著者

Hideki Kakeya Yoshihisa Matsumoto

出版者

Information Processing Society of Japan

雑誌

IPSJ Transactions on Bioinformatics (ISSN:18826679)

巻号頁・発行日

vol.15, pp.22-29, 2022 (Released:2022-11-16)

参考文献数

35

---

A method to find a probability that a given bias of mutations occur naturally is proposed to test whether a newly detected virus is a product of natural evolution or a product of non-natural process such as genetic manipulation. The probability is calculated based on the neutral theory of molecular evolution and binominal distribution of non-synonymous (N) and synonymous (S) mutations. Though most of the conventional analyses, including dN/dS analysis, assume that any kinds of point mutations from a nucleotide to another nucleotide occurs with the same probability, the proposed model takes into account the bias in mutations, where the equilibrium of mutations is considered to estimate the probability of each mutation. The proposed method is applied to evaluate whether the Omicron variant strain of SARS-CoV-2, whose spike protein includes 29 N mutations and only one S mutation, can emerge through natural evolution. The result of binomial test based on the proposed model shows that the bias of N/S mutations in the Omicron spike can occur with a probability of 2.0 × 10-3 or less. Even with the conventional model where the probabilities of any kinds of mutations are all equal, the strong N/S mutation bias in the Omicron spike can occur with a probability of 3.7 × 10-3, which means that the Omicron variant is highly likely a product of non-natural process including artifact.

著者

Nakashi SASANO Atsushi ENOMOTO Yoshio HOSOI Yosuke KATSUMURA Yoshihisa MATSUMOTO Kenshiro SHIRAISHI Kiyoshi MIYAGAWA Hiroshi IGAKI Keiichi NAKAGAWA

出版者

Journal of Radiation Research Editorial Committee

雑誌

Journal of Radiation Research (ISSN:04493060)

巻号頁・発行日

vol.48, no.6, pp.495-503, 2007 (Released:2007-11-21)

参考文献数

58

被引用文献数

20

---

Edaravone, a clinical drug used widely for the treatment of acute cerebral infarction, is reported to scavenge free radicals. In the present study, we investigated the radioprotective effect of edaravone on X-ray-induced apoptosis in MOLT-4 cells. Apoptosis was determined by the dye exclusion test, Annexin V binding assay, cleavage of caspase, and DNA fragmentation. We found that edaravone significantly suppressed the X-ray-induced apoptosis. The amount of intracellular ROS production was determined by the chloromethyl-2',7'-dichlorodihydro-fluorescein diacetate system. We found that the intracellular ROS production by X-irradiation was completely suppressed by the addition of edaravone. The accumulation and phosphorylation of p53 and the expression of p21WAF1, a target protein of p53, which were induced by X-irradiation, were also suppressed by adding edaravone. We conclude that the free radical scavenger edaravone suppresses X-ray-induced apoptosis in MOLT-4 cells by inhibiting p53.