1: Transcription of MERVL retrotransposons is required for preimplantation embryo development.
Science of the Month - June 2023
Nature Genetics.
2023, volume 615 ; 127–133 (2023)doi:10.1038
Sakashita A, Kitano T, Ishizu H, Guo YJ, Masuda H, Ariura M, Murano K, Siomi H.
Endogenous retroviruses (ERVs), a type of transposable element, are remnants of exogenous retroviral infections integrated into the host genome during evolution. They are endogenous mutagens that cause genomic mutations through repeated transposition. While ERVs are suppressed in somatic cells, transient high expression of various ERVs is observed during the early stages of development after fertilization. The murine ERV, MERVL, is specifically highly expressed in totipotent 2-cell stage embryos, suggesting its involvement in totipotency, but its functional significance has remained unclear. Although about 1,000 copies of MERVL exist in the genome, we used our originally developed multi-copy gene analysis technology to reveal that suppressing MERVL expression in early embryos causes developmental abnormalities in preimplantation embryos. This is the first report to show that ERV expression is essential for early embryonic development in mammals.
(Haruhiko Siomi, Department of Molecular Biology, equivalent to the 61st graduating class)
2: Dynamics of AMPA receptors regulate epileptogenesis in patients with epilepsy
Tsuyoshi Eiro, Tomoyuki Miyazaki, Mai Hatano, Waki Nakajima, Tetsu Arisawa, Yuuki Takada, Kimito Kimura, Akane Sano, Kotaro Nakano, Takahiro Mihara, Yutaro Takayama, Naoki Ikegaya, Masaki Iwasaki, Akitoyo Hishimoto, Yoshihiro Noda, Takahiro Miyazaki, Hiroyuki Uchida, Hideaki Tani, Nobuhiro Nagai, Teruki Koizumi, Shinichiro Nakajima, Masaru Mimura, Nozomu Matsuda, Kazuaki Kanai, Kazuhiro Takahashi, Hiroshi Ito, Yoji Hirano, Yuichi Kimura, Riki Matsumoto, Akio Ikeda, Takuya Takahashi
A research group led by Professor Takuya Takahashi of the Department of Physiology, Yokohama City University Graduate School of Medicine, has elucidated that the dynamics of AMPA receptors regulate brain function in patients with epilepsy. They used [11C]K-2, a PET tracer developed by the same group (Miyazaki et al. Nature Medicine 2020), which is the world's first technology capable of visualizing and quantifying excitatory glutamate AMPA receptors—a core molecule responsible for brain function—in the living human brain. The trafficking of AMPA receptors to and from synapses is known as a molecular mechanism of plasticity in excitatory glutamate synapses. This study found that while the accumulation of AMPA receptors at synapses due to Hebbian plasticity generates abnormal epileptic brain waves, the removal of AMPA receptors from normally functioning synapses occurs due to homeostatic plasticity, which is associated with increased excitability in the epileptic brain. These findings reveal that two completely different dynamics of AMPA receptors occur simultaneously in the brains of patients with epilepsy, bringing us closer to elucidating the biological mechanisms of epileptogenesis.
(Takuya Takahashi, Department of Physiology, Yokohama City University Graduate School of Medicine, 74th Graduating Class)
3: Sex Difference in Outcomes of Acute Myocardial Infarction in Young Patients.
J Am Coll Cardiol.
2023 May 9;81(18):1797-1806. doi: 10.1016/j.jacc.2023.03.383. PMID: 37137590.
Sawano M, Lu Y, Caraballo C, Mahajan S, Dreyer R, Lichtman JH, D'Onofrio G, Spatz E, Khera R, Onuma O, Murugiah K, Spertus JA, Krumholz HM.
It is rare for young women to have a myocardial infarction compared to men of the same age and older adults. However, once they experience a myocardial infarction, young women are reported to have a two to three times higher in-hospital mortality rate and a higher probability of readmission after discharge compared to men of the same age. This study aimed to clarify sex differences in the causes and timing of readmission within one year after discharge for young patients with myocardial infarction. The VIRGO (meaning Virgo) registry is a multicenter prospective cohort study targeting only young myocardial infarction patients at 103 sites across the United States. It is an observational study led by Professor Harlan Krumholz of CORE at Yale University, the author's host institution. The study included 2,979 patients and considered more than 30 background factors. The results revealed sex differences in readmissions related to coronary arteries and those due to non-cardiac diseases, with the largest sex difference observed in readmissions for non-cardiac diseases. I am greatly honored that this valuable report emphasizes the need for treatment and follow-up that consider sex differences.
(Mitsuaki Sawano, Department of Cardiology, 87th Graduating Class)