 32 patients. In a validated cohort of 99 CRC patients (44 with and 55 without liver metastases), only miR‐214 was validated to be significantly down‐regulated in CRC with liver metastases, which was associated with an unfavorable prognosis. Ectopic expression of miR‐214 suppressed proliferation, migration, and invasion in vitro, tumor growth and liver metastasis in an in vivo xenograft mouse model, whereas miR‐214 knockdown promoted proliferation, migration, and invasion in CRC cell lines. Further studies indicated that fibroblast growth factor receptor 1 (FGFR1) was a potential target of miR‐214. Restoring miR‐214 expression in CRC cells decreased endogenous FGFR1 messenger RNA (mRNA) and protein levels. FGFR1 knockdown mimicked the tumor suppressive effect of miR‐214 on CRC cells, while reintroduction of FGFR1 abolished the tumor suppressive effect of miR‐214 on CRC cells. Moreover, miR‐214 expression levels were inversely correlated with FGFR1 in CRC patients. Conclusion: Down‐regulation of miR‐214 expression was correlated with increased FGFR1 expression levels, which may contribute to increased CRC liver metastasis. miR‐214 may serve as a potential marker to predict survival, and the miR‐214‐FGFR1 axis may be a therapeutic target in CRC patients. (Hepatology 2014;60:598–609)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A method for the construction of the indane skeleton through palladium‐catalyzed ring‐opening diarylation of Cyclobutanols with aryl 1,2‐dihalides has been described. The ring‐expansion reaction ...involves β‐carbon elimination of Cyclobutanols and subsequent α‐carbon arylation of ketone to give 2‐acylindanes in 42–93% yields.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Exposure of Lead (Pb), a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP) as well as hippocampal neuronal injury. ...Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks) caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cancer metastasis, a leading cause of death in patients, is associated with aberrant expression of epigenetic modifiers, yet it remains poorly defined how epigenetic readers drive metastatic growth ...and whether epigenetic readers are targetable to control metastasis. Here, we report that bromodomain-containing protein 4 (BRD4), a histone acetylation reader and emerging anticancer therapeutic target, promotes progression and metastasis of gastric cancer. The abundance of BRD4 in human gastric cancer tissues correlated with shortened metastasis-free gastric cancer patient survival. Consistently, BRD4 maintained invasiveness of cancer cells
and their dissemination at distal organs
. Surprisingly, BRD4 function in this context was independent of its putative transcriptional targets such as MYC or BCL2, but rather through stabilization of Snail at posttranslational levels. In an acetylation-dependent manner, BRD4 recognized acetylated lysine 146 (K146) and K187 on Snail to prevent Snail recognition by its E3 ubiquitin ligases FBXL14 and β-Trcp1, thereby inhibiting Snail polyubiquitination and proteasomal degradation. Accordingly, genome-wide transcriptome analyses identified that BRD4 and Snail regulate a partially shared metastatic gene signature in gastric cancer cells. These findings reveal a noncanonical posttranscriptional regulatory function of BRD4 in maintaining cancer growth and dissemination, with immediate translational implications for treating gastric metastatic malignancies with clinically available bromodomain inhibitors. SIGNIFICANCE: These findings reveal a novel posttranscriptional regulatory function of the epigenetic reader BRD4 in cancer metastasis via stabilizing Snail, with immediate translational implication for treating metastatic malignancies with clinically available bromodomain inhibitors. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/19/4869/F1.large.jpg.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Prognosis is often unfavorable. In this study, the effects of microRNA‐802 (miR‐802) on HCC progression were assessed ...in vivo and in vitro. miR‐802 was found to be significantly upregulated in HCC tumor tissue compared to paired adjacent nontumor tissue. In vitro, transfection with a miR‐802 mimic accelerated SMMC‐7721 cellular proliferation, increased accumulation of the cell‐cycle S‐phase cell populations, as well as cell migration. In vivo injection of a miR‐802 agomir promoted HCC proliferation in nude mice. Targets of miR‐802 were predicted by miRWalk, miRanda, RNA22, and Targetscan. By luciferase reporter assay RUNX3 was identified as a direct target of miR‐802. As judged by western blot analysis, RUNX3 was upregulated when miR‐802 was inhibited. These data demonstrate increased miR‐802 expression in patients with HCC and that miR‐802 overexpression promotes tumor cell growth, in a RUNX3‐dependent manner.
Our data demonstrate increased microRNA‐802 (miR‐802) expression in patients with hepatocellular carcinoma and that miR‐802 overexpression promotes tumor cell growth, in a RUNX3‐dependent manner.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Staphylococcus aureus
is a bacterial pathogen that causes food poisoning, various infections, and sepsis. Effective strategies and new drugs are needed to control
S. aureus
associated infections due ...to the emergence and rapid dissemination of antibiotic resistance. In the present study, the antibacterial activity, potential mode of action, and applications of flavonoids from licorice were investigated. Here, we showed that glabrol, licochalcone A, licochalcone C, and licochalcone E displayed high efficiency against methicillin-resistant
Staphylococcus aureus
(MRSA). Glabrol, licochalcone A, licochalcone C, and licochalcone E exhibited low cytotoxicity without hemolytic activity based on safety evaluation. Glabrol displayed rapid bactericidal activity with low levels of resistance development
in vitro
. Meanwhile, glabrol rapidly increased bacterial membrane permeability and dissipated the proton move force. Furthermore, we found that peptidoglycan, phosphatidylglycerol, and cardiolipin inhibited the antibacterial activity of glabrol. Molecular docking showed that glabrol binds to phosphatidylglycerol and cardiolipin through the formation of hydrogen bonds. Lastly, glabrol showed antibacterial activity against MRSA in both
in vivo
and
in vitro
models. Altogether, these results suggest that glabrol is a promising lead compound for the design of membrane-active antibacterial agents against MRSA and can be used as a disinfectant candidate as well.
Glabrol isolated from licorice rapidly kill MRSA
via
the disruption of the membrane permeability and the proton motive force.
Maintaining Na+/K+ homeostasis is a critical feature for plant survival under salt stress, which depends on the operation of Na+ and K+ transporters. Although some K+ transporters mediating root K+ ...uptake have been reported to be essential to the maintenance of Na+/K+ homeostasis, the effect of K+ long‐distance translocation via phloem on plant salt tolerance remains unclear. Here, we provide physiological and genetic evidence of the involvement of phloem‐localized OsAKT2 in rice salt tolerance. OsAKT2 is a K+ channel permeable to K+ but not to Na+. Under salt stress, a T‐DNA knock‐out mutant, osakt2 and two CRISPR lines showed a more sensitive phenotype and higher Na+ accumulation than wild type. They also contained more K+ in shoots but less K+ in roots, showing higher Na+/K+ ratios. Disruption of OsAKT2 decreases K+ concentration in phloem sap and inhibits shoot‐to‐root redistribution of K+. In addition, OsAKT2 also regulates the translocation of K+ and sucrose from old leaves to young leaves, and affects grain shape and yield. These results indicate that OsAKT2‐mediated K+ redistribution from shoots to roots contributes to maintenance of Na+/K+ homeostasis and inhibition of root Na+ uptake, providing novel insights into the roles of K+ transporters in plant salt tolerance.
In Oryza sativa, a Shaker K+ channel, OsAKT2 mediates K+ redistribution from shoots to roots, contributing to maintenance of Na+/K+ homeostasis and inhibition of root Na+ uptake under salt stress.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A rhodium-catalyzed decarbonylation/alkyne insertion cascade of phthalimides has been established. The reaction can be carried out in an operationally simple manner and provides expedient access to a ...series of isoquinolones in moderate to good yields. This reaction proceeded through a sequential decarbonylation/alkyne insertion/intramolecular annulation procedure and featured good functional group tolerance, ample substrate scope, and the construction of C-C and C-N bonds in one pot.
Penalty function is well-known for constrained evolutionary optimization. An open question in the penalty function is how to tune the penalty coefficient. This paper proposes an adaptive fuzzy ...penalty method to address this issue, where the coefficient is adjusted at both the individual level and the population level. At the individual level, each individual chooses a penalty coefficient from a predefined domain according to some fuzzy rules. At the population level, the domain of the crisp output is adjusted adaptively by using population information. To enhance the population diversity, an effective mutation scheme is developed. Due to its numerous merits, differential evolution is used to design a search algorithm. By the above processes, a constrained optimization evolutionary algorithm called AFPDE is proposed. Since the objective function value and the degree of constraint violation are normalized, AFPDE is less problem-dependent than the seminal work of the fuzzy penalty method. AFPDE introduces a lower penalty value in the early stage of AFPDE while a higher one in the later stage. Thus, it can escape local optima in the infeasible region. Experiments on three well-known benchmark test sets and two mechanical design problems validate that AFPDE is competitive.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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