New discovery of the oldest maize weevils in the world from Jomon potteries, Japan

The maize weevil (_Sitophilus zeamais_) and rice weevil (_Sitophilus oryzae_) are two of the most damaging insects for stored grains, and are characteristic species of ancient Japan. Both species and the granary weevil (_Sitophilus granarius_) are common elsewhere in the world, but the natural distribution of maize and rice weevils is restricted to the Old World^1^. Japanese archaeological records contain a few maize weevil fossils after the Middle Yayoi period (ca. 2000 aBP)^2^. However, since evidence of weevils was discovered as impressions in Jomon potsherds in 2004^3^, many weevil impressions have been found. The oldest is from the Late Jomon (ca. 4000 to 3200 aBP). These findings and other archaeological evidence suggest that the maize weevil invaded Japan from Korea, accompanying the spread of rice cultivation^4^. However, in 2010 we discovered older weevil impressions dating to ca. 9000 aBP. These specimens are the oldest harmful insects discovered from archaeological sites around the world. The new discovery is valuable for future entomological research because such specimens are absent from the fossil record. It is also archaeologically and culturally interesting because this provides evidence of harmful insects living in Jomon villages. However, the new discovery raises the question of what these weevils infested: did cereal cultivation exist 9000 years ago? We have no persuasive answer, but hope one will be provided by future interdisciplinary collaborations among geneticists, entomologists, and archaeologists

Supersaturated state of diazepam injection following dilution with infusion fluid

BackgroundSignificant precipitation produced by the dilution of diazepam (DZP) injection with an infusion fluid is a great concern for the clinical practice. In this study, the precipitation behavior under different conditions was investigated.MethodFor the sample preparation, DZP injections (Horizon injection and Cercine injection) were diluted with various infusion fluids (Saline, 5% glucose infusion fluid and Soldem 3A) at designated dilution ratios ranging from 1× to 40× (5 mg/mL to 0.125 mg/mL). In addition, to measure the solubility of DZP in the samples, the saturated solutions of DZP were prepared. The DZP concentrations in the samples were measured by high-performance liquid chromatography (HPLC). This study also investigated the precipitate using various analytical methods: infrared microscopy, 1H-NMR, differential scanning calorimetry, and powder X-ray deflection.ResultsFirst, the compatibility of injection with infusion fluids was investigated. Significant precipitation occurred at dilution ratios ranging from 2× to 20×. No significant effects of formulations and infusion fluids on the compatibility were observed. The solubility of DZP was then further investigated. The concentration of DZP dissolved in the admixtures was higher than the solubility. This indicated that DZP existed in a supersaturated state in the infusion fluid admixtures. In the next phase of this study, the precipitate was investigated using various analytical methods. Results showed that the precipitate in infusion fluid admixtures was mostly composed of DZP, but also contained small amounts of the ingredients of DZP injection, such as benzoic acid and benzyl alcohol.ConclusionsThis study clarified details of the precipitation occurring after dilution of DZP injection with infusion fluids. It is worth noting that DZP in an infusion admixture existed in a supersaturated state. These findings offer important insight into the clinical practice of DZP injection

Methionine Metabolism Regulates Maintenance and Differentiation of Human Pluripotent Stem Cells

SummaryMouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are in a high-flux metabolic state, with a high dependence on threonine catabolism. However, little is known regarding amino acid metabolism in human ESCs/iPSCs. We show that human ESCs/iPSCs require high amounts of methionine (Met) and express high levels of enzymes involved in Met metabolism. Met deprivation results in a rapid decrease in intracellular S-adenosylmethionine (SAM), triggering the activation of p53-p38 signaling, reducing NANOG expression, and poising human iPSC/ESCs for differentiation, follow by potentiated differentiation into all three germ layers. However, when exposed to prolonged Met deprivation, the cells undergo apoptosis. We also show that human ESCs/iPSCs have regulatory systems to maintain constant intracellular Met and SAM levels. Our findings show that SAM is a key regulator for maintaining undifferentiated pluripotent stem cells and regulating their differentiation

A New Light on the Evolution and Propagation of Prehistoric Grain Pests: The World's Oldest Maize Weevils Found in Jomon Potteries, Japan

Three Sitophilus species (S. granarius L., S. oryzae L., and S. zeamais Mots.) are closely related based on DNA analysis of their endosymbionts. All are seed parasites of cereal crops and important economic pest species in stored grain. The Sitophilus species that currently exist, including these three species, are generally believed to be endemic to Asia's forested areas, suggesting that the first infestations of stored grain must have taken place near the forested mountains of southwestern Asia. Previous archaeological data and historical records suggest that the three species may have been diffused by the spread of Neolithic agriculture, but this hypothesis has only been established for granary weevils in European and southwestern Asian archaeological records. There was little archeological evidence for grain pests in East Asia before the discovery of maize weevil impressions in Jomon pottery in 2004 using the “impression replica” method. Our research on Jomon agriculture based on seed and insect impressions in pottery continued to seek additional evidence. In 2010, we discovered older weevil impressions in Jomon pottery dating to ca. 10 500 BP. These specimens are the oldest harmful insects in the world discovered at archaeological sites. Our results provide evidence of harmful insects living in the villages from the Earliest Jomon, when no cereals were cultivated. This suggests we must reconsider previous scenarios for the evolution and propagation of grain pest weevils, especially in eastern Asia. Although details of their biology or the foods they infested remain unclear, we hope future interdisciplinary collaborations among geneticists, entomologists, and archaeologists will provide the missing details

Automatic Network Structure-based Clustering of Multivariate Time Series

本論文では，ネットワーク構造を持つ多次元時系列データのためのパターン検出手法であるNGLについて述べる．NGLは，時間変化するネットワーク構造を持つ多次元時系列データが与えられたときに，その時系列データの中から重要なネットワーク構造を発見し，それらの情報を要約，表現する．具体的に，提案手法は，(a)多次元時系列データからネットワーク構造に基づいた解釈性の高いクラスタを発見する．(b)その際に最適な分割点とクラスタ数を自動的に決定する．すなわち，事前情報の付与が必要ない．そして，(c)自動決定アルゴリズムにより高精度なクラスタリングを実現する．人工データを用いた精度評価実験では最新の既存手法と比較して提案手法が大幅な精度向上を達成していることを明らかにした．また，実データを用いた実験ではNGLが解釈性の高いクラスタを発見していることを確認した．In this paper we present NGL, pattern mining algorithm for multiple time series data with underlying network structures. Our method has the following properties: (a) Interpretable: it provides interpretable network structures for the data; (b) Automatic: it determines the optimal cut points and the number of clusters automatically; (c) Accurate: it provides reliable clustering performance thanks to the automated algorithm. We evaluate our NGL algorithm on synthetic datasets, outperforming state-of-the-art baselines in terms of accuracy. And extensive experiments on real datasets demonstrate that NGL does indeed obtain interpretable network structure clusters

Role of the node in controlling traffic of cadmium, zinc, and manganese in rice

Heavy metals are transported to rice grains via the phloem. In rice nodes, the diffuse vascular bundles (DVBs), which enclose the enlarged elliptical vascular bundles (EVBs), are connected to the panicle and have a morphological feature that facilitates xylem-to-phloem transfer. To find a mechanism for restricting cadmium (Cd) transport into grains, the distribution of Cd, zinc (Zn), manganese (Mn), and sulphur (S) around the vascular bundles in node I (the node beneath the panicle) of Oryza sativa ‘Koshihikari’ were compared 1 week after heading. Elemental maps of Cd, Zn, Mn, and S in the vascular bundles of node I were obtained by synchrotron micro-X-ray fluorescence spectrometry and electron probe microanalysis. In addition, Cd K-edge microfocused X-ray absorption near-edge structure analyses were used to identify the elements co-ordinated with Cd. Both Cd and S were mainly distributed in the xylem of the EVB and in the parenchyma cell bridge (PCB) surrounding the EVB. Zn accumulated in the PCB, and Mn accumulated around the protoxylem of the EVB. Cd was co-ordinated mainly with S in the xylem of the EVB, but with both S and O in the phloem of the EVB and in the PCB. The EVB in the node retarded horizontal transport of Cd toward the DVB. By contrast, Zn was first stored in the PCB and then efficiently transferred toward the DVB. Our results provide evidence that transport of Cd, Zn, and Mn is differentially controlled in rice nodes, where vascular bundles are functionally interconnected

ザイタク キョジャク オヨビ ヨウ カイゴ コウレイシャ ニ オケル カイゴドベツ シンタイ キノウ ノ ケントウ

The purpose of this research is to examine body functions in a regional weak living and the nursing necessary senior citizen and the relations to the nursing necessary level. [Subject]:A regional weak living and needed nursing 167 senior citizens were targeted. [Method]:The object person was analyzed, and the crowd division was done according to the nursing level, and the relation between body functions and the nursing level was analyzed. [Result]: The nursing level decreases the capacity of balance, the lower limbs muscular power, the whole body endurance, and the ambulatory ability and the ability has decreased with advancing. However, the relation to the nursing level was not admitted as for the arm muscular power and flexibility. [Conclusion]: It was suggested that it was necessary to make the best use of this result for the programs aimed at preventing elderly people requiring nursing care from further losing physical and mental strength

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target