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.     

Measurement of vertical and horizontal vibrations of a probe for acoustic evaluation of food texture

Two‐dimensional (vertical and horizontal) vibrations of a wedge‐type probe upon food rupture were evaluated separately using two accelerometers placed perpendicular to a guide rod of a swing‐arm device for texture evaluation of the flesh of three varieties of apples and three types of potato chips. Voltage signals from the accelerometers were filtered using a half‐octave band‐pass filter. The energy texture index (ETI), based on kinetic energy of the vertical or horizontal probe vibrations, was calculated over low to high frequency bands (no. 1–21). The spectra for the flesh of the three varieties of apples included two common peaks for vertical ETI at band no. 11 (1,120–1,600 Hz) and 19 (17,920–25,600 Hz) and horizontal ETI at band no. 1 (0–10 Hz) and 15 (4,480–6,400 Hz). The spectra for the three types of potato chips had a common ETI peak at band no. 11 (1,120–1,600 Hz) for horizontal ETI and at no. 15 (4,480–6,400 Hz) for vertical ETI. The three apple varieties gave rise to different intensities of vertical and horizontal ETIs while the two peaks were maintained. The thick potato chip type had higher vertical and horizontal ETIs than the thin and soft varieties in most bands; however, the thin type had the highest vertical ETIs only in lower bands (0–200 Hz). The soft type had the lowest vertical and horizontal ETI. The above results suggest that different food textures can be distinguished by two‐dimensional vibration analyses of probe insertion into a food sample based on frequency bands.     

Large-scale genome reorganization in Saccharomyces cerevisiae through combinatorial loss of mini-chromosomes

A highly efficient technique, termed PCR-mediated chromosome splitting (PCS), was used to create cells containing a variety of genomic constitutions in a haploid strain of Saccharomyces cerevisiae. Using PCS, we constructed two haploid strains, ZN92 and SH6484, that carry multiple mini-chromosomes. In strain ZN92, chromosomes IV and XI were split into 16 derivative chromosomes, seven of which had no known essential genes. Strain SH6484 was constructed to have 14 mini-chromosomes carrying only non-essential genes by splitting chromosomes I, II, III, VIII, XI, XIII, XIV, XV, and XVI. Both strains were cultured under defined nutrient conditions and analyzed for combinatorial loss of mini-chromosomes. During culture, cells with various combinations of mini-chromosomes arose, indicating that genomic reorganization could be achieved by splitting chromosomes to generate mini-chromosomes followed by their combinatorial loss. We found that although non-essential mini-chromosomes were lost in various combinations in ZN92, one mini-chromosome (18kb) that harbored 12 genes was not lost. This finding suggests that the loss of some combination of these 12 non-essential genes might result in synthetic lethality. We also found examples of genome-wide amplifications induced by mini-chromosome loss. In SH6484, the mitochondrial genome, as well as the copy number of genomic regions not contained in the mini-chromosomes, was specifically amplified. We conclude that PCS allows for genomic reorganization, in terms of both combinations of mini-chromosomes and gene dosage, and we suggest that PCS could be useful for the efficient production of desired compounds by generating yeast strains with optimized genomic constitutions.     

Blood Pressure Elevation of Tubular Specific (P)RR Transgenic Mice and Lethal Tubular Degeneration due to Possible Intracellular Interactions between (P)RR and Alternative Renin Products

The prorenin/renin receptor ((P)RR) is a multifunctional protein that is widely distributed in various organs. Despite intensive research for more than 20 years, this receptor has not been fully characterized. In this study, we generated mice overexpressing the tubular epithelial (P)RR gene ((P)RR-TG mice) to test the previously reported functional role of (P)RR by Ramkumar et al. in 2015 using tubular specific (P)RR KO mice. (P)RR-TG mice were maintained and analyzed in individual metabolic cages and were administered angiotensin II blocker (ARB), direct renin inhibitor (DRI), and bafilomycin, that is, vacuolar ATPase (V-ATPase) antagonist. (P)RR-TG mice were hypertensive and had alkalized urine with lower osmolality and Na⁺ excretion. ARB and DRI, but not bafilomycin, concurrently decreased blood pressure. Bafilomycin acidized urine of (P)RR-TG mice, or equivalently this phenomenon restored the effect of overexpressed transgene, suggesting that (P)RR functioned as a V-ATPase in renal tubules. Afterall, (P)RR-TG mice were mated with alternative renin transgenic mice (ARen2-TG), which we identified as intracellular renin previously, to generate double transgenic mice (DT-TG). Lethal renal tubular damage was observed in DT-TG mice, suggesting that intracellular renin may be a ligand for (P)RR in tubules. In summary, (P)RR did not substantially affect the tissue renin-angiotensin system (RAS) in our model of tubular specific (P)RR gene over-expression, but alternative intracellular renin may be involved in (P)RR signaling in addition to conventional V-ATPase function. Further investigations are warranted.     

Experimental investigation and numerical modeling of chloride penetration and calcium dissolution in saturated concrete

Chloride penetration and calcium dissolution have been investigated for a saturated concrete after exposure to a 0.5 mol/L NaCl solution for a period of up to 3150 days. Simultaneous ion transport model (SiTraM) that allows the transport of chloride and calcium ions to be simultaneously simulated in a hydrated cement system has been used to verify the experimental results.Self-compacting concrete (SCC) with a water to cement ratio of 0.3 resulted in a limited chloride penetration depth while the calcium dissolution was also reduced within the near surface zone. Increased unit water content for normal concrete resulted in higher chloride penetration depth and larger dissolution front of Ca(OH)₂ regardless of having the same water to cement ratio.It was revealed that the SiTraM can predict the profiles of chloride and calcium for self-compacting concrete. It was also found that the primary factor to control chloride penetration front and the dissolution front of Ca(OH)₂ was the pore structure characteristic of concrete.     

Quantitative Elemental Analysis of a Single Cell by Using Inductively Coupled Plasma-Mass Spectrometry in Fast Time-Resolved Analysis Mode

The elemental composition of a single yeast, green alga, or red blood cell (RBC) was precisely determined by using inductively coupled plasma-mass spectrometry (ICP-MS) operating in fast time-resolved analysis (TRA) mode. The technique is known as single-cell (SC)-ICP-MS. Phosphorus, sulfur, magnesium, zinc, and iron were detected in the three types of cell. The elemental composition of yeast and green alga obtained by SC-ICP-MS was consistent with results obtained from conventional ICP-MS measurements following acid digestion of the cells. Slight differences were found in the measured values between SC-ICP-MS and the conventional ICP-MS results for RBC. However, the SC-ICP-MS results for S and Fe in RBC were closer to the estimated values for these elements that were calculated from the level of hemoglobin in RBCs. The data suggest that SC-ICP-MS is suitable for the analysis of various cell types, namely, fungus, plant, and animal cells.     

Genotype and phenotype of severe mitochondrial cardiomyopathy: a recipient of heart transplantation and the genetic control

Comprehensive analyses of mitochondrial (mt)DNA of a recipient of heart transplantation at age 7 because of severe cardiomyopathy revealed three germ line point mutations, each one in the 12S rRNA gene, in the CO1 gene and in the cytochrome b gene, respectively. As the somatic mutation, extensive fragmentation of mtDNA associated with 212 kinds of deletions was detected in contrast to 5 kinds in an age-matched negative control. A recipient's positive control having almost the same base-substitutions and mutations with the recipient except one in the CO1 gene also developed severe cardiomyopathy died at age 20. The close relation between phenotype and mtDNA genotype provides the basis of our understanding of cell death and premature ageing.     

Ketones from carboxylic acids over supported magnesium oxide and related catalysts

Silica-supported alkaline earth oxides revealed excellent activity to convert acetic acid selectively into acetone in a vapor-phase fixed-bed flow system. Acetone was obtained through the cyclic formation of alkaline earth acetate followed by decomposition. Magnesium oxide should be supported on the silica surface without formation of magnesium silicate, which was inactive for the present reaction. Attempted syntheses of benzophenone and acetophenone are also described.