Proceedings of the Japan Academy. Series B, Physical and Biological Sciences最新文献

N-Glycanase 1 (NGLY1) deficiency is a congenital disorder caused by mutations in the NGLY1 gene. Because systemic Ngly1^-/- mice with a C57BL/6 (B6) background are embryonically lethal, studies on the mechanism of NGLY1 deficiency using mice have been problematic. In this study, B6-Ngly1^-/+ mice were crossed with Japanese wild mice-originated Japanese fancy mouse 1 (JF1) mice to produce viable F₂ Ngly1^-/- mice from (JF1×B6)F₁ Ngly1^-/+ mice. Systemic Ngly1^-/- mice with a JF1 mouse background were also embryonically lethal. Hybrid F1 Ngly1^-/- (JF1/B6F1) mice, however, showed developmental delay and motor dysfunction, similar to that in human patients. JF1/B6F1 Ngly1^-/- mice showed increased levels of plasma and urinary aspartylglycosamine, a potential biomarker for NGLY1 deficiency. JF1/B6F1 Ngly1^-/- mice are a useful isogenic animal model for the preclinical testing of therapeutic options and understanding the precise pathogenic mechanisms responsible for NGLY1 deficiency.

This paper describes the development and present status of seismic evaluation and seismic retrofit of existing buildings mainly for low-rise and medium-rise reinforced concrete buildings in Japan. First, since the seismic evaluation of existing buildings has close relationships with the seismic design of new buildings, a brief history of the development of seismic design, seismic evaluation, and seismic retrofit is provided in terms of major earthquake disasters mostly in Japan and associated with some major events in the U.S. Then, the development of seismic evaluation and retrofit is reviewed, focusing on the items in which the author has been deeply involved. This provides insight into previous earthquake damage, methodologies for seismic evaluation, the basic concept of the Standard for Seismic Evaluation of Existing Reinforced Concrete Buildings, studies on the demand criteria for seismic safety, and the present status of seismic evaluation and retrofit. Finally, the typical methods of seismic retrofit and some examples of retrofitted buildings in Japan are explained.

Hydrangea (Hydrangea macrophylla) is a unique flower because it is composed of sepals rather than true petals that have the ability to change color. In the early 20th century, it was known that soil acidity and Al³⁺ content could intensify the blue hue of the sepals. In the mid-20th century, the anthocyanin component 3-O-glucosyldelphinidin (1) and the copigment components 5-O-caffeoylquinic, 5-O-p-coumaroylquinic, and 3-O-caffeoylquinic acids (2-4) were reported. Interestingly, all hydrangea colors from red to purple to blue are produced by the same organic components. We were interested in this phenomenon and the chemical mechanisms underlying hydrangea color variation. In this review, we summarize our recent studies on the chemical mechanisms underlying hydrangea sepal color development, including the structure of the blue complex, transporters involved in accumulation of aluminum ion (Al³⁺), and distribution of the blue complex and aluminum ions in living sepal tissue.

Ubiquitination is a reversible post-translational modification in which ubiquitin chains are conjugated to target proteins to modulate protein function. The type of ubiquitin chain determines the mode of protein regulation. It has been shown that ubiquitin chains are formed via one of seven Lys residues in ubiquitin, and several types of ubiquitin chains are found in cells. We identified a new type of linear ubiquitin chain linked through the N-terminal Met of ubiquitin and assembled by the linear ubiquitin chain assembly complex (LUBAC), which is specific for linear chains. The discovery of linear ubiquitin chains and LUBAC is considered as a paradigm shift in ubiquitin research because linear ubiquitination is exclusive to animals, despite the existence of ubiquitination throughout eukaryotic kingdoms. Linear ubiquitination plays a critical role in immune signaling and cell death regulation. Dysregulation of LUBAC-mediated linear ubiquitination underlies various human diseases, including autoinflammation, autoimmunity, infection, and malignant tumors. This review summarizes the current status of linear ubiquitination research.

We examined the development of gastric cancer risk screening, from rat pepsinogen studies in an experimental rat gastric carcinogenesis model induced with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and human pepsinogen studies in the 1970s and 1980s to the recent "ABC method" for human gastric cancer risk screening. First, decreased expression or absence of a major pepsinogen isozyme, PG1, was observed in the rat gastric mucosa from the early stages of gastric carcinogenesis to adenocarcinomas following treatment with MNNG. In the 1980s, decreases in PGI in the human gastric mucosa and serum were identified as markers of atrophic gastritis. In the 1990s, other researchers revealed that chronic infection with Helicobacter pylori (Hp) causes atrophic gastritis and later gastric cancer. In the 2000s, a gastric cancer risk screening method combining assays to detect serum anti-Hp IgG antibody and serum PGI and PGII levels, the "ABC method", was established. Eradication of Hp and endoscopic follow-up examination after the ABC method are recommended to prevent gastric cancer.

We continue (Ref. 1: Proc. Jpn. Acad. Ser. B 97, 22-49) to analyze the COVID-19 status. We concentrate on the following issues in this work:1. Effect of vaccination against the spreading of SARS-CoV-2.2. General landscape of the world situation concerning vaccinations.3. Some aspects of the new variants of SARS-CoV-2.Our findings include:1. With vaccinations, it is fair to say that we have entered a new phase in the fight against the virus SARS-CoV-2. We have analyzed some preliminary data to find how vaccinations can be effective against COVID-19 spreading. This analysis is based on, and is a continuation of, our first paper quoted in Ref. 1.2. If Tokyo (or Japan) continues to keep its vaccination schedule (starting in early April, 2021 and finishing it for elderly, 65 or older, in 4 months), it will see a sign of control of the virus in early June, 2021 although we see changes of this status due to new, more contagious variants.3. The strength (parameter β) of a new contagious variant can be estimated based on the initial data on the variant (Section 5).

The interconversion between spin, charge, and heat currents is being actively studied from the viewpoints of both fundamental physics and thermoelectric applications in the field of spin caloritronics. This field is a branch of spintronics, which has developed rapidly since the discovery of the thermo-spin conversion phenomenon called the spin Seebeck effect. In spin caloritronics, various thermo-spin conversion phenomena and principles have subsequently been discovered and magneto-thermoelectric effects, thermoelectric effects unique to magnetic materials, have received renewed attention with the advances in physical understanding and thermal/thermoelectric measurement techniques. However, the existence of various thermo-spin and magneto-thermoelectric conversion phenomena with similar names may confuse non-specialists. Thus, in this Review, the basic behaviors, spin-charge-heat current conversion symmetries, and functionalities of spin-caloritronic phenomena are summarized, which will help new entrants to learn fundamental physics, materials science, and application studies in spin caloritronics.

Research on lipid peroxidation in food degradation, oil and fat nutrition, and age-related diseases has gained significant international attention for the view of improvement of societal health and longevity. In order to promote basic studies on these topics, a chemiluminescence detection-high performance liquid chromatography instrument using a high-sensitivity single photon counter as a detector was developed. This instrument enabled us to selectively detect and quantify lipid hydroperoxides, a primary product of lipid peroxidation reactions, as hydroperoxide groups at the lipid class level. Furthermore, an analytical method using liquid chromatography-tandem mass spectrometry has been established to discriminate the position and stereoisomerization of hydroperoxide groups in lipid hydroperoxides. Using these two methods, the reaction mechanisms of lipid peroxidation in food and in the body have been confirmed.

As we look so different, our genomic sequences vary enormously. The differences in our genome, genetic variations, have played very significant roles in medical research and have contributed to improvement of medical managements in the last 2-3 decades. Genetic variations include germline variations, somatic mutations, and diversities in receptor genes of rearranged immune cells, T cells and B cells. Germline variants are in some cases causative of genetic diseases, are associated with the risk of various diseases, and also affect drug efficacies or adverse events. Some somatic mutations are causative of tumor development. Recent DNA sequencing technologies allow us to perform single-cell analysis or detailed repertoire analysis of B and T cells. It is critically important to investigate temporal changes in immune environment in various anatomical regions in the next one to two decades. In this review article, we would like to introduce the roles of genetic variations in medical fields in the past, at present and in the future.