Prediction of pharmacological activities from chemical structures with graph convolutional neural networks

化合物の薬理作用を予測する技術を開発 --薬理作用ビッグデータを用いて--. 京都大学プレスリリース. 2021-01-13.Many therapeutic drugs are compounds that can be represented by simple chemical structures, which contain important determinants of affinity at the site of action. Recently, graph convolutional neural network (GCN) models have exhibited excellent results in classifying the activity of such compounds. For models that make quantitative predictions of activity, more complex information has been utilized, such as the three-dimensional structures of compounds and the amino acid sequences of their respective target proteins. As another approach, we hypothesized that if sufficient experimental data were available and there were enough nodes in hidden layers, a simple compound representation would quantitatively predict activity with satisfactory accuracy. In this study, we report that GCN models constructed solely from the two-dimensional structural information of compounds demonstrated a high degree of activity predictability against 127 diverse targets from the ChEMBL database. Using the information entropy as a metric, we also show that the structural diversity had less effect on the prediction performance. Finally, we report that virtual screening using the constructed model identified a new serotonin transporter inhibitor with activity comparable to that of a marketed drug in vitro and exhibited antidepressant effects in behavioural studies

潜水センサスを用いた瀬戸内海倉橋島における浅海魚類相 : 出現魚種の季節的消長 <原著論文>

瀬戸内海の倉橋島において，潜水センサスによる魚類相の周年調査を行った。本調査により，8目29科53種の魚類を確認した。これらは周年定住種16種，季節的定住種37種に分けられた。近年，瀬戸内海で報告されている暖海性魚類と思われる種は確認されなかった。月毎の出現魚種数は，9・10月の41種が最多であり，1・2月の18種が最少であった。冬期には，9・10月に認められた多くの季節的定住種はその姿を消し，周年定住種を中心とした魚類群集が形成された。本調査海域の冬期の最低水温は10℃であり，低水温が種数の変動に影響し，暖海性魚類の出現を制限する要因になっていると考えられた。We conducted a year-long underwater census to survey fish fauna on a reef off Kurahashi Island in the Seto Inland Sea. A total of 53 species (8 orders, 29 families) were recorded; 16 species were residents, 37 were seasonal residents. No tropical/warm-temperate fish were confirmed. The total number of fish species (41) peaked in September and October, but drastically decreased to just 18 species in January and February because of the disappearance of most seasonal residents. These seasonal residents appeared to be prevented from continuing residence in the central part of the Seto Inland Sea because of the low water temperature in winter.※誤植訂正のためPDF差し替え(2018年3月20日

Astrometry of Galactic Star Forming Region Sharpless 269 with VERA : Parallax Measurements and Constraint on Outer Rotation Curve

We have performed high-precision astrometry of H2O maser sources in Galactic star forming region Sharpless 269 (S269) with VERA. We have successfully detected a trigonometric parallax of 189+/-8 micro-arcsec, corresponding to the source distance of 5.28 +0.24/-0.22 kpc. This is the smallest parallax ever measured, and the first one detected beyond 5 kpc. The source distance as well as proper motions are used to constrain the outer rotation curve of the Galaxy, demonstrating that the difference of rotation velocities at the Sun and at S269 (which is 13.1 kpc away from the Galaxy's center) is less than 3%. This gives the strongest constraint on the flatness of the outer rotation curve and provides a direct confirmation on the existence of large amount of dark matter in the Galaxy's outer disk.Comment: 7 pages and 4 figures, Accepted by PASJ (Vol. 59, No. 5, October 25, 2007 issue

Distance to Orion KL Measured with VERA

We present the initial results of multi-epoch VLBI observations of the 22 GHz H2O masers in the Orion KL region with VERA (VLBI Exploration of Radio Astrometry). With the VERA dual-beam receiving system, we have carried out phase-referencing VLBI astrometry and successfully detected an annual parallax of Orion KL to be 2.29+/-0.10 mas, corresponding to the distance of 437+/-19 pc from the Sun. The distance to Orion KL is determined for the first time with the annual parallax method in these observations. Although this value is consistent with that of the previously reported, 480+/-80 pc, which is estimated from the statistical parallax method using proper motions and radial velocities of the H2O maser features, our new results provide the much more accurate value with an uncertainty of only 4%. In addition to the annual parallax, we have detected an absolute proper motion of the maser feature, suggesting an outflow motion powered by the radio source I along with the systematic motion of source I itself.Comment: 7 pages, 3 figures. PASJ, in press (Vol. 59, No. 5, October 25, 2007 issue

A 6-Year Controlled Gastric Adenocarcinoma Metastasized to the Lung, Cervical Spine and Mandible in a Japanese Male: A Patient Report

Gastric adenocarcinoma metastasized to the lung, cervical vertebrae and mandible 6 years after gastrectomy in a 70-year-old man. When the man visited our clinic, he complained of pain in the left mandible with paralysis in the left lower lip and diffuse swelling with a fluctuation inside the left ramus of the mandible. Medium contrast computed tomography (CT) presented bone loss that looked like a wormhole at the left angle of the mandible. Magnetic resonance imaging (MRI) revealed abscess or osteomyelitis at the site. He showed no response despite treatment with antibiotics, and we suspected a neoplastic lesion. With a mandibular ramus specimen obtained by biopsy and examined histopathologically, adenocarcinoma of the salivary gland was strongly suspected. MRI presented a neoplastic lesion in his cervical vertebrae, and by biopsy he was diagnosed with adenocarcinoma. Thereafter, chest CT presented multiple pulmonary metastases. Considering the patient’s history of gastrectomy due to gastric adenocarcinoma, the stomach, cervical vertebrae or mandible were examined pathologically and immunohistochemically by biopsy: all specimens showed a moderately differentiated type of tubular adenocarcinoma, and the results for cytokeratin-related tumor markers were the same. We finally diagnosed him as having metastases from gastric adenocarcinoma to the lung, cervical vertebrae and mandible. Because the metastases had spread to multiple organs, the mandibular lesion was not treated, and terminal care in another facility was unavoidably selected. In making a differential diagnosis of multiple metastases, pathological and immunohistochemical examinations of metastatic lesions by biopsy were very useful based on the diagnostic imagings by CT and MRI

Absolute Proper Motions of H2O Masers Away from the Galactic Plane Measured with VERA in the "Superbubble" Region NGC 281

We report on absolute proper-motion measurements of an H2O maser source in the NGC 281 West molecular cloud, which is located ~320 pc above the Galactic plane and is associated with an HI loop extending from the Galactic plane. We have conducted multi-epoch phase-referencing observations of the maser source with VERA (VLBI Exploration of Radio Astrometry) over a monitoring period of 6 months since May 2006. We find that the H2O maser features in NGC 281 West are systematically moving toward the southwest and further away from the Galactic plane with a vertical velocity of ~20-30 km/s at its estimated distance of 2.2-3.5 kpc. Our new results provide the most direct evidence that the gas in the NGC 281 region on the HI loop was blown out from the Galactic plane, most likely in a superbubble driven by multiple or sequential supernova explosions in the Galactic plane.Comment: 10 pages, 5 figures, PASJ in press (Vol. 59, No. 4; August 25, 2007 issue

Fish Fauna on Reefs of Tokara Islands, Southern Japan, Surveyed By Underwater Census During 2002-2007

トカラ列島口之島，中之島，平島，小宝島の浅海リーフにおいて潜水センサスによる魚類相調査を実施した。2002－2007年にかけて，3名から6名の調査者による約1時間の潜水調査を各島3－5回実施し，総計304魚種を記録した。それらのほぼすべてがサンゴ礁域および琉球列島への分布が報告されている熱帯性魚種であり，亜熱帯水域としての生物地理学的位置づけを強く支持するものであった。80％を越える魚種は，より北方の黒潮流域にある屋久島，高知県柏島からも記録されているものであったが，ヒレグロイットウダイ，ホシニセスズメ，ユカタイシモチ，オキナワサンゴアマダイ，ハマクマノミ，ヤシャベラ，コブブダイ，ゴイシギンポ，カタボシサンカクハゼ，ゴマアイゴ，トサカハギの11種については両地点で記録されておらず，トカラ列島水域を北限とする分布特性を有する可能性が示唆された。We conducted underwater census to survey the fish fauna on reefs of Tokara Islands with aids of the research vessel Toyoshio-maru of Hiroshima University. A total 304 fish species were recorded, and were almost completely comprised of coral reef fishes mainly distributing in the tropical or subtropical waters. This result strongly suggests that Tokara Islands biogeographically belong to the subtropical-water area as a part of the Ryukyu Islands district as ever been proposed by Nakabo (2002a). Through comparisons of the present fish records with data of further northern areas in Kuroshio Current zone, a total of 11 species, Neoniphon opercularis (Holocentridae), Pseudochromis marshallensis (Pseudochromidae), Apogon exostigma (Apogonidae), Hoplolatilus cuniculus (Malacanthidae), Amphiprion frenatus (Pomacentridae), Cheilinus fasciatus (Labridae), Chlorurus oedema (Scaridae), Ecsenius oculus (Blenniidae), Fusigobius humeralis (Gobiidae), Siganus guttatus (Siganidae), Naso tuberosus (Acanthuridae) are suggested to distribute up to Tokara Islands as northern range limits

Physical features of spondylolysis patients

The purpose of this study was to evaluate the physical features of pediatric patients with lumbar spondylolysis (LS), factors that increase the load during compensatory movements at the lumbar spine, and the outcomes of rehabilitation. Twenty patients were included. Fifteen items were used : fingertip-to-floor distance (FFD), straight leg raising (SLR), heel-to-buttock distance (HBD), tightness of the rectus femoris, the lateral and medial rotator muscles, iliopsoas, tensor fascia lata, adductor muscles, soleus muscle, and latissimus dorsi, and trunk rotation, sit-ups and endurance of the abdominal and back muscles. Initial findings were judged as positive or negative using previously reported cut-off values and were re-evaluated 2 or 3 months later. Positive tests were found for HBD and tightness of the rectus femoris in 85% of the patients, for endurance of the abdominal muscles in 75%, SLR and sit-ups in 70%, and FFD and tightness of the external rotator muscles in 60%. The physical features varied according to the type of sport played, and some patients were refractory to rehabilitation. Only 17.6%, 33.3%, and 40.0% of patients with initially positive findings for HBD, tightness of the external rotator muscles, and endurance of the abdominal muscles, respectively, achieved improvements after rehabilitation