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

Lifestyle, especially diet, significantly impacts cancer development. Sugimura, T. et al. discovered that grilled fish smoke and charred parts are highly mutagenic in Salmonella typhimurium. They identified two novel mutagenic heterocyclic amines (HCAs), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and its derivative, Trp-P-2, from tryptophan pyrolysate. Published in Proc. Jpn. Acad. (53, 58-61, 1977), their findings initiated the identification of over 10 mutagenic HCAs in cooked foods, most of them newly registered. These 10 HCAs were demonstrated to induce cancers in organs including the liver, colon, breast, and prostate in mice and rats. HCAs are metabolized primarily by CYP1A2 to hydroxyamino derivatives. Their ester forms then adduct at guanine bases, altering genes such as Apc and β-catenin. Quantification of HCAs in cooked foods and human samples, along with epidemiological observations, suggests HCAs likely contribute to human cancers.

Kimura's discovery of z-term in the polar motion (Astron. J. 22, 107 (1902) and Astron. Nachr. 158, 233 (1902)) was recognized as an epoch-making scientific achievement for modern Japan, opening its doors to the world in 1868. Although Kimura served as the chair of the International Latitude Service during 1922-1934 and made efforts to interpret the z-term, it was unsuccessful. The physical interpretation of the z-term was given decades later by Wako (PASJ, 22, 525 (1970)). This article highlights Kimura's additional contributions that led to the interpretation by Wako.

Nonhuman primates, particularly macaque and marmoset monkeys, serve as invaluable models for studying complex brain functions and behavior. However, the lack of suitable genetic neuromodulation tools has constrained research at the network level. This review examines the application of a chemogenetic technology, specifically, designer receptors exclusively activated by designer drugs (DREADDs), to nonhuman primates. DREADDs offer a means of reversibly controlling neuronal activity within a specific cell type or neural pathway, effectively targeting multiple brain regions simultaneously. The combination of DREADDs with imaging techniques, such as positron emission tomography and magnetic resonance imaging, has significantly enhanced nonhuman primate research, facilitating the precise visualization and manipulation of specific brain circuits and enabling the detailed monitoring of changes in network activity, which can then be correlated with altered behavior. This review outlines these technological advances and considers their potential for enhancing our understanding of primate brain circuit function and developing novel therapeutic approaches for treating brain diseases.

In 1929, Matuyama published his paper on the magnetization of mostly Quaternary volcanic rocks. In this paper, he described the results of paleomagnetic measurements of volcanic rocks from Japan and nearby areas and concluded that the latest transition of the magnetic field from reversed to normal state occurred in the early Quaternary. In the 1960s, two groups of scientists from the USA and Australia quite vigorously conducted studies of both magnetization and age of volcanic rocks. By about 1966, they completed the reversal timescale for the last 4 million years, which was to become the basis for many earth science studies. For easy reference, they suggested to call the most recent normal or reversed periods as Brunhes, Matuyama, Gauss, and Gilbert polarity epochs, with the names taken from the scientists who made very important contributions to paleomagnetism. Chron is now the official term for the epoch, and each chron is specified by a combination of a number and a character showing the polarity. However, the names of polarity epochs were already so popular that they are still quite frequently used in scientific papers. The Matuyama epoch is between 0.773 and 2.595 million years before present. Moreover, its lower limit is now used to define the start of the Quaternary.

Regulation of membrane protein integration involves molecular devices such as Sec-translocons or the insertase YidC. We have identified an integration-promoting factor in the inner membrane of Escherichia coli called membrane protein integrase (MPIase). Structural analysis revealed that, despite its enzyme-like name, MPIase is a glycolipid with a long glycan comprising N-acetyl amino sugars, a pyrophosphate linker, and a diacylglycerol (DAG) anchor. Additionally, we found that DAG, a minor membrane component, blocks spontaneous integration. In this review, we demonstrate how they contribute to Sec-independent membrane protein integration in bacteria using a comprehensive approach including synthetic chemistry and biophysical analyses. DAG blocks unfavorable spontaneous integrations by suppressing mobility in the membrane core, whereas MPIase compensates for this. Moreover, MPIase plays critical roles in capturing a substrate protein to prevent its aggregation, attracting it to the membrane surface, facilitating its insertion into the membrane, and delivering it to other factors. The combination of DAG and MPIase efficiently regulates the integration of membrane proteins.

A paper titled "On the Synthesis of Hinokitiol" appeared in this journal in 1950 and marked the beginning of a new research field of novel aromatics.

This review mainly highlights our studies on the synthesis of one-handed helical polymers with a static memory of helicity based on the noncovalent helicity induction with a helical-sense bias and subsequent memory of the helicity approach that we developed during the past decade. Apart from the previous approaches, an excess one-handed helical conformation, once induced by nonracemic molecules, is immediately retained ("memorized") after the complete removal of the nonracemic molecules, accompanied by a significant amplification of the asymmetry, providing novel switchable chiral materials for chromatographic enantioseparation and asymmetric catalysis as well as a highly sensitive colorimetric and fluorescence chiral sensor. A conceptually new one-handed helix formation in a racemic helical polymer composed of racemic repeating units through the deracemization of the pendants is described.

Rikō Majima published seven papers in this journal, and seeing these papers and their surrounding contexts allows us to glance at the birth of a galaxy of scientists.

Biomedical advances of external-beam radiotherapy (EBRT) with improvements in physical accuracy are reviewed. High-precision (±1 mm) three-dimensional radiotherapy (3DRT) can utilize respective therapeutic open doors in the tumor control probability curve and in the normal tissue complication probability curve instead of the one single therapeutic window in two-dimensional EBRT. High-precision 3DRT achieved higher tumor control and probable survival rates for patients with small peripheral lung and liver cancers. Four-dimensional radiotherapy (4DRT), which can reduce uncertainties in 3DRT due to organ motion by real-time (every 0.1-1 s) tumor-tracking and immediate (0.1-1 s) irradiation, have achieved reduced adverse effects for prostate and pancreatic tumors near the digestive tract and with similar or better tumor control. Particle beam therapy improved tumor control and probable survival for patients with large liver tumors. The clinical outcomes of locally advanced or multiple tumors located near serial-type organs can theoretically be improved further by integrating the 4DRT concept with particle beams.

We launched SCRUM-Japan platform for the cancer genome profiling (CGP) test screening followed by the enrollment to genomically-matched clinical trials in 2015. More than 30,000 tissue-based and 10,000 liquid-based CGP tests have already been performed for enrolling to a total of 127 industry-/investigator-initiated registration trials, which resulted in regulatory approvals of 12 new agents with 14 indications in Japan. Using the clinical-genomic database, a new driver gene was recently discovered with dramatic response by genomically-matched agent. Our comparative study with tissue-based CGPs revealed more usefulness of liquid biopsy in terms of less invasive manner, shorter turn-round time, and higher enrollment rate for matched treatments than tissue-based in gastrointestinal cancers. For detecting minimal/molecular residual disease (MRD) after surgery, post-surgical monitoring with tumor-informed liquid biopsy assay in association with two randomized control trials have also started in 2020 (CIRCULATE-Japan). The observational cohort study showed obvious efficacy of the MRD monitoring for predicting recurrence, leading to change clinical practice in patient selection who should receive adjuvant therapy in the near future.