AbstractWe prepared 81 samples of sweetened viscous solutions and gels with agar concentrations ranging from 0.025% to 0.60% and compared their sweetness intensities to reference solutions without agar. Sweetened viscous solutions containing agar showed significantly higher sweetness intensity in six solutions containing D‐glucose, three solutions containing sucrose, and four solutions containing D‐sorbitol compared to the reference solutions. Notably, some sweetened viscous solutions with extremely low viscosity showed higher sweetness intensity than the reference solution, which is a novel finding. Sweet samples containing agar showed significantly lower sweetness intensity than the reference solution in 15 samples containing D‐glucose, 17 samples containing sucrose, and 15 samples containing D‐sorbitol, supporting previous theories. We performed a simple regression analysis on the sweetness intensity of viscous solutions and gels containing agar and their physical properties. Our results showed a strong correlation between sweetness intensity and physical properties. These findings suggest that as sweetness intensity decreases, physical properties tend to increase.Practical ApplicationsTo prevent noncommunicable diseases such as diabetes, it is recommended to practice carbohydrate restriction and reduce the consumption of sweet foods. In this study, upon being offered extremely low‐viscosity sweetened solutions, we anticipate perceiving a slightly stronger sweetness and an increased sense of satisfaction in contrast to tasting sweetened aqueous solutions without viscosity. These findings hold the potential to provide pioneering insights into the interplay between taste and texture for entities such as food manufacturers. They could facilitate applications designed to elevate the quality of health‐conscious food production.

Reticular dysgenesis (RD) is a rare genetic disease caused by gene mutations in the ATP:AMP phosphotransferase, adenylate kinase 2 (AK2). Patients with RD suffer from severe combined immunodeficiency with neutrophil maturation arrest. Although hematopoietic stem cell transplantation can be a curative option, it is invasive, and complications of agranulocytosis-induced infection worsen the prognosis. Here, we report that the use of UK-5099, an inhibitor of the mitochondrial pyruvate carrier (MPC), on hemo-angiogenic progenitor cells (HAPCs) derived from AK2-deficient induced pluripotent stem cells improved neutrophil maturation. Reactive oxygen species (ROS) levels in AK2-deficient HAPCs remained unchanged throughout all experiments, implying that UK-5099 improved the phenotype without affecting ROS levels. Overall, our results suggest that the MPC is a potential therapeutic target for the treatment of neutrophil maturation defects in RD.

The precise formation of mineralized dental tissues such as enamel and/or dentin require tight transcriptional control of the secretion of matrix proteins. Here, we have investigated the transcriptional regulation of the second most prominent enamel matrix protein, enamelin, and its regulation through the major odontogenic transcription factor, MSX2. Using in vitro and in vivo approaches, we identified that (a) Enam expression is reduced in the Msx2 mouse mutant pre-secretory and secretory ameloblasts, (b) Enam is an early response gene whose expression is under the control of Msx2, (c) Msx2 binds to Enam promoter in vitro, suggesting that enam is a direct target for Msx2 and that (d) Msx2 alone represses Enam gene expression. Collectively, these results illustrate that Enam gene expression is controlled by Msx2 in a spatio-temporal manner. They also suggest that Msx2 may interact with other transcription factors to control spatial and temporal expression of Enam and hence amelogenesis and enamel biomineralization.

【方法】あらかじめ単独試料のにおいを学習させ，その際ににおいに誘導される情動 (快・不快) をビジュアルアナログスケール (VAS) で評価させた。その後に，2種混合のにおいの同定検査を実施し，提示した6種類の中から2種類のにおいを選択させた。その際に混合のにおいに誘導される情動 (快・不快) もVASで評価させ，単独試料の評価と比較した。

Mitochondrial ATP production plays an important role in most cellular activities, including growth and differentiation. Previously we reported that Adenylate kinase 2 (AK2) is the main ADP supplier in the mitochondrial intermembrane space in hematopoietic cells, especially in the bone marrow. AK2 is crucial for the production of neutrophils and T cells, and its deficiency causes reticular dysgenesis. However, the relationship between ADP supply by AK2 and neutrophil differentiation remains unclear. In this study, we used CRISPR/Cas9 technology to establish two heterozygous AK2 knock-out HL-60 clones as models for reticular dysgenesis. Their AK2 activities were about half that in the wild-type (WT). Furthermore, neutrophil differentiation was impaired in one of the clones. In silico analysis predicted that the obtained mutations might cause a structural change in AK2. Time course microarray analysis of the WT and mutants revealed that similar gene clusters responded to all-trans retinoic acid treatment, but their expression was lower in the mutants than in WT. Application of fructose partially restored neutrophil differentiation in the heterozygous knock-out HL-60 clone after all-trans retinoic acid treatment. Collectively, our study suggests that the mutation of N-terminal region in AK2 might play a role in AK2-dependent neutrophil differentiation and fructose could be used to treat AK2 deficiency.

Glucosylceramide is the primary molecule of glycosphingolipids, and its metabolic regulation is crucial for life. Defects in the catabolizing enzyme, glucocerebrosidase (GCase), cause a lysosomal storage disorder known as Gaucher disease. However, the genetic regulation of GCase has not been fully understood. Here we show the redefined structure of the GCase coding gene (GBA), and clarify the regulatory mechanisms of its transcription and translation. First, alternative uses of the two GBA gene promoters were identified in fibroblasts and HL60-derived macrophages. Intriguingly, both GBA transcripts and GCase activities were induced in macrophages but not in neutrophils. Second, we observed cap-independent translation occurs via unique internal ribosome entry site activities in first promoter-driven GBA transcripts. Third, the reciprocal expression was observed in GBA and miR22-3p versus GBAP1 transcripts before and after HL60-induced macrophage differentiation. Nevertheless, these findings clearly demonstrate novel cell-type-specific GBA gene expression regulatory mechanisms, providing new insights into GCase biology.