Plasticity of Intestinal Epithelium: Stem Cell Niches and Regulatory Signals

The discovery of Lgr5+ intestinal stem cells (ISCs) triggered a breakthrough in the field of ISC research. Lgr5+ ISCs maintain the homeostasis of the intestinal epithelium in the steady state, while these cells are susceptible to epithelial damage induced by chemicals, pathogens, or irradiation. During the regeneration process of the intestinal epithelium, more quiescent +4 stem cells and short-lived transit-amplifying (TA) progenitor cells residing above Lgr5+ ISCs undergo dedifferentiation and act as stem-like cells. In addition, several recent reports have shown that a subset of terminally differentiated cells, including Paneth cells, tuft cells, or enteroendocrine cells, may also have some degree of plasticity in specific situations. The function of ISCs is maintained by the neighboring stem cell niches, which strictly regulate the key signal pathways in ISCs. In addition, various inflammatory cytokines play critical roles in intestinal regeneration and stem cell functions following epithelial injury. Here, we summarize the current understanding of ISCs and their niches, review recent findings regarding cellular plasticity and its regulatory mechanism, and discuss how inflammatory cytokines contribute to epithelial regeneration.     

Re-evaluation of Radiation-Energy Transfer to an Extraction Solvent in a Minor-Actinide-Separation Process Based on Consideration of Radiation Permeability

ABSTRACT

Absorbed-dose estimation is essential for evaluation of the radiation tolerance of minor-actinide-separation processes. We propose a dose-evaluation method based on radiation permeability, with comparisons of heterogeneous structures seen in the solvent-extraction process, such as emulsions forming in the mixture of the organic and aqueous phases. A demonstration of radiation-energy-transfer simulation is performed with a focus on the minor-actinide-recovery process from high-level liquid waste with the aid of the Monte Carlo radiation-transport code PHITS. The simulation results indicate that the dose absorbed by the extraction solvent from alpha radiation depends upon the emulsion structure, and that from beta and gamma radiation depends upon the mixer-settler-apparatus size. Non-negligible contributions of well-permeable gamma rays were indicated in terms of the plant operation of the minor-actinide-separation process.     

Synthesis and Initial Characterization of a Selective,Pseudo-irreversible Inhibitor of Human Butyrylcholinesterase as PET Tracer

The enzyme butyrylcholinesterase (BChE) represents a promising target for imaging probes to potentially enable early diagnosis of neurodegenerative diseases like Alzheimer's disease (AD) and to monitor disease progression in some forms of cancer. In this study, we present the design, facile synthesis, in vitro and preliminary ex vivo and in vivo evaluation of a morpholine-based, selective inhibitor of human BChE as a positron emission tomography (PET) tracer with a pseudo-irreversible binding mode. We demonstrate a novel protecting group strategy for ¹⁸F radiolabeling of carbamate precursors and show that the inhibitory potency as well as kinetic properties of our unlabeled reference compound were retained in comparison to the parent compound. In particular, the prolonged duration of enzyme inhibition of such a morpholinocarbamate motivated us to design a PET tracer, possibly enabling a precise mapping of BChE distribution.     

Cold-start performance of an ammonia-fueled spark ignition engine with an on-board fuel reformer

This work demonstrated the first-ever cold-start operation of an ammonia (NH₃)-fueled four-cylinder spark ignition engine with an on-board fuel reformer, applying autothermal reforming. In this system, an electrically heated NH₃-air mixture was provided to a reforming catalyst and approximately 3 s was found to elapse between the start of engine rotation and the onset of combustion. Stable fast idle operation in conjunction with a cold start was realized with a H₂-to-NH₃ molar ratio of 2:1. Nearly zero NH₃ emissions were achieved during cold start and fast idle until the engine warmed up, by adsorbing unburned NH₃ passing through a three-way catalyst before the catalyst was sufficiently warmed up. The NH₃ adsorption capacity of this system could be regenerated during the engine warm-up when the engine was running under lean conditions.     

Mechanisms of orientational and photoelastic birefringence generation of methacrylates for the design of zero–zero‐birefringence polymers

The intrinsic birefringence Δn⁰ and photoelastic coefficient C of poly(methyl methacrylate), poly(2,2,2‐trifluroethyl methacrylate), poly(phenyl methacrylate), and poly(2,2,3,3,3‐pentafluorophenyl methacrylate) were determined. We categorized these methacrylate polymers into four birefringence‐types, even though their molecular structures differed only by the substituents on the side chains. Based on the results of Δn⁰ and C, novel polymers that exhibit neither orientational nor photoelastic birefringence, i.e., zero–zero‐birefringence polymers, were designed and synthesized by quaternary copolymerization system. Furthermore, we confirmed that the mechanisms of orientational birefringence and photoelastic birefringence generation were different in these methacrylate polymers. The conformation of the repeat unit of the polymers was nearly constant during the generation of orientational birefringence. In contrast, the conformation of the repeat unit of the polymers changed during the generation of photoelastic birefringence in the glassy state. These findings demonstrated the reasonability of evaluating orientational and photoelastic birefringence separately, as well as the adequacy of the classification of polymers into four birefringence‐types. Given these results and the fact that zero–zero‐birefringence polymers could be prepared successfully by four‐birefringence type monomers, we demonstrated the reasonability of the method for designing the zero–zero‐birefringence polymers. POLYM. ENG. SCI., 55:1330–1338, 2015. © 2015 Society of Plastics Engineers     

Evaluation of the Anti-Proliferative Activity of Rare Aldohexoses against MOLT-4F and DU-145 Human Cancer Cell Line and Structure-Activity Relationship of D-Idose

D-Allose (D-All), a C-3 epimer of D-glucose (D-Glc), is a naturally rare monosaccharide, which shows anti-proliferative activity against several human cancer cell lines. Unlike conventional anticancer drugs, D-All targets glucose metabolism and is non-toxic to normal cells. Therefore, it has attracted attention as a unique “seed” compound for anticancer agents. However, the anti-proliferative activities of the other rare aldohexoses have not been examined yet. In this study, we evaluated the anti-proliferative activity of rare aldohexoses against human leukemia MOLT-4F and human prostate cancer DU-145 cell lines. We found that D-All and D-idose (D-Ido) at 5 mM inhibited cell proliferation of MOLT-4F cells by 46 % and 60 %, respectively. On the other hand, the rare aldohexoses at 5 mM did not show specific anti-proliferative activity against DU-145 cells. To explore the structure–activity relationship of D-Ido, we evaluated the anti-proliferative activity of D-sorbose (D-Sor), 6-deoxy-D-Ido, and L-xylose (L-Xyl) against MOLT-4F cells and found that D-Sor, 6-deoxy-D-Ido, and L-Xyl showed no inhibitory activity at 5 mM, suggesting that the aldose structure and the C-6 hydroxy group of D-Ido are important for its activity. Cellular glucose uptake assay and western blotting analysis of thioredoxin-interacting protein (TXNIP) expression suggested that the anti-proliferative activity of D-Ido is induced by inhibition of glucose uptake via TXNIP-independent pathway.     

Comparison of isolation methods using commercially available kits for obtaining extracellular vesicles from cow milk

Extracellular vesicles (EV) are important for delivering biologically active substances to facilitate cell-to-cell communication. Milk-derived EV are widely known because of their potential for immune enhancement. However, procedures for isolating milk-derived EV have not been fully established. To obtain pure milk-derived EV and accurately reveal their function, such procedures must be established. The aim of the present study was to compare methods using commercially available kits for isolating milk-derived EV. Initially, we investigated procedures to remove casein, which is the major obstacle in determining milk-derived EV purity. We separated whey using centrifugation only, acetic acid precipitation, and EDTA precipitation. Then, we isolated milk-derived EV by ultracentrifugation, membrane affinity column, size exclusion chromatography (SEC), polymer-based isolation, or phosphatidylserine-affinity isolation. Using EV count per milligram of protein, which is a good indicator of purity, we determined that acetic acid precipitation was the best method for removing casein. Using nanoparticle tracking analysis, protein quantity analysis, and RNA quantity analysis, we comprehensively compared each isolation method for its purity and yield. We found that SEC-based qEV column (Izon Science) could collect purer milk-derived EV at higher quantities. Thus, a combination of acetic acid precipitation and qEV can effectively isolate high amounts of pure extracellular vesicles from bovine milk.     

Bottom-up synthesis of oxygen-containing carbon materials using a Lewis acid catalyst

Oxygen-containing carbon materials have been studied extensively because of their excellent dispersibility, absorptivity, separability, and supportability of catalysts. However, structural control by existing top-down methods is almost impossible. Our group has demonstrated that phloroglucinol (PG, 1,3,5-trihydroxybenzene) can be a promising raw material to synthesize structurally controlled oxygen-containing carbon materials. In this study, in addition to PG, hexahydroxybenzene (HHB), which has more oxygen and high symmetry, was used as the raw material, and a Lewis acid catalyst, tris (pentafluorophenyl) borane (TPB), was used to enhance the structural control rate and the removability of catalysts from the carbonized samples. The solubility of heat-treated HHB was lower than that of heat-treated PG, but the oxygen content of heat-treated HHB was higher than that of heat-treated PG even at 673 K. By adding TPB to PG, dibenzofuran-like structures formed, and the structural control rate increased up to 93.6%. Besides, the content of fluorine in the catalyst was reduced to 0%, indicating that TPB can be a promising recyclable catalyst to promote the structural control rate of carbonized PG.

Graphical abstract

     

基于GIS空间数据库的三维边坡稳定性分析

结合GIS的空间数据分析功能和改进的Hovland三维边坡稳定分析模型，提出一个全新的基于GIS空间数据库的三维边坡稳定分析模型，假定初始三维滑动面为椭球形，研究采用Monte-Carlo模拟方法搜寻最危险滑动面，全部分析研究程序采用VB和GIS控制软件编制，利用GIS的空间数据处理分析功能，各种可能滑动面所需输入数据可以方便地得到，而且结果也能方便地在数字地图上表示和分类。     

Characteristics of humic substances in the Kuji River waters as determined by high-performance size exclusion chromatography with fluorescence detection

Direct measurement by high-performance size exclusion chromatography with fluorescence detection was applied to the characterization of humic substances in river waters from the Kuji River system, which runs through forest hills and an agricultural plain in Japan. The monitoring wavelength of excitation 320 nm and emission 430 nm corresponds to the fluorescence maxima for aquatic fulvic acid. Chromatograms of the river waters showed four peaks; each peak position was in good agreement among these samples. Peak height ratios for the samples from the upstream Kuji River and its tributaries were different from those of the midstream and downstream sections of the Kuji River, which may reflect differences in the characteristics of humic substances and other organic materials supplied from soil to river.