Development of an integrated and inferenceable RDF database of glycan, pathogen and disease resources.

Glycans are known to play extremely important roles in infections by viruses and pathogens. In fact, the SARS-CoV-2 virus has been shown to have evolved due to a single change in glycosylation. However, data resources on glycans, pathogens and diseases are not well organized. To accurately obtain such information from these various resources, we have constructed a foundation for discovering glycan and virus interaction data using Semantic Web technologies to be able to semantically integrate such heterogeneous data. Here, we created an ontology to encapsulate the semantics of virus-glycan interactions, and used Resource Description Framework (RDF) to represent the data we obtained from non-RDF related databases and data associated with literature. These databases include PubChem, SugarBind, and PSICQUIC, which made it possible to refer to other RDF resources such as UniProt and GlyTouCan. We made these data publicly available as open data and provided a service that allows anyone to freely perform searches using SPARQL. In addition, the RDF resources created in this study are available at the GlyCosmos Portal.

DEVELOPMENT OF A ROBOT FOR THE MEASUREMENT OF RADIOACTIVE CONTAMINATION AND FERTILITY OF THE SOIL IN FARMLAND.

A tractor-based robot with the capability of real-time assessing and visualizing the radioactive material density and fertility distribution of farmlands has been developed to accelerate the recovery process of the farmlands suffered by the accident of the Fukushima Daiichi Nuclear Power Plant (FDNPP). In a field test at a decontaminated farmland near FDNPP, within-field heterogeneities of soil contamination and fertility are clarified almost in real-time. Results obtained by this robot are consistent with the map by the conventional soil sampling or the history of decontamination activities.

Discovery of remogliflozin etabonate: A potent and highly selective SGLT2 inhibitor.

We optimized the structure of an active metabolite (1) of WAY-123783, which was obtained from mouse urine after oral administration, to improve selectivity for SGLT2 and oral bioavailability. O-glucoside derivative 24 (remogliflozin etabonate) was subsequently identified as a potent, highly selective, and orally available SGLT2 inhibitor.

Functional modulation of liver mitochondria in lipopolysaccharide/drug co-treated rat liver injury model.

Drug-induced liver injury is not readily detectable using conventional animal studies during pre-clinical drug development. To address this problem, other researchers have proposed the use of co-administration of lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, and a drug. Using this approach, liver injury that is otherwise not detected following drug administration alone can be successfully identified. Previous studies have demonstrated that such injury is suppressed by heparin; therefore, the mechanism may involve coagulation-dependent ischemia. However, it has not been established how LPS-induced ischemia might sensitize hepatocytes to a potentially hepatotoxic drug. In the present study, we aimed to determine the effect of LPS-induced ischemia on liver mitochondrial function and downstream toxicologic responses. Consistent with previous findings, plasma alanine transaminase (ALT) activity was higher in rats co-administered with LPS (1 mg/kg) and diclofenac (100 mg/kg), but reduced by heparin. Liver mRNA expression of Hmox1, encoding heme oxygenase-1, an oxidative stress indicator, was three times higher at 2 hr after LPS administration. Furthermore, respiratory activity via mitochondrial complex II, lipid peroxidation in mitochondria, and the susceptibility to mitochondrial permeability transition pore opening in response to diclofenac administration were significantly increased by LPS administration. The increase in plasma ALT activity and the sensitization to mitochondrial permeability transition pore opening were reduced by the co-administration of heparin. In conclusion, LPS-induced transient ischemia disrupts respiratory chain complex activities, enhances reactive oxygen species production, especially in mitochondria, and sensitizes mitochondria to permeability transition pore opening when testing a potentially hepatotoxic drug in vivo.

[Relation between psychological development and respiratory management in patients with congenital central hypoventilation syndrome in Japan].

OBJECTIVE: To evaluate the psychological development of patients with congenital central hypoventilation syndrome (CCHS). METHODS: We performed a questionnaire-based survey of 17 patients with CCHS aged over 7 years and assessed their clinical course, respiratory management, and psychological development. RESULTS: CCHS was present at birth in 15 patients, of which eight presented with respiratory failure with a low Apgar score. Twelve patients required mechanical ventilation with intubation, and five received mask ventilation. All patients with intubation underwent tracheostomy between 1 and 12 months of age (median 5.5 months), and most of them had associated conditions such as Hirschsprung disease. Four of 12 patients with intubation were eventually switched to mask ventilation and one to diaphragm pacing and mask ventilation. The patients undergoing mask ventilation had relatively milder disease severity and had fewer complications than did the patients with intubation. The psychological development of patients who received tracheostomy ranged from normal to severe retardation. Retardation was more likely to be severe in patients who received tracheostomy in late infancy. All patients who received mask ventilation experienced borderline to moderate psychological retardation. This effect could be attributed to poor compliance with mask fitting. CONCLUSION: Our findings suggest that the psychological development of CCHS patients was influenced by hypoxia; tracheostomy and strict respiratory management since the neonatal period were needed for neurological protection.