The molecular interaction of Fas and FAP-1. A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis

Fas (APO-1/CD95), which is a member of the tumor necrosis factor receptor superfamily, is a cell surface receptor that induces apoptosis. A protein tyrosine phosphatase, Fas-associated phosphatase-1 (FAP-1), that was previously identified as a Fas binding protein interacts with the C-terminal 15 amino acids of the regulatory domain of the Fas receptor. To identify the minimal region of the Fas C-terminal necessary for binding to FAP-1, we employed an in vitro inhibition assay of Fas/FAP-1 binding using a series of synthetic peptides as well as a screen of random peptide libraries by the yeast two-hybrid system. The results showed that the C-terminal three amino acids (SLV) of human Fas were necessary and sufficient for its interaction with the third PDZ (GLGF) domain of FAP-1. Furthermore, the direct cytoplasmic microinjection of this tripeptide (Ac-SLV) resulted in the induction of Fas-mediated apoptosis in a colon cancer cell line that expresses both Fas and FAP-1. Since t(S/T)X(V/L/I) motifs in the C termini of several other receptors have been shown to interact with PDZ domain in signal transducing molecules, this may represent a general motif for protein-protein interactions with important biological functions.     

Discordant prolongation of the refractory period and repolarization time by a class III agent, E4031, in the healing phase of myocardial infarction

One hundred and ninety-eight adolescents and their mothers (N = 189) and fathers (N = 136) participated in a 4-year longitudinal study. Adolescent problem behaviour was assessed by the Youth Self-Report (YSR) and the Child Behavior Checklist (CBCL). In addition, parental stress and marital adjustment were determined. Results showed that mothers and fathers showed high agreement, especially about their daughters, whereas parents and adolescents showed little agreement. Agreement was higher for internalising than for externalising behaviours. In general, adolescents reported more symptomatology than their parents did. However, mothers' ratings of their children's behaviours were significantly correlated with adolescents' self-ratings, but fathers' ratings were not. Statistical tests of correlations showed that mothers experiencing stress caused by marital problems perceived more problem behaviours in their children. Fathers' perceptions were relatively unaffected by personal adjustment. However, poor marital adjustment perceived by both parents showed a significant negative relation to adolescent externalising problem behaviour.     

一种适合于电子政务中业务处理的过程模型

目前，电子政务系统一般通过业务过程模型支持电子政务业务处理，而当前已有的业务过程模型在灵活性和安全性方面尚存在不足。为此，提出了一种适合于电子政务中业务处理的过程模型，它将多变的业务规则从过程流中分离出来，通过耦合机制实现业务规则与过程流的结合。该模型简化了过程流的定义，使过程流的变更相对容易，而且可以在不改变过程流的情况下独立、便捷地维护业务规则，确保业务处理的安全性。最后给出了一个使用该模型的电子政务业务处理应用实例。     

Possible Involvement of the Upregulation of ΔNp63 Expression Mediated by HER2-Activated Aryl Hydrocarbon Receptor in Mammosphere Maintenance

Cancer stem cells (CSCs) contribute to the drug resistance, recurrence, and metastasis of breast cancers. Recently, we demonstrated that HER2 overexpression increases mammosphere formation via the activation of aryl hydrocarbon receptor (AHR). In this study, the objective was to identify the mechanism underlying mammosphere maintenance mediated by HER2 signaling-activated AHR. We compared the chromatin structure of AHR-knockout (AHRKO) HER2-overexpressing MCF-7 (HER2-5) cells with that of wild-type HER2-5 cells; subsequently, we identified TP63, a stemness factor, as a potential target gene of AHR. ΔNp63 mRNA and protein levels were higher in HER2-5 cells than in HER2-5/AHRKO cells. Activation of HER2/HER3 signaling by heregulin treatment increased ΔNp63 mRNA levels, and its induction was decreased by AHR knockdown in HER2-5 cells. The results of the chromatin immunoprecipitation assay revealed an interaction between AHR and the intronic region of TP63, which encodes ΔNp63. A luciferase reporter gene assay with the intronic region of TP63 showed that AHR expression increased reporter activity. Collectively, our findings suggest that HER2-activated AHR upregulates ΔNp63 expression and that this signaling cascade is involved in CSC maintenance in HER2-expressing breast cancers.     

一种分离业务规则的灵活业务过程建模方法

针对动态环境中业务应用的不断变化,将易变的业务逻辑从过程控制结构中分离,并且通过业务规则的声明性表达式描述,由此构建了业务过程模型BPM4DBL(Business Process Model for Dynamic Business Logic)。在建立规则元素的模型定义后,给出了业务规则的定义、分类和可执行语言描述,最后给出一个BPM4DBL的具体应用实例。     

Extraction of Trivalent Rare Earths and Minor Actinides from Nitric Acid with N,N,N’,N’-Tetradodecyldiglycolamide (TDdDGA) by Using Mixer-Settler Extractors in a Hot Cell

Single-stage batch experiments to reveal the extraction properties of N,N,N’,N’-tetradodecyldiglycolamide (TDdDGA) for Y, La, Eu, Nd, and Am in nitric acid were carried out. The distribution ratios of Y, Eu, Nd, and Am exceeded 10 when the nitric acid concentration was 1–2 mol/dm³ (M), and the distribution ratio of La was 5.5 when the nitric acid concentration was 2 M. A continuous counter-current experiment using 0.1 M TDdDGA diluted with n-dodecane was performed using mixer-settler extractors installed in a hot cell. Nitric acid with a concentration of 2.1 M containing minor actinides (MAs: Am and Cm), rare earths (REs: Y, La, Nd, and Eu), and other fission products (Sr, Cs, Zr, Mo, Ru, Rh, and Pd) was fed to the extractor. TDdDGA effectively extracted MAs and REs from the feed, while other fission products were barely extracted. The extracted MAs and REs were back-extracted by bringing them in contact with 0.02 M nitric acid, and they were collected as the MA–RE fraction. The results indicated that more than 98% of Am and Cm in the feed were recovered in the MA–RE fraction. The proportions of Y, La, Nd, and Eu in the MA–RE fraction were 94.0%, 99.9%, 99.9%, and 86.9%, respectively.     

Stabilizing effect of the cyclodextrins additive to spray-dried particles of curcumin/polyvinylpyrrolidone on the supersaturated state of curcumin

Although curcumin is considered to have various therapeutic effects, its use as a functional food or supplement is restricted owing to its low water solubility and bioavailability. To increase the solubility of curcumin in water, the use of polyvinylpyrrolidone (PVP) and vinylpyrrolidone-vinyl acetate copolymers with a pyrrolidone skeleton was noted to be promising. In particular, the bi-component formulations of curcumin/PVP prepared through spray drying exhibited an amorphous state in powder X-ray diffraction observations and temporally increased the apparent solubility of curcumin to over 5000 times that of untreated curcumin; nevertheless, after 24 h, the solubility decreased owing to the unstable supersaturated state of curcumin. The addition of α-cyclodextrin (α-CyD) in the bi-component curcumin/PVP formulation helped maintain the supersaturated state of curcumin, whereas the addition of β- and γ-CyD led to the collapse of the supersaturated state. The addition of α-CyD can likely help inhibit the nucleation and crystal growth of curcumin, through the interaction among the solubilized units of curcumin/PVP and α-CyD.     

Effects of supercritical carbon dioxide treatment on the morphology of poly(l‐lactide)

Synthetic l ‐lactide random copolymers can be employed as controlled release materials when prepared using supercritical carbon dioxide (scCO₂), since they are biodegradable via hydrolysis. To determine the effects of thermal properties on polymer performance following scCO₂ processing, three types of poly(l ‐lactide) having different properties were assessed. The T_m of one poly(l ‐lactide) sample (H‐100) was found to be approximately 170 °C over the processing pressure range from 8 to 18 MPa, while a second sample (H‐440) also showed a constant value of approximately 152 °C. In contrast, the poly(l ‐lactide) REVODE exhibited a T_m of 146 °C prior to processing but a higher value of 147 °C following treatment at 8 MPa. Unlike the H‐100 and H‐440, the T_m value of the REVODE tended to decrease with increasing pressure. The T_g values increased greatly under mild conditions of 8 MPa pressure and a temperature of 40 °C. In particular, the T_g values for the H‐440 and REVODE increased by 4 °C and 5 °C, respectively. All T_g values were lowest at 12 MPa and increased with increasing processing pressure, although the effect of processing temperature was minimal. The Χ_{c DSC} of the H‐100 was 18% initially but increased to 20% upon scCO₂ processing at 40 °C and 14 MPa, and showed further increases at higher processing temperatures. Although the relationship between processing temperature and Χ_{c DSC} values for the H‐440 showed the same trend as observed with the H‐100, a different trend was seen for the REVODE. The Χ_{c XRD} values obtained from the XRD analyses differed from the values generated by DSC analysis, and showed a maximum degree of crystallinity following processing at 80 °C both with and without scCO₂ treatment. ATR FT‐IR analyses identified peaks due to semicrystalline regions in poly(l ‐lactide) samples treated with scCO₂, even when applying low temperatures. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44006.     

Serum Amyloid A3 Promoter-Driven Luciferase Activity Enables Visualization of Diabetic Kidney Disease

The early detection of diabetic nephropathy (DN) in mice is necessary for the development of drugs and functional foods. The purpose of this study was to identify genes that are significantly upregulated in the early stage of DN progression and develop a novel model to non-invasively monitor disease progression within living animals using in vivo imaging technology. Streptozotocin (STZ) treatment has been widely used as a DN model; however, it also exhibits direct cytotoxicity to the kidneys. As it is important to distinguish between DN-related and STZ-induced nephropathy, in this study, we compared renal responses induced by the diabetic milieu with two types of STZ models: multiple low-dose STZ injections with a high-fat diet and two moderate-dose STZ injections to induce DN. We found 221 genes whose expression was significantly altered during DN development in both models and identified serum amyloid A3 (Saa3) as a candidate gene. Next, we applied the Saa3 promoter-driven luciferase reporter (Saa3-promoter luc mice) to these two STZ models and performed in vivo bioluminescent imaging to monitor the progression of renal pathology. In this study, to further exclude the possibility that the in vivo bioluminescence signal is related to renal cytotoxicity by STZ treatment, we injected insulin into Saa3-promoter luc mice and showed that insulin treatment could downregulate renal inflammatory responses with a decreased signal intensity of in vivo bioluminescence imaging. These results strongly suggest that Saa3 promoter activity is a potent non-invasive indicator that can be used to monitor DN progression and explore therapeutic agents and functional foods.