Is epigenome editing non-inheritable? Implications for ethics and the regulation of human applications

科学の最新動向を基に、エピゲノム編集の倫理・規制を議論. 京都大学プレスリリース. 2023-11-03.Potential inheritable effects and ethical considerations of epigenome editing. 京都大学プレスリリース. 2023-11-03.Epigenome editing offers ethical advantages with non-inheritable gene expression control. However, concerns arise regarding potential transgenerational effects in humans. Ethical and regulatory evaluation is crucial, considering recent advancements and enhanced understanding of transgenerational epigenetics in both mammals and humans

Multiscale expansion of the lattice potential KdV equation on functions of infinite slow-varyness order

We present a discrete multiscale expansion of the lattice potential Korteweg-de Vries (lpKdV) equation on functions of infinite order of slow-varyness. To do so we introduce a formal expansion of the shift operator on many lattices holding at all orders. The lowest secularity condition from the expansion of the lpKdV equation gives a nonlinear lattice equation, depending on shifts of all orders, of the form of the nonlinear Schr\"odinger (NLS) equationComment: 9 pages, submitted to Journ. Phys.

Vestigial-like 2 contributes to normal muscle fiber type distribution in mice

Honda, M., Hidaka, K., Fukada, Si. et al. Vestigial-like 2 contributes to normal muscle fiber type distribution in mice. Sci Rep 7, 7168 (2017). https://doi.org/10.1038/s41598-017-07149-

Differentiation of human embryonic stem cells and human induced pluripotent stem cells into steroid-producing cells.

Although there have been reports of the differentiation of mesenchymal stem cells and mouse embryonic stem (ES) cells into steroid-producing cells, the differentiation of human ES/induced pluripotent stem (iPS) cells into steroid-producing cells has not been reported. The purpose of our present study was to establish a method for inducing differentiation of human ES/iPS cells into steroid-producing cells. The first approach we tried was embryoid body formation and further culture on adherent plates. The resultant differentiated cells expressed mRNA encoding the steroidogenic enzymes steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, cytochrome P450-containing enzyme (CYP)-11A1, CYP17A1, and CYP19, and secreted progesterone was detected in the cell medium. However, expression of human chorionic gonadotropin was also detected, suggesting the differentiated cells were trophoblast like. We next tried a multistep approach. As a first step, human ES/iPS cells were induced to differentiate into the mesodermal lineage. After 7 d of differentiation induced by 6-bromoindirubin-3'-oxime (a glycogen synthase kinase-3β inhibitor), the human ES/iPS cells had differentiated into fetal liver kinase-1- and platelet derived growth factor receptor-α-expressing mesodermal lineage cells. As a second step, plasmid DNA encoding steroidogenic factor-1, a master regulator of steroidogenesis, was introduced into these mesodermal cells. The forced expression of steroidogenic factor-1 and subsequent addition of 8-bromoadenosine 3',5'-cyclic monophosphate induced the mesodermal cells to differentiate into the steroidogenic cell lineage, and expression of CYP21A2 and CYP11B1, in addition to steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, CYP11A1, and CYP17A1, was detected. Moreover, secreted cortisol was detected in the medium, but human chorionic gonadotropin was not. These findings indicate that the steroid-producing cells obtained through the described multistep method are not trophoblast like; instead, they exhibit characteristics of adrenal cortical cells

Characterization of an active LINE-1 in the naked mole-rat genome.

Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-living rodent species. A reason for their long lifespan is pronounced cancer resistance. Therefore, researchers believe that NMRs have unknown secrets of cancer resistance and seek to find them. Here, to reveal the secrets, we noticed a retrotransposon, long interspersed nuclear element 1 (L1). L1s can amplify themselves and are considered endogenous oncogenic mutagens. Since the NMR genome contains fewer L1-derived sequences than other mammalian genomes, we reasoned that the retrotransposition activity of L1s in the NMR genome is lower than those in other mammalian genomes. In this study, we successfully cloned an intact L1 from the NMR genome and named it NMR-L1. An L1 retrotransposition assay using the NMR-L1 reporter revealed that NMR-L1 was active retrotransposon, but its activity was lower than that of human and mouse L1s. Despite lower retrotrasposition activity, NMR-L1 was still capable of inducing cell senescence, a tumor-protective system. NMR-L1 required the 3' untranslated region (UTR) for retrotransposition, suggesting that NMR-L1 is a stringent-type of L1. We also confirmed the 5' UTR promoter activity of NMR-L1. Finally, we identified the G-quadruplex structure of the 3' UTR, which modulated the retrotransposition activity of NMR-L1. Taken together, the data indicate that NMR-L1 retrotranspose less efficiently, which may contribute to the cancer resistance of NMRs

Paediatric HIV and elimination of mother-to-child transmission of HIV in the ASEAN region: a call to action

Recent achievements in scaling up paediatric antiretroviral therapy (ART) have changed the life of children living with HIV, who now stay healthy and live longer lives. However, as it becomes more of a chronic infection, a range of new problems have begun to arise. These include the disclosure of HIV serostatus to children, adherence to ART, long-term toxicities of antiretroviral drugs and their sexual and reproductive health, which are posing significant challenges to the existing health systems caring for children with HIV with limited resources, experiences and capacities. While intensified efforts and actions to improve care and treatment for these children are needed, it is crucial to accelerate the prevention of mother-to-child transmission (PMTCT) of HIV, which is the main cause of paediatric HIV in the ASEAN region so as to eliminate the fundamental cause of the problem. This report argues that given over 70% of women have access to at least one antenatal care visit in the region and acceptance of HIV testing after receiving counselling on PMTCT could be as high as 90%, there is an opportunity to strengthen PMTCT services and eventually eliminate new paediatric HIV infections in the ASEAN countries