Inflation Targeting and Monetary Policy Activism

We estimate monetary policy activism, defined as responsiveness of the policy interest rate to inflation, among five inflation-targeting countries (the UK, Canada, Sweden, Australia and New Zealand) plus the G3 (the US, Japan and Germany) by applying a time- varying parameter with a stochastic-volatility model. We find that activism of inflation-targeting countries tends to have increased before (not after) the adoption of the inflation-targeting policy framework and that these countries have experienced a decline in activism in recent years, albeit to different degrees. We further explore this result in terms of the constraint of an inflation target range by developing a formal theoretical model in a New Keynesian framework.Inflation-targeting Policy, Monetary Policy Activism, New Keynesian Model, Markov chain Monte Carlo, Time-varying Parameter with Stochastic Volatility Model

Contribution of umami taste substances in human salivation during meal

The oral gustatory perception during a meal has very important physiological roles such as inducing appetite, smoothing mastication and swallowing, promoting digestion and each nutrient availability. One hundred years ago, L-glutamate was discovered as a new taste substance in Japan. Since then, Japanese taste physiologists have lead the research to establish L-glutamate as the prototype molecule for the fifth basic taste (umami taste), in addition to saltiness, sweetness, bitterness and sourness. Meanwhile, various lines of evidence demonstrated that taste perception is linked to taste stimulioral/ pharyngeal reflexes. In this review, we focus on the efficacy of L-glutamate for human salivation and discuss the possible application of umami taste simulation to the nutritional management for the elderly due to amelioration of their quality of life (QOL)

Differential Expression of Vascular Endothelial Growth Factor (VEGF) and VEGF Receptors in the Sequence of Hyperplastic Polyp, Serrated Adenoma and Adenocarcinoma of Colorectum

AIM: The aim of this study was to investigate the role for vascular endothelial growth factor (VEGF) and its receptors, VEGFR-1 and -2, in the hyperplastic polyp (HP)- serrated adenoma (SA)-adenocarcinoma (AC) sequence of the colorectum.Methods: Thirty-six HPs, 33 SAs and 7 ACs (which contained HP and/or SA) were immunohistochemically examined for the expression of VEGF, VEGFR-1, and VEGFR-2.Results: VEGF protein was expressed in the cytoplasm of SA and AC tumor cells, and VEGFR-1 and VEGFR-2 were expressed both in the cytoplasm and on the membrane of these tumors, while there was faint or no expression of VEGF, VEGFR-1 and VEGFR-2 in HPs. Immunohistochemical staining revealed that 8.3% (3 of 36) HPs, 87.9% (29 of 33) SAs and 100% (7 of 7) ACs were positive for VEGF; 2.8% (1 of 36) HPs, 97.0% (32 of 33) SAs and 100% (7 of 7) ACs were positive for VEGFR-1; 16.7% (6 of 36) HPs, 100% (33 of 33) SAs and 100% (7 of 7) ACs were positive for VEGFR-2. The expression of VEGF, VEGFR-1 or VEGFR-2 was statistically correlated with the sequence of HP, SA and AC (P < 0.0001, respectively) Conclusion: Our results suggest that the VEGF pathway may play an important role in the HP-SA-AC sequence

Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1

成人T細胞白血病リンパ腫の多段階発がん分子メカニズムを解明 --難治性疾患の新規治療標的候補を複数同定--. 京都大学プレスリリース. 2021-09-07.Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)–infected cells occurs before viral carcinogenesis. Here we characterize premalignant cells and the multicellular ecosystem in HTLV-1 infection with and without adult T-cell leukemia/lymphoma (ATL) by genome sequencing and single-cell simultaneous transcriptome and T/B-cell receptor sequencing with surface protein analysis. We distinguish malignant phenotypes caused by HTLV-1 infection and leukemogenesis and dissect clonal evolution of malignant cells with different clinical behavior. Within HTLV-1–infected cells, a regulatory T-cell phenotype associates with premalignant clonal expansion. We also delineate differences between virus- and tumor-related changes in the nonmalignant hematopoietic pool, including tumor-specific myeloid propagation. In a newly generated conditional knockout mouse model recapitulating T-cell–restricted CD274 (encoding PD-L1) gene lesions found in ATL, we demonstrate that PD-L1 overexpressed by T cells is transferred to surrounding cells, leading to their PD-L1 upregulation. Our findings provide insights into clonal evolution and immune landscape of multistep virus carcinogenesis

Novel Prophylactic Vaccine Using a Prime-Boost Method and Hemagglutinating Virus of Japan-Envelope against Tuberculosis

Objective. Mycobacterium tuberculosis infection is a major global threat to human health. The only tuberculosis (TB) vaccine currently available is bacillus Calmette-Guérin (BCG), although it has no efficacy in adults. Therefore, the development of a novel vaccine against TB for adults is desired. Method. A novel TB vaccine expressing mycobacterial heat shock protein 65 (HSP65) and interleukin-12 (IL-12) delivered by the hemagglutinating virus of Japan- (HVJ)- envelope was evaluated against TB infection in mice. Bacterial load reductions and histopathological assessments were used to determine efficacy. Results. Vaccination by BCG prime with IgHSP65+murine IL-12/HVJ-envelope boost resulted in significant protective efficacy (>10, 000-fold versus BCG alone) against TB infection in the lungs of mice. In addition to bacterial loads, significant protective efficacy was demonstrated by histopathological analysis of the lungs. Furthermore, the vaccine increased the number of T cells secreting IFN-γ. Conclusion. This vaccine showed extremely significant protection against TB in a mouse model, consistent with results from a similar paper on cynomolgus monkeys. The results suggest that further development of the vaccine for eventual testing in clinical trials may be warranted

Expression and Significance of Angiopoietin-1, 2 and Tie-2 Receptor in Human Extrahepatic Bile Duct Carcinoma: Correlation with Clinicopathological Factors

Extrahepatic bile duct cancer is a high mortal malignancy. Angiopoietin (Ang) and its receptor Tie, which are known to contribute to angiogenesis, have recently been reported to participate in the proliferation and differentiation of malignant tumor cells. The aim of this study is to investigate the expression and the significance of Ang-1, 2 and Tie-2 in extrahepatic bile duct carcinoma cells. We used immunohistochemistry to study 119 cases of surgically resected human extrahepatic bile duct carcinoma, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) to confirm the expression of Ang-1, 2 and Tie-2 mRNA. Among these 119 cases, 52 (43.7%), 50 (42.0%) and 89 (74.8%) cases showed positive staining for Ang-1, 2 and Tie-2, respectively, in bile duct carcinoma cells. In 38 cases of normal mucosa, 6 (15.8%), 10 (26.3%) and 9 (23.7%) cases were positive for Ang-1, 2 and Tie-2, respectively. The positivity for Ang-1 and Tie-2 in normal mucosa was significantly different from all carcinomas (p<0.01 and p<0.001, respectively). We found no significant correlation between Ang-1 and Ang-2 expression and other clinicopathological factors such as histological differentiation, grade of tumor invasion or survival rate after surgery. In contrast, Tie-2 expression correlated significantly with degree of desmoplasia, cancer stage and survival of patients. RT-PCR analyses of five surgically resected tumor samples and three human bile duct cancer cell lines all showed positive expression of Ang-1, 2 and Tie-2 mRNAs. High expressions of Ang-1, 2 and Tie-2 in human extrahepatic bile duct carcinoma cells suggested that Ang-Tie system may be involved in the progression of human bile duct cancer

Variant Spectrum of von Hippel-Lindau Disease and Its Genomic Heterogeneity in Japan

Von Hippel-Lindau (VHL) disease is an autosomal dominant, inherited syndrome with variants in the VHL gene, causing predisposition to multi-organ neoplasms with vessel abnormality. Germline variants in VHL can be detected in 80-90% of patients clinically diagnosed with VHL disease. Here, we summarize the results of genetic tests for 206 Japanese VHL families, and elucidate the molecular mechanisms of VHL disease, especially in variant-negative unsolved cases. Of the 206 families, genetic diagnosis was positive in 175 families (85%), including 134 families (65%) diagnosed by exon sequencing (15 novel variants) and 41 (20%) diagnosed by multiplex ligation-dependent probe amplification (MLPA) (one novel variant). The deleterious variants were significantly enriched in VHL disease Type 1. Interestingly, five synonymous or non-synonymous variants within exon 2 caused exon 2 skipping, which is the first report of exon 2 skipping caused by several missense variants. Whole genome and target deep sequencing analysis were performed for 22 unsolved cases with no variant identified and found three cases with VHL mosaicism (variant allele frequency: 2.5-22%), one with mobile element insertion in the VHL promoter region, and two with a pathogenic variant of BAP1 or SDHB. The variants associated with VHL disease are heterogeneous, and for more accuracy of the genetic diagnosis of VHL disease, comprehensive genome and DNA/RNA analyses are required to detect VHL mosaicism, complicated structure variants and other related gene variants

Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis

Shide, K., Kameda, T., Kamiunten, A. et al. Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis. Blood Cancer J. 9, 42 (2019). https://doi.org/10.1038/s41408-019-0202-