Public attitudes in Japan toward the reproductive use of gametes derived from human-induced pluripotent stem cells

ヒトiPS細胞を用いた配偶子の作製と利用をめぐる日本の一般市民を対象にした調査. 京都大学プレスリリース. 2021-10-25.[Purpose:] To investigate the interests of the Japanese general public in the reproductive use of in vitro derived (IVD)-gametes. [Methods:] We conducted an online survey and obtained answers from 3096 respondents. [Results:] More than half of the respondents agreed with the reproductive use of IVD-gametes by infertile heterosexual married couples but disagreed with the same use by unmarried or homosexual individuals. Nearly 70.0% disagreed with the use for designing a baby. [Discussion:] In Japan at present, the use of IVD-gametes that deviate from societal values regarding reproduction and family prescribed by the conventional marriage system is unlikely to be accepted. It is also unlikely to be accepted for non-treatment purposes in reproduction

Genome editing of human embryos for research purposes: Japanese lay and expert attitudes

ヒトを対象としたゲノム編集の利用に関する調査研究. 京都大学公式プレスリリース. 2023-09-27.Capturing the lay public's opinions on genome editing of human embryos. 京都大学プレスリリース. 2023-10-12.Background: Multiple surveys of the general public and experts on human genome editing have been conducted. However, many focused only on editing in clinical applications, with few regarding its use for basic research. Given that genome editing for research purposes is indispensable for the realization of clinical genome editing, understanding lay attitudes toward genome editing in research, particularly using human embryos, which is likely to provoke ethical concerns, is helpful for future societal discussion. Methods: An online survey was conducted with Japanese laypeople and researchers to ascertain their views regarding human genome editing for research purposes. Participants were queried about their acceptance as a function of the target of genome editing (germ cells, surplus IVF embryos, research embryos, somatic cells); then, those who answered “acceptable depending on the purpose” were asked about their acceptance in the context of specific research purposes of genome editing. Participants were also asked about their expectations and concerns regarding human genome editing. Results: Replies were obtained from 4, 424 laypeople and 98 researchers. Approximately 28.2–36.9% of the laypeople exhibited strong resistance to genome editing for research purposes regardless of their applications. In contrast, 25.5% of the researchers demonstrated resistance only to genome editing in research embryos; this percentage was substantially higher than those concerning the other three targets (5.1–9.2%). Approximately 50.4–63.4% of laypeople who answered “acceptable depending on the purpose” approved germline genome editing for disease research; however, only 39.3–42.8% approved genome editing in basic research to obtain biological knowledge. In contrast, the researchers displayed a lower degree of acceptance of germline genome editing for research purposes related to chronic diseases (60.9–66.7%) than for other research purposes (73.6–90.8%). Analysis of responses concerning expectations and concerns indicated that laypeople who would not accept genome editing of human embryos did not necessarily worry about “instrumentalization of the embryo.” They also had substantially low expectations for recognized advantages of genome editing, including “advances in science” and “reduction of intractable diseases, ” compared with other groups of respondents. Conclusion: The assumptions shared among experts in conventional bioethical debates and policy discussions on human genome editing are not self-evident to laypeople

Public attitudes in Japan toward the creation and use of gametes derived from human-induced pluripotent stem cells

ヒトiPS細胞を用いた配偶子の作製と利用をめぐる日本の一般市民を対象にした調査. 京都大学プレスリリース. 2021-10-25.[Aim:] To ascertain to what extent the Japanese general public accept the creation and use of in vitro derived (IVD)-gametes derived from human-induced pluripotent stem cells. [Materials & methods:] We conducted an online survey and obtained answers from 3096 respondents. [Results:] 78.6% of the respondents answered that they would accept the creation and use of IVD-gametes for research purposes, 51.7% answered that they would accept the creation and use of embryos with IVD-gametes for research purposes, and 25.9% answered that they would accept childbirth using embryos with IVD-gametes. [Discussion:] The results that approximately half of the respondents answered that they would accept the creation of embryos with IVD-gametes, which has not been allowed in the current Japanese research guidelines, is astonishing

Human genome editing in clinical applications: Japanese lay and expert attitudes

ヒトを対象としたゲノム編集の利用に関する調査研究. 京都大学公式プレスリリース. 2023-09-27.Capturing the lay public's opinions on genome editing of human embryos. 京都大学プレスリリース. 2023-10-12.Background: The world’s first gene-edited babies, reported by the Chinese scientist He Jiankui, prompted an outcry of criticism and concerns worldwide over the use of genome editing for reproductive purposes. Many countries and academic associations opposed to heritable genome editing (HGE) called for public discussion involving various stakeholders. To hold a discussion of this nature and form a consensus concerning HGE, we must understand under what conditions stakeholders consider HGE acceptable and the reasons for which they deem it unacceptable. Methods: Laypeople and researchers were surveyed in May 2019. They were asked about the degree of their acceptance toward somatic genome editing (SGE) and HGE; those who answered “acceptable depending on the purpose” were queried further regarding their acceptance in the contexts of specific clinical purposes. Results: Responses were obtained from 4, 424 laypeople and 98 researchers. The percentage of respondents choosing each option in attitudes to HGE was, from largest to smallest: “acceptable depending on purpose” (laypeople 49.3%; researchers 56.1%), “not acceptable for any purpose” (laypeople 45.8%; researchers 40.8%), and “acceptable for any purpose” (laypeople 5.0%; researchers 3.1%). In an additional question for those who answered “acceptable depending on the purpose, ” laypeople found the following purposes acceptable: infertility treatment (54.5%), treatment of life-threatening diseases (52.2%), and treatment of debilitating diseases (51.4%). Meanwhile, the degree of acceptance for enhancement purposes was 10.7, 7.9, 6.2, and 5.5% for physical, cognitive, health, and personality enhancements, respectively. In contrast, acceptance among the researchers was 94.5% and 92.7% for the treatment of life-threatening and debilitating diseases, respectively, compared with 69.1% for infertility treatment. Researchers’ acceptance for enhancement purposes was similar to that of the lay participants, with 12.7, 9.1, 10.9, and 5.5% for physical, cognitive, health, and personality enhancement, respectively. Conclusion: In the past, debates regarding the acceptability of human genome editing in clinical applications tend to focus on HGE in many countries. Society will now need to debate the acceptability of both types of human genome editing, HGE and SGE

Tetra­methyl­ammonium dihydrogen phosphate hemihydrate

In the crystal structure of the title compound, C4H12N+·H2PO4 −·0.5H2O, the anions form an infinite hydrogen-bonded chain along the [10] direction. The anion chains are connected by water mol­ecules, which lie on crystallographic twofold rotation axes, through O—H⋯O hydrogen bonds. These hydrogen bonds are almost perpendicular to the other hydrogen bonds which create an assembled structure of anions. In addition, C—H⋯O hydrogen bonds between anions and cations are observed

Medium-term outcomes of a program to upgrade the nursing faculty in Cambodia: A qualitative study

Continuous professional development is important for improving professional competencies, such as cognitive knowledge, technical skills, behaviors, and attitudes. Trainees who complete training programs can have a positive influence on their workplaces. However, it is challenging to establish a process that can facilitate individual learning and help achieve training outcomes in educational and clinical workplaces. In Cambodia, a tumultuous history has played a part in the deficit of adequately prepared nursing faculty. Since the faculty development is vital to ensuring the quality of education, the application of upgraded nursing programs has started in 2011. After the completion of upgraded program, an immediate post-training study was conducted in 2014. Results showed that some faculty members did not accept trainees because they lacked an understanding about nursing concepts. The current study aimed to evaluate the medium-term outcomes of an established program that can improve nursing education and to identify relevant factors in light of the institutional development of educational and clinical facilities in Cambodia. A qualitative study incorporating focus group discussions, key-informant interviews, and teaching document reviews was performed with a thematic analysis using the four-level training evaluation model of Kirkpatrick. Finally, factors influencing outcomes were assessed based on the Bronfenbrenner's ecological system theory. Five themes for behavior and three themes for results were identified as medium-term outcomes from an institutional development aspect. The major enabling factors for the above-mentioned themes were the support of institutional managers, continuous networking among trainees, and supportive national policy. Compared with the immediate post-training study findings, the perceived medium-term outcomes became more strategically focused. Then, the impact of training at a considerably broader scale within the workplace was discussed. The findings highlighted the importance of medium-term program delivery and monitoring if one understands the role played in stimulating outcomes. Moreover, the importance of contextual factors including the influence of managers and policy environment were emphasized

Selective Translation of the Measles Virus Nucleocapsid mRNA by La Protein

Measles, caused by measles virus (MeV) infection, is the leading cause of death in children because of secondary infections attributable to MeV-induced immune suppression. Recently, we have shown that wild-type MeVs induce the suppression of protein synthesis in host cells (referred to as “shutoff”) and that viral mRNAs are preferentially translated under shutoff conditions in infected cells. To determine the mechanism behind the preferential translation of viral mRNA, we focused on the 5′ untranslated region (UTR) of nucleocapsid (N) mRNA. The La/SSB autoantigen (La) was found to specifically bind to an N-5′UTR probe. Recombinant La enhanced the translation of luciferase mRNA containing the N-5′UTR (N-fLuc), and RNA interference of La suppressed N-fLuc translation. Furthermore, recombinant MeV lacking the La-binding motif in the N-5′UTR displayed delayed viral protein synthesis and growth kinetics at an early phase of infection. These results suggest that La induced predominant translation of N mRNA via binding to its 5′UTR under shutoff conditions. This is the first report on a cellular factor that specifically regulates paramyxovirus mRNA translation

A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis and angiogenesis.

Fibroblast growth factor-1 (FGF1) and FGF2 play a critical role in angiogenesis, a formation of new blood vessels from existing blood vessels. Integrins are critically involved in FGF signaling through crosstalk. We previously reported that FGF1 directly binds to integrin αvβ3 and induces FGF receptor-1 (FGFR1)-FGF1-integrin αvβ3 ternary complex. We previously generated an integrin binding defective FGF1 mutant (Arg-50 to Glu, R50E). R50E is defective in inducing ternary complex formation, cell proliferation, and cell migration, and suppresses FGF signaling induced by WT FGF1 (a dominant-negative effect) in vitro. These findings suggest that FGFR and αvβ3 crosstalk through direct integrin binding to FGF, and that R50E acts as an antagonist to FGFR. We studied if R50E suppresses tumorigenesis and angiogenesis. Here we describe that R50E suppressed tumor growth in vivo while WT FGF1 enhanced it using cancer cells that stably express WT FGF1 or R50E. Since R50E did not affect proliferation of cancer cells in vitro, we hypothesized that R50E suppressed tumorigenesis indirectly through suppressing angiogenesis. We thus studied the effect of R50E on angiogenesis in several angiogenesis models. We found that excess R50E suppressed FGF1-induced migration and tube formation of endothelial cells, FGF1-induced angiogenesis in matrigel plug assays, and the outgrowth of cells in aorta ring assays. Excess R50E suppressed FGF1-induced angiogenesis in chick embryo chorioallantoic membrane (CAM) assays. Interestingly, excess R50E suppressed FGF2-induced angiogenesis in CAM assays as well, suggesting that R50E may uniquely suppress signaling from other members of the FGF family. Taken together, our results suggest that R50E suppresses angiogenesis induced by FGF1 or FGF2, and thereby indirectly suppresses tumorigenesis, in addition to its possible direct effect on tumor cell proliferation in vivo. We propose that R50E has potential as an anti-cancer and anti-angiogenesis therapeutic agent ("FGF1 decoy")

Discovery and informing research participants of incidental findings detected in brain magnetic resonance imaging studies : Review and multi‐institutional study

Background: Brain imaging studies using magnetic resonance imaging (MRI ) sometimes reveal incidental findings (IFs) that might be relevant to some of the health issues in research participants. Although professional communities have discussed how to manage these IFs, there is no global consensus on the concrete handling procedures including how to inform participants of IFs. Methods: First, this study reviewed previous studies for the number of IFs discovered in brain imaging studies using MEDLINE. Second, a multi‐institutional study determined the number of IF discoveries and evaluated the method of informing participants at multiple institutions, which participated in a national brain science project in Japan. Results: Both the review and multi‐institutional study showed that IFs with a high urgency level were discovered in 0–2.0% of participants, including healthy volunteers, and that the rate of IF discovery in general was higher in studies conducted in elderly population. Moreover, multi‐institutional study suggested the criteria used to judge whether or not to inform participants of IFs may differ by institution. Conclusions: Our results suggest that in order to ensure informing the participants of high urgency IFs, physicians who are capable of interpreting brain images clinically should review all brain images, and the establishment of a support system is required for brain imaging studies at nonmedical institutions. Since the method of informing participants of IFs might affect their understanding and acceptance of IFs, which are related to managing risks of false “clean bill of health” or psychological impacts of informing IFs, further research focusing on communication of IFs is needed