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

Superconductivity in undoped T' cuprates with Tc over 30 K

Undoped cuprates have long been considered to be antiferromagnetic insulators. In this article, however, we report that superconductivity is achieved in undoped T'-RE2CuO4 (RE = Pr, Nd, Sm, Eu, and Gd). Our discovery was performed by using metal-organic decomposition (MOD), an inexpensive and easy-to-implement thin-film process. The keys to prepare the superconducting films are firing with low partial-pressure of oxygen and reduction at low temperatures. The highest Tc of undoped T'-RE2CuO4 is over 30 K, substantially higher than "electron-doped" analogs. Remarkably, Gd2CuO4, even the derivatives of which have not shown superconductivity so far, gets superconducting with Tconset as high as ~ 20 K. The implication of our discovery is briefly discussed.Comment: 22 pages, 5 figures, submitted to Physical Review Letter

Fundamental Parameters of the Milky Way Galaxy Based on VLBI astrometry

We present analyses to determine the fundamental parameters of the Galaxy based on VLBI astrometry of 52 Galactic maser sources obtained with VERA, VLBA and EVN. We model the Galaxy's structure with a set of parameters including the Galaxy center distance R_0, the angular rotation velocity at the LSR Omega_0, mean peculiar motion of the sources with respect to Galactic rotation (U_src, V_src, W_src), rotation-curve shape index, and the V component of the Solar peculiar motions V_sun. Based on a Markov chain Monte Carlo method, we find that the Galaxy center distance is constrained at a 5% level to be R_0 = 8.05 +/- 0.45 kpc, where the error bar includes both statistical and systematic errors. We also find that the two components of the source peculiar motion U_src and W_src are fairly small compared to the Galactic rotation velocity, being U_src = 1.0 +/- 1.5 km/s and W_src = -1.4 +/- 1.2 km/s. Also, the rotation curve shape is found to be basically flat between Galacto-centric radii of 4 and 13 kpc. On the other hand, we find a linear relation between V_src and V_sun as V_src = V_sun -19 (+/- 2) km/s, suggesting that the value of V_src is fully dependent on the adopted value of V_sun. Regarding the rotation speed in the vicinity of the Sun, we also find a strong correlation between Omega_0 and V_sun. We find that the angular velocity of the Sun, Omega_sun, which is defined as Omega_sun = Omega_0 + V_sun/R_0, can be well constrained with the best estimate of Omega_sun = 31.09 +/- 0.78 km/s/kpc. This corresponds to Theta_0 = 238 +/- 14 km/s if one adopts the above value of R_0 and recent determination of V_sun ~ 12 km/s.Comment: 14 pages, 6 figures, PASJ in pres

Clinicopathological features of advanced gastric cancer discovered after Helicobacter pylori eradication

　Helicobacter pylori infection is closely associated with gastric cancer, and its eradication is expected to prevent gastric cancer. However, gastric cancer is often detected discovered after eradication therapy for H. pylori infection. We aimed to investigate the endoscopic and clinical features of advanced gastric cancer after H. pylori eradication.　We retrospectively investigated tumor location, macroscopic and histological type, endoscopic gastric mucosal atrophy (using the Kimura-Takemoto classification), and the interval between eradication and detection of gastric cancer.　Nine patients (five males; mean age, 65.3 years [range, 44-79 years]), histologically diagnosed with advanced gastric cancer after successful H. pylori eradication between April 2003 and December 2018, were enrolled in this study.　In all cases, the cancer was located in the middle-to-upper portion of the stomach. With respect to macroscopic type, six cases were ulcerative, two were scirrhous, and one was polypoid. Histologically, all cancers were poorly or moderately differentiated adenocarcinomas. Endoscopic mucosal atrophy was mild in two cases, moderate in two cases, and severe in five cases. Two cases of scirrhous tumors developed from mild mucosal atrophy. Moreover, the tumor was detected within 36 months after H. pylori eradication in six patients (maximum: 120 months, mean: 38.7 months).　Our data demonstrated that post-eradicated advanced gastric cancers were located in the middle-to-upper portion of the stomach and were mainly ulcerative, poorly or moderately differentiated adenocarcinoma. More than half of the patients exhibited severe mucosal atrophy

A case of synchronous triple cancer of the esophagus, stomach, and colon detected by using gastrointestinal screening endoscopy

　In recent years, the detected number of multiple primary malignant tumors (MPMTs) in the gastrointestinal tract has been increasing with the advancement of gastrointestinal endoscopic equipment and the spread of endoscopic screening.　Here, we report a case of synchronous MPMTs of the esophagus, stomach, and colon detected by means of gastrointestinal screening endoscopy. The patient was a 67-year-old man who regularly visited the medical clinic for hypertension. He had a history of alcohol consumption (sake index: 250, with alcohol flushing syndrome) and smoking (Brinkman index: 800), and a family history of cancer (his father had gastric cancer).　At the medical clinic, he underwent gastrointestinal endoscopy for screening purposes. Prior observation with linked-color imaging (LCI), a type of image-enhanced endoscopy (IEE), revealed an irregular depressed lesion in the mid-esophagus. Simultaneously, an irregular, highly deformed depressed lesion and a small depressed lesion were detected on the incisura of the lesser curvature and the lesser curvature of the antrum, respectively. The esophageal lesion was identified as squamous cell carcinoma and both gastric lesions were identified as well-differentiated adenocarcinoma.　The patient was referred to our hospital for further examination and treatment for esophageal and gastric cancer. Subsequent colonoscopy revealed a well-defined, ulcerative tumor in the transverse colon. First, endoscopic submucosal dissection was performed for the esophageal lesion, followed by laparoscopy-assisted distal gastrectomy with D1+ lymph-node dissection and transverse colectomy with D2 lymph-node dissection for the gastric and colorectal lesions, respectively. Histopathologically, the main gastric and colonic tumors were in advanced stages; fortunately, the esophageal cancer was an early-stage lesion (7 × 5 mm, 0-IIc, pT1a-LPM, INFa, ly0, v0, pCurA), which has a much better prognosis than advanced esophageal cancer.　In patients with multiple cancer risk factors (alcohol consumption, smoking, and family history), it is important to consider the possibility of MPMTs. Furthermore, upper gastrointestinal observation combined with IEE, such as LCI, may be useful in the early detection of lesions

Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction

新たなイントラクライン機構を用いた加齢性眼疾患治療へ --眼局所のホルモンの加齢変化とサーカディアンリズムが鍵--. 京都大学プレスリリース. 2022-02-14.Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3β-hydroxyl-steroid dehydrogenase (3β-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3β-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3β-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3β-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction

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

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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

Volume Overload and Pressure Overload due to Left-to-Right Shunt-Induced Myocardial Injury: Evaluation Using a Highly Sensitive Cardiac Troponin-I Assay in Children With Congenital Heart Disease (左-右短絡による容量負荷と圧負荷により誘発される心筋障害-高感度心臓トロポニン-I測定を利用した先天性心疾患小児の評価)

雑誌掲載版心臓トロポニンI(cTnI)急性冠症候群や急性心筋梗塞における最も感度と特異度が高い生物標識である。本研究では、小児の心房中隔欠損症(ASD)30例、心室中隔欠損症(VSD)32例と健康小児350例の血清cTnIを測定した。血清cTnIはASD及びVSDの小児では健康小児より有意に高値で(それぞれP<0.05、P<0.01)、VSD小児では血清cTnIは心カテーテル法で測定した肺動脈血/全身動脈圧比と有意の相関があった(r=0.745、P<0.001