Biology subjects

Konno, Y.

Publications and source records attributed to Konno, Y..

4 recordsLinked to original sources

bioRxiv2021

Cinnamon bark extract suppresses metastatic dissemination of cancer cells through inhibition of glycolytic metabolism

Metastasis, a leading contributor to the morbidity of cancer patients, occurs through multiple steps. As each of these steps is promoted by different molecular mechanisms, blocking metastasis needs to target each of these steps. Here we report that cinnamon bark extract (CBE) has a suppressor effect on metastatic dissemination of cancer cells. Though a zebrafish embryo screen which utilizes conserved mechanisms between metastasis and zebrafish gastrulation for identifying anti-metastasis drugs, CBE was identified to interfere with gastrulation progression of zebrafish. A zebrafish xenotransplantation model of metastasis validated that CBE suppressed metastatic dissemination of human cancer cells (MDA-MB-231). Interestingly, quantitative metabolome analyses revealed that CBE-treated MDA-MB-231 cells disrupted the production of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P), which are intermediate metabolites of glycolytic metabolism. CBE decreased the expression of hexokinase 2 (HK2), which catalyzes G6P production, and pharmacological inhibition of HK2 suppressed cell invasion and migration of MDA-MB-231 cells. Taken together, CBE suppressed metastatic dissemination of human cancer cells by inhibiting glycolytic metabolism.

pharmacology and toxicology↗

bioRxiv2020

Marker-assisted selection of trees with MALE STERALITY 1 in Cryptomeria japonica D. Don

Practical use of marker-assisted selection (MAS) is limited in conifers because of the difficulty with developing markers due to a rapid decrease in linkage disequilibrium, the limited genomic information available, and the diverse genetic backgrounds among breeding material collections. First, in this study, two families were produced by artificial crossing between two male-sterile trees, Shindai11 and Shindai12, and a plus tree, Suzu-2 (Ms1/ms1) (S11-S and S12-S families, respectively). The segregation ratio between male-sterile and male-fertile trees did not deviate significantly from the expected 1:1 ratio in either family. These results clearly suggested that the male-sterile gene of Shindai11 and Shindai12 is MALE STERALITY 1 (MS1). Because some markers reported previously have not been linkage mapped, we constructed a partial linkage map of the region encompassing MS1 using the S11-S and S12-S families. For the S11-S and S12-S families, 19 and 18 markers were mapped onto the partial linkage maps of MS1 region, respectively. There was collinearity (conserved gene order) between the two partial linkage maps. Two markers (CJt020762_ms1-1 and reCj19250_2335) were mapped to the same position as the MS1 locus on both maps. Of these markers, we used CJt020762 for MAS in this study. According to the MAS results for 650 trees from six prefectures of Japan (603 trees from breeding materials and 47 trees from the Ishinomaki natural population), five trees in Niigata Prefecture and one tree in Yamagata Prefecture had heterozygous ms1-1, and three trees in Miyagi Prefecture had heterozygous ms1-2. The results obtained in this study suggested that there may be geographical hotspots for the ms1-1 and ms1-2 alleles. Because MAS can be used effectively to reduce the labor and time required for selection of trees with a male-sterile gene, the number of breeding materials should increase in the future.

genetics↗

bioRxiv2020

SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant

One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays revealed that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of more than 15,000 SARS-CoV-2 sequences identified a natural variant, in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients, but also describe a possibility of the emergence of natural SARS-CoV-2 quasispecies with extended ORF3b that may exacerbate COVID-19 symptoms. HighlightsO_LIORF3b of SARS-CoV-2 and related bat and pangolin viruses is a potent IFN antagonist C_LIO_LISARS-CoV-2 ORF3b suppresses IFN induction more efficiently than SARS-CoV ortholog C_LIO_LIThe anti-IFN activity of ORF3b depends on the length of its C-terminus C_LIO_LIAn ORF3b with increased IFN antagonism was isolated from two severe COVID-19 cases C_LI

microbiology↗

bioRxiv2018

Gorilla APOBEC3 restricts SIVcpz and influences lentiviral evolution in great ape cross-species transmissions

Restriction factors including APOBEC3 family proteins have the potential prevent cross-species lentivirus transmissions. Such events as well as ensuing pathogenesis require the viral Vif protein to overcome/neutralize/degrade the APOBEC3 enzymes of the new host species. Previous investigations have focused on the molecular interaction between human APOBEC3s and HIV-1 Vif. However, the evolutionary interplay between lentiviruses and great ape (including human, chimpanzee and gorilla) APOBEC3s has not been fully investigated. Here we demonstrate that gorilla APOBEC3G plays a pivotal role in restricting lentiviral transmission from chimpanzee to gorilla. We also reveal that a sole amino acid substitution in Vif is sufficient to overcome the gorilla APOBEC3G-mediated species barrier. Moreover, the antiviral effects of gorilla APOBEC3D and APOBEC3F are considerably weaker than those of human and chimpanzee counterparts, which can result in the skewed evolution of great ape lentiviruses leading to HIV-1.\n\nHighlightsO_LISIVcpz requires M16E mutation in Vif to counteract gorilla A3G\nC_LIO_LIAcidic residue at position 16 of Vif is crucial to counteract gorilla A3G\nC_LIO_LIGorilla A3D and A3F poorly suppress lentiviral infectivity\nC_LIO_LISIVgor and related HIV-1s counteract human A3D and A3F independently of DRMR motif\nC_LI

microbiology↗