Biology subjects

Furukawa, R.

Publications and source records attributed to Furukawa, R..

4 recordsLinked to original sources

bioRxiv2023

Dose-response relationship for the resistance of human insulin to degradation by insulin-degrading enzyme

Deeper understanding of the mechanism of the action of insulin and insulin-degrading enzyme (IDE) is a central theme in research into physiology and the pathophysiology of type 2 diabetes mellitus. Despite significant progress regarding the substrate recruitment, unfolding, digestion, and release by IDE, the structure and function of the insulin hexamer during the degradation cycle of IDE remain to be fully characterized. In the present study, we have characterized the behavior of human insulin hexamer in the absence of zinc. Using cryo-electron microscopy, we also observed that these hexamers represented a structure similar to that of T6 insulin. More interestingly, we also observed complexes in which some of their monomeric insulin components are partially distorted at their hexametric symmetry. This ensures that insulin determines the kinetics of its degradation by IDE without the requirement for zinc. These findings provide new information regarding the molecular events in insulin assembly and disassembly that permit its selective digestion by IDE.

biochemistry↗

bioRxiv2022

Antiviral effect of candies containing persimmon-derived tannin against SARS-CoV-2 delta strain

Inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the mouth has the potential to reduce the spread of coronavirus disease 2019 (COVID-19) because the virus is readily transmitted by dispersed saliva. Persimmon-derived tannin has strong antioxidant and antimicrobial activity owing to its strong adhesiveness to proteins, and it also exhibited antiviral effects against non-variant and alpha variant SARS-CoV-2 in our previous study. In this report, we first demonstrated the antiviral effects of persimmon-derived tannin against the delta variant of SARS-CoV-2 in vitro via the plaque assay method. We then examined the effects of candy containing persimmon-derived tannin. Our plaque assay results show that saliva samples provided by healthy volunteers while they were eating tannin-containing candy remarkably suppressed the virus titers of the SARS-CoV-2 delta variant. In addition, we found that the SARS-CoV-2 viral load in saliva from patients with COVID-19 that was collected immediately after they had eaten the tannin-containing candy was below the level of detection by PCR for SARS-CoV-2. These data suggest that adding persimmon-derived tannin to candy and holding such candy in the mouth is an effective method by which to inactivate the SARS-CoV-2 in saliva, and the application of this approach has potential for inhibiting the transmission of COVID-19.

microbiology↗

bioRxiv2022

Delayed SARS-CoV-2 Spread and Olfactory Cell Lineage Impairment in Close-Contact Infection Syrian Hamster Models

ObjectivesClose contact with patients with COVID-19 is speculated to be the most common cause of viral transmission, but the pathogenesis of COVID-19 by close contact remains to be elucidated. In addition, despite olfactory impairment being a unique complication of COVID-19, the impact of SARS-CoV-2 on the olfactory cell lineage has not been fully validated. This study aimed to elucidate close-contact viral transmission to the nose and lungs and to investigate the temporal damage in the olfactory receptor neuron (ORN) lineage caused by SARS-CoV-2. MethodsSyrian hamsters were orally administered SARS-CoV-2 as direct-infection models. On day 7 after inoculation, infected and uninfected hamsters were housed in the same cage for 30 minutes. These uninfected hamsters were subsequently assigned to a close-contact group. First, viral presence in the nose and lungs was verified in the infection and close-contact groups at several time points. Next, the impacts on the olfactory epithelium, including olfactory progenitors, immature ORNs, and mature ORNs, were examined histologically. Then, the viral transmission status and chronological changes in tissue damage were compared between the direct-infection and close-contact groups. ResultsIn the close-contact group, viral presence could not be detected in both the nose and lungs on day 3, and the virus was identified in both tissues on day 7. In the direct-infection group, the viral load was highest in the nose and lungs on day 3, decreased on day 7, and was no longer detectable on day 14. Histologically, in the direct-infection group, mature ORNs were most depleted on day 3 (p < 0.001) and showed a recovery trend on day 14, with similar trends for olfactory progenitors and immature ORNs. In the close-contact group, there was no obvious tissue damage on day 3, but on day 7, the number of all ORN lineage cells significantly decreased (p < 0.001). ConclusionSARS-CoV-2 was transmitted even after brief contact and subsequent olfactory epithelium and lung damage occurred more than 3 days after the trigger of infection. The present study also indicated that SARS-CoV-2 damages all ORN lineage cells, but this damage can begin to recover approximately 14 days post infection.

microbiology↗

bioRxiv2021

Time-series trend of pandemic SARS-CoV-2 variants visualized using batch-learning self-organizing map for oligonucleotide compositions

To confront the global threat of coronavirus disease 2019, a massive number of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences have been decoded, with the results promptly released through the GISAID database. Based on variant types, eight clades have already been defined in GISAID, but the diversity can be far greater. Owing to the explosive increase in available sequences, it is important to develop new technologies that can easily grasp the whole picture of the big-sequence data and support efficient knowledge discovery. An ability to efficiently clarify the detailed time-series changes in genome-wide mutation patterns will enable us to promptly identify and characterize dangerous variants that rapidly increase their population frequency. Here, we collectively analyzed over 150,000 SARS-CoV-2 genomes to understand their overall features and time-dependent changes using a batch-learning self-organizing map (BLSOM) for oligonucleotide composition, which is an unsupervised machine learning method. BLSOM can separate clades defined by GISAID with high precision, and each clade is subdivided into clusters, which shows a differential increase/decrease pattern based on geographic region and time. This allowed us to identify prevalent strains in each region and to show the commonality and diversity of the prevalent strains. Comprehensive characterization of the oligonucleotide composition of SARS-CoV-2 and elucidation of time-series trends of the population frequency of variants can clarify the viral adaptation processes after invasion into the human population and the time-dependent trend of prevalent epidemic strains across various regions, such as continents.

bioinformatics↗